U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C25H30N6O2
Molecular Weight 446.5456
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ERDAFITINIB

SMILES

CC(C)NCCN(c1ccc2c(c1)nc(cn2)-c3cnn(C)c3)c4cc(cc(c4)OC)OC

InChI

InChIKey=OLAHOMJCDNXHFI-UHFFFAOYSA-N
InChI=1S/C25H30N6O2/c1-17(2)26-8-9-31(20-10-21(32-4)13-22(11-20)33-5)19-6-7-23-24(12-19)29-25(15-27-23)18-14-28-30(3)16-18/h6-7,10-17,26H,8-9H2,1-5H3

HIDE SMILES / InChI

Molecular Formula C25H30N6O2
Molecular Weight 446.5456
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Erdafitinib (JNJ-42756493) is a potent and selective orally bioavailable, pan fibroblast growth factor receptor (FGFR) inhibitor with potential antineoplastic activity. It was discovered in collaboration with Janssen Pharmaceutica, N.V. from a partnership which commenced in June 2008. Astex’s FGFr inhibitor program originated from a collaboration initiated in 2005 with the Cancer Research UK Drug Discovery Group at the Newcastle Cancer Centre (Newcastle University UK), and Cancer Research Technology Limited. JNJ42756493 is currently being evaluated by Janssen in Phase 2 clinical trials in patients with urothelial cancer, advanced hepatocellular carcinoma, advanced non-small lung cancer, esophageal cancer or cholangiocarcinoma. JNJ-42756493 is a potent, oral pan-FGFR tyrosine kinase inhibitor with half-maximal inhibitory concentration values in the low nanomolar range for all members of the FGFR family (FGFR1 to FGFR4), with minimal activity on vascular endothelial growth factor receptor (VEGFR) kinases compared with FGFR kinases (approximately 20-fold potency difference). In vitro, the proliferation of cells treated with JNJ-42756493 is decreased, associated with increased apoptotic death and decreased cell survival. It is also in phase I trials for the treatment of advanced refractory solid tumors or advanced refractory hematologic cancer.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1399 ng/mL
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ERDAFITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
29268 ng × h/mL
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ERDAFITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
59 h
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ERDAFITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
8 mg 1 times / day steady-state, oral
dose: 8 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ERDAFITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12 mg 1 times / day multiple, oral
Highest studied dose
dose: 12 mg 1 times / day
route: oral
experiment_type: multiple
dose_type: Highest studied dose
co-adm with
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/28965185/
    unhealthy, 62.7 years
    population: unhealthy
    age: 62.7 years
    sex: M+F
    food_status:
    n:
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/28965185/
    DLT: Retinal pigment epithelium atrophy...
    Dose limiting toxicities:
    Retinal pigment epithelium atrophy (grade 21 times / day)

    data_source:
    https://pubmed.ncbi.nlm.nih.gov/28965185/
    10 mg 1 times / day multiple, oral
    RP2D
    dose: 10 mg 1 times / day
    route: oral
    experiment_type: multiple
    dose_type: RP2D
    co-adm with
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/28965185/
      unhealthy, 65.7 years
      population: unhealthy
      age: 65.7 years
      sex: M+F
      food_status:
      n:
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/28965185/
      Other AEs: Hyperphosphatemia...
      Other AEs:
      Hyperphosphatemia (1 times / day)

      data_source:
      https://pubmed.ncbi.nlm.nih.gov/28965185/
      12 mg 1 times / day multiple, oral
      Highest studied dose
      dose: 12 mg 1 times / day
      route: oral
      experiment_type: multiple
      dose_type: Highest studied dose
      co-adm with
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/26324363/
        unhealthy, adult
        population: unhealthy
        age: adult
        sex: unknown
        food_status:
        n:
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/26324363/
        DLT: Alanine aminotransferase increase...
        Dose limiting toxicities:
        Alanine aminotransferase increase (grade 31 times / day)

        data_source:
        https://pubmed.ncbi.nlm.nih.gov/26324363/
        12 mg 1 times / day steady, oral
        Highest studied dose
        dose: 12 mg 1 times / day
        route: oral
        experiment_type: steady
        dose_type: Highest studied dose
        co-adm with
          data_source:
          https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212018Orig1s000MultidisciplineR.pdf
          unhealthy, adult
          population: unhealthy
          age: adult
          sex: unknown
          food_status:
          n:
          data_source:
          https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212018Orig1s000MultidisciplineR.pdf
          8 mg 1 times / day steady, oral
          Recommended
          dose: 8 mg 1 times / day
          route: oral
          experiment_type: steady
          dose_type: Recommended
          co-adm with
            data_source:
            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
            unhealthy, adult
            population: unhealthy
            age: adult
            sex: unknown
            food_status:
            n:
            data_source:
            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
            Disc. AE: Acute myocardial infarction, Eye disorders...
            Other AEs: Hyperphosphatemia, Stomatitis...
            AEs leading to
            discontinuation/dose reduction:​
            Acute myocardial infarction (grade 51 times / day)
            Eye disorders (1 times / day)

            Other AEs:
            Hyperphosphatemia (1 times / day)
            Stomatitis (1 times / day)
            Eye disorders (1 times / day)
            Palmar-plantar erythrodysaesthesia syndrome (1 times / day)
            Eye disorders (1 times / day)
            Stomatitis (1 times / day)
            Hyperphosphatemia (1 times / day)
            Palmar-plantar erythrodysaesthesia syndrome (1 times / day)
            Paronychia (1 times / day)
            Nail dystrophy (1 times / day)

            data_source:
            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
            8 mg 1 times / day steady, oral
            Recommended
            dose: 8 mg 1 times / day
            route: oral
            experiment_type: steady
            dose_type: Recommended
            co-adm with
              data_source:
              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
              unhealthy, adult
              population: unhealthy
              age: adult
              sex: unknown
              food_status:
              n:
              data_source:
              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
              Other AEs: Hemoglobin decreased, Platelets decreased...
              Other AEs:
              Hemoglobin decreased (grade 3-41 times / day)
              Platelets decreased (grade 3-41 times / day)
              Neutrophil count decreased (grade 3-41 times / day)
              Phosphate increased (grade 3-41 times / day)
              Creatinine increased (grade 3-41 times / day)
              Sodium decreased (grade 3-41 times / day)
              Alanine aminotransferase increased (grade 3-41 times / day)
              Alkaline phosphatase increased (grade 3-41 times / day)
              Magnesium decreased (grade 3-41 times / day)
              Phosphate decreased (grade 3-41 times / day)
              Calcium increased (grade 3-41 times / day)

              data_source:
              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
              8 mg 1 times / day steady, oral
              Recommended
              dose: 8 mg 1 times / day
              route: oral
              experiment_type: steady
              dose_type: Recommended
              co-adm with
                data_source:
                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                unhealthy, adult
                population: unhealthy
                age: adult
                sex: unknown
                food_status:
                n:
                data_source:
                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                Other AEs: Stomatitis, Diarrhea...
                Other AEs:
                Stomatitis (all grades1 times / day)
                Diarrhea (all grades1 times / day)
                Dry mouth (all grades1 times / day)
                Constipation (all grades1 times / day)
                Abdominal pain (all grades1 times / day)
                Nausea (all grades1 times / day)
                Vomiting (all grades1 times / day)
                Decreased appetite (all grades1 times / day)
                Fatigue (all grades1 times / day)
                Pyrexia (all grades1 times / day)
                Onycholysis (all grades1 times / day)
                Dry skin (all grades1 times / day)
                Palmar-plantar erythrodysaesth. (all grades1 times / day)
                Alopecia (all grades1 times / day)
                Nail discoloration (all grades1 times / day)
                Dry eye (all grades1 times / day)
                Vision blurred (all grades1 times / day)
                Lacrimation increased (all grades1 times / day)
                Dysgeusia (all grades1 times / day)
                Paronychia (all grades1 times / day)
                Urinary tract infection (all grades1 times / day)
                Conjunctivitis (all grades1 times / day)
                Oropharyngeal pain (all grades1 times / day)
                Dyspnea (all grades1 times / day)
                Hematuria (all grades1 times / day)
                Musculoskeletal pain (all grades1 times / day)
                Arthralgia (all grades1 times / day)
                Weight decreased (all grades1 times / day)
                Stomatitis (grade 3-41 times / day)
                Diarrhea (grade 3-41 times / day)
                Constipation (grade 3-41 times / day)
                Abdominal pain (grade 3-41 times / day)
                Nausea (grade 3-41 times / day)
                Vomiting (grade 3-41 times / day)
                Fatigue (grade 3-41 times / day)
                Pyrexia (grade 3-41 times / day)
                Onycholysis (grade 3-41 times / day)
                Palmar-plantar erythrodysaesth. (grade 3-41 times / day)
                Dry eye (grade 3-41 times / day)
                Dysgeusia (grade 3-41 times / day)
                Paronychia (grade 3-41 times / day)
                Urinary tract infection (grade 3-41 times / day)
                Oropharyngeal pain (grade 3-41 times / day)
                Dyspnea (grade 3-41 times / day)
                Hematuria (grade 3-41 times / day)
                Gastrointestinal disorders (all grades1 times / day)
                Metabolism and nutrition disorders (all grades1 times / day)
                Skin and subcutaneous tissue disorders (all grades1 times / day)
                Eye disorders (all grades1 times / day)
                Nervous system disorders (all grades1 times / day)
                Infections and infestations (all grades1 times / day)
                Respiratory, thoracic and mediastinal disorders (all grades1 times / day)
                Renal and urinary disorders (all grades1 times / day)
                Musculoskeletal and connective tissue disorders (all grades1 times / day)
                Gastrointestinal disorders (grade 3-41 times / day)
                Metabolism and nutrition disorders (grade 3-41 times / day)
                Skin and subcutaneous tissue disorders (grade 3-41 times / day)
                Eye disorders (grade 3-41 times / day)
                Nervous system disorders (grade 3-41 times / day)
                Infections and infestations (grade 3-41 times / day)
                Respiratory, thoracic and mediastinal disorders (grade 3-41 times / day)
                Renal and urinary disorders (grade 3-41 times / day)
                Hemoglobin decreased (all grades1 times / day)
                Platelets decreased (all grades1 times / day)
                Leukocyte count decreased (all grades1 times / day)
                Neutrophil count decreased (all grades1 times / day)
                Phosphate increased (all grades1 times / day)
                Creatinine increased (all grades1 times / day)
                Sodium decreased (all grades1 times / day)
                Alanine aminotransferase increased (all grades1 times / day)
                Alkaline phosphatase increased (all grades1 times / day)
                Albumin decreased (all grades1 times / day)
                Aspartate aminotransferase increased (all grades1 times / day)
                Magnesium decreased (all grades1 times / day)
                Phosphate decreased (all grades1 times / day)
                Calcium increased (all grades1 times / day)
                Potassium increased (all grades1 times / day)
                Fasting blood glucose increased (all grades1 times / day)

                data_source:
                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                AEs

                AEs

                AESignificanceDosePopulation
                Hyperphosphatemia 3 pts%
                10 mg 1 times / day multiple, oral
                RP2D
                dose: 10 mg 1 times / day
                route: oral
                experiment_type: multiple
                dose_type: RP2D
                co-adm with
                  data_source:
                  https://pubmed.ncbi.nlm.nih.gov/28965185/
                  unhealthy, 65.7 years
                  population:
                  age:
                  sex:
                  food_status:
                  n:
                  data_source:
                  https://pubmed.ncbi.nlm.nih.gov/28965185/
                  Retinal pigment epithelium atrophy grade 2,1 pts%
                  DLT
                  12 mg 1 times / day multiple, oral
                  Highest studied dose
                  dose: 12 mg 1 times / day
                  route: oral
                  experiment_type: multiple
                  dose_type: Highest studied dose
                  co-adm with
                    data_source:
                    https://pubmed.ncbi.nlm.nih.gov/28965185/
                    unhealthy, 62.7 years
                    population:
                    age:
                    sex:
                    food_status:
                    n:
                    data_source:
                    https://pubmed.ncbi.nlm.nih.gov/28965185/
                    Alanine aminotransferase increase grade 3,1 pts%
                    DLT
                    12 mg 1 times / day multiple, oral
                    Highest studied dose
                    dose: 12 mg 1 times / day
                    route: oral
                    experiment_type: multiple
                    dose_type: Highest studied dose
                    co-adm with
                      data_source:
                      https://pubmed.ncbi.nlm.nih.gov/26324363/
                      unhealthy, adult
                      population:
                      age:
                      sex:
                      food_status:
                      n:
                      data_source:
                      https://pubmed.ncbi.nlm.nih.gov/26324363/
                      Stomatitis 15%
                      8 mg 1 times / day steady, oral
                      Recommended
                      dose: 8 mg 1 times / day
                      route: oral
                      experiment_type: steady
                      dose_type: Recommended
                      co-adm with
                        data_source:
                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                        unhealthy, adult
                        population:
                        age:
                        sex:
                        food_status:
                        n:
                        data_source:
                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                        Eye disorders 17%
                        8 mg 1 times / day steady, oral
                        Recommended
                        dose: 8 mg 1 times / day
                        route: oral
                        experiment_type: steady
                        dose_type: Recommended
                        co-adm with
                          data_source:
                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                          unhealthy, adult
                          population:
                          age:
                          sex:
                          food_status:
                          n:
                          data_source:
                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                          Stomatitis 17%
                          8 mg 1 times / day steady, oral
                          Recommended
                          dose: 8 mg 1 times / day
                          route: oral
                          experiment_type: steady
                          dose_type: Recommended
                          co-adm with
                            data_source:
                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                            unhealthy, adult
                            population:
                            age:
                            sex:
                            food_status:
                            n:
                            data_source:
                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                            Eye disorders 23%
                            8 mg 1 times / day steady, oral
                            Recommended
                            dose: 8 mg 1 times / day
                            route: oral
                            experiment_type: steady
                            dose_type: Recommended
                            co-adm with
                              data_source:
                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                              unhealthy, adult
                              population:
                              age:
                              sex:
                              food_status:
                              n:
                              data_source:
                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                              Hyperphosphatemia 24%
                              8 mg 1 times / day steady, oral
                              Recommended
                              dose: 8 mg 1 times / day
                              route: oral
                              experiment_type: steady
                              dose_type: Recommended
                              co-adm with
                                data_source:
                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                unhealthy, adult
                                population:
                                age:
                                sex:
                                food_status:
                                n:
                                data_source:
                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                Nail dystrophy 6%
                                8 mg 1 times / day steady, oral
                                Recommended
                                dose: 8 mg 1 times / day
                                route: oral
                                experiment_type: steady
                                dose_type: Recommended
                                co-adm with
                                  data_source:
                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                  unhealthy, adult
                                  population:
                                  age:
                                  sex:
                                  food_status:
                                  n:
                                  data_source:
                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                  Eye disorders 6%
                                  Disc. AE
                                  8 mg 1 times / day steady, oral
                                  Recommended
                                  dose: 8 mg 1 times / day
                                  route: oral
                                  experiment_type: steady
                                  dose_type: Recommended
                                  co-adm with
                                    data_source:
                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                    unhealthy, adult
                                    population:
                                    age:
                                    sex:
                                    food_status:
                                    n:
                                    data_source:
                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                    Hyperphosphatemia 7%
                                    8 mg 1 times / day steady, oral
                                    Recommended
                                    dose: 8 mg 1 times / day
                                    route: oral
                                    experiment_type: steady
                                    dose_type: Recommended
                                    co-adm with
                                      data_source:
                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                      unhealthy, adult
                                      population:
                                      age:
                                      sex:
                                      food_status:
                                      n:
                                      data_source:
                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                      Palmar-plantar erythrodysaesthesia syndrome 7%
                                      8 mg 1 times / day steady, oral
                                      Recommended
                                      dose: 8 mg 1 times / day
                                      route: oral
                                      experiment_type: steady
                                      dose_type: Recommended
                                      co-adm with
                                        data_source:
                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                        unhealthy, adult
                                        population:
                                        age:
                                        sex:
                                        food_status:
                                        n:
                                        data_source:
                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                        Paronychia 7%
                                        8 mg 1 times / day steady, oral
                                        Recommended
                                        dose: 8 mg 1 times / day
                                        route: oral
                                        experiment_type: steady
                                        dose_type: Recommended
                                        co-adm with
                                          data_source:
                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                          unhealthy, adult
                                          population:
                                          age:
                                          sex:
                                          food_status:
                                          n:
                                          data_source:
                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                          Palmar-plantar erythrodysaesthesia syndrome 8%
                                          8 mg 1 times / day steady, oral
                                          Recommended
                                          dose: 8 mg 1 times / day
                                          route: oral
                                          experiment_type: steady
                                          dose_type: Recommended
                                          co-adm with
                                            data_source:
                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                            unhealthy, adult
                                            population:
                                            age:
                                            sex:
                                            food_status:
                                            n:
                                            data_source:
                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                            Dyspnea all grades,10%
                                            8 mg 1 times / day steady, oral
                                            Recommended
                                            dose: 8 mg 1 times / day
                                            route: oral
                                            experiment_type: steady
                                            dose_type: Recommended
                                            co-adm with
                                              data_source:
                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                              unhealthy, adult
                                              population:
                                              age:
                                              sex:
                                              food_status:
                                              n:
                                              data_source:
                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                              Fasting blood glucose increased all grades,10%
                                              8 mg 1 times / day steady, oral
                                              Recommended
                                              dose: 8 mg 1 times / day
                                              route: oral
                                              experiment_type: steady
                                              dose_type: Recommended
                                              co-adm with
                                                data_source:
                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                unhealthy, adult
                                                population:
                                                age:
                                                sex:
                                                food_status:
                                                n:
                                                data_source:
                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                Lacrimation increased all grades,10%
                                                8 mg 1 times / day steady, oral
                                                Recommended
                                                dose: 8 mg 1 times / day
                                                route: oral
                                                experiment_type: steady
                                                dose_type: Recommended
                                                co-adm with
                                                  data_source:
                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                  unhealthy, adult
                                                  population:
                                                  age:
                                                  sex:
                                                  food_status:
                                                  n:
                                                  data_source:
                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                  Neutrophil count decreased all grades,10%
                                                  8 mg 1 times / day steady, oral
                                                  Recommended
                                                  dose: 8 mg 1 times / day
                                                  route: oral
                                                  experiment_type: steady
                                                  dose_type: Recommended
                                                  co-adm with
                                                    data_source:
                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                    unhealthy, adult
                                                    population:
                                                    age:
                                                    sex:
                                                    food_status:
                                                    n:
                                                    data_source:
                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                    Arthralgia all grades,11%
                                                    8 mg 1 times / day steady, oral
                                                    Recommended
                                                    dose: 8 mg 1 times / day
                                                    route: oral
                                                    experiment_type: steady
                                                    dose_type: Recommended
                                                    co-adm with
                                                      data_source:
                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                      unhealthy, adult
                                                      population:
                                                      age:
                                                      sex:
                                                      food_status:
                                                      n:
                                                      data_source:
                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                      Conjunctivitis all grades,11%
                                                      8 mg 1 times / day steady, oral
                                                      Recommended
                                                      dose: 8 mg 1 times / day
                                                      route: oral
                                                      experiment_type: steady
                                                      dose_type: Recommended
                                                      co-adm with
                                                        data_source:
                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                        unhealthy, adult
                                                        population:
                                                        age:
                                                        sex:
                                                        food_status:
                                                        n:
                                                        data_source:
                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                        Hematuria all grades,11%
                                                        8 mg 1 times / day steady, oral
                                                        Recommended
                                                        dose: 8 mg 1 times / day
                                                        route: oral
                                                        experiment_type: steady
                                                        dose_type: Recommended
                                                        co-adm with
                                                          data_source:
                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                          unhealthy, adult
                                                          population:
                                                          age:
                                                          sex:
                                                          food_status:
                                                          n:
                                                          data_source:
                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                          Nail discoloration all grades,11%
                                                          8 mg 1 times / day steady, oral
                                                          Recommended
                                                          dose: 8 mg 1 times / day
                                                          route: oral
                                                          experiment_type: steady
                                                          dose_type: Recommended
                                                          co-adm with
                                                            data_source:
                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                            unhealthy, adult
                                                            population:
                                                            age:
                                                            sex:
                                                            food_status:
                                                            n:
                                                            data_source:
                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                            Oropharyngeal pain all grades,11%
                                                            8 mg 1 times / day steady, oral
                                                            Recommended
                                                            dose: 8 mg 1 times / day
                                                            route: oral
                                                            experiment_type: steady
                                                            dose_type: Recommended
                                                            co-adm with
                                                              data_source:
                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                              unhealthy, adult
                                                              population:
                                                              age:
                                                              sex:
                                                              food_status:
                                                              n:
                                                              data_source:
                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                              Vomiting all grades,13%
                                                              8 mg 1 times / day steady, oral
                                                              Recommended
                                                              dose: 8 mg 1 times / day
                                                              route: oral
                                                              experiment_type: steady
                                                              dose_type: Recommended
                                                              co-adm with
                                                                data_source:
                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                unhealthy, adult
                                                                population:
                                                                age:
                                                                sex:
                                                                food_status:
                                                                n:
                                                                data_source:
                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                Pyrexia all grades,14%
                                                                8 mg 1 times / day steady, oral
                                                                Recommended
                                                                dose: 8 mg 1 times / day
                                                                route: oral
                                                                experiment_type: steady
                                                                dose_type: Recommended
                                                                co-adm with
                                                                  data_source:
                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                  unhealthy, adult
                                                                  population:
                                                                  age:
                                                                  sex:
                                                                  food_status:
                                                                  n:
                                                                  data_source:
                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                  Potassium increased all grades,16%
                                                                  8 mg 1 times / day steady, oral
                                                                  Recommended
                                                                  dose: 8 mg 1 times / day
                                                                  route: oral
                                                                  experiment_type: steady
                                                                  dose_type: Recommended
                                                                  co-adm with
                                                                    data_source:
                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                    unhealthy, adult
                                                                    population:
                                                                    age:
                                                                    sex:
                                                                    food_status:
                                                                    n:
                                                                    data_source:
                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                    Weight decreased all grades,16%
                                                                    8 mg 1 times / day steady, oral
                                                                    Recommended
                                                                    dose: 8 mg 1 times / day
                                                                    route: oral
                                                                    experiment_type: steady
                                                                    dose_type: Recommended
                                                                    co-adm with
                                                                      data_source:
                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                      unhealthy, adult
                                                                      population:
                                                                      age:
                                                                      sex:
                                                                      food_status:
                                                                      n:
                                                                      data_source:
                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                      Leukocyte count decreased all grades,17%
                                                                      8 mg 1 times / day steady, oral
                                                                      Recommended
                                                                      dose: 8 mg 1 times / day
                                                                      route: oral
                                                                      experiment_type: steady
                                                                      dose_type: Recommended
                                                                      co-adm with
                                                                        data_source:
                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                        unhealthy, adult
                                                                        population:
                                                                        age:
                                                                        sex:
                                                                        food_status:
                                                                        n:
                                                                        data_source:
                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                        Paronychia all grades,17%
                                                                        8 mg 1 times / day steady, oral
                                                                        Recommended
                                                                        dose: 8 mg 1 times / day
                                                                        route: oral
                                                                        experiment_type: steady
                                                                        dose_type: Recommended
                                                                        co-adm with
                                                                          data_source:
                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                          unhealthy, adult
                                                                          population:
                                                                          age:
                                                                          sex:
                                                                          food_status:
                                                                          n:
                                                                          data_source:
                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                          Urinary tract infection all grades,17%
                                                                          8 mg 1 times / day steady, oral
                                                                          Recommended
                                                                          dose: 8 mg 1 times / day
                                                                          route: oral
                                                                          experiment_type: steady
                                                                          dose_type: Recommended
                                                                          co-adm with
                                                                            data_source:
                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                            unhealthy, adult
                                                                            population:
                                                                            age:
                                                                            sex:
                                                                            food_status:
                                                                            n:
                                                                            data_source:
                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                            Vision blurred all grades,17%
                                                                            8 mg 1 times / day steady, oral
                                                                            Recommended
                                                                            dose: 8 mg 1 times / day
                                                                            route: oral
                                                                            experiment_type: steady
                                                                            dose_type: Recommended
                                                                            co-adm with
                                                                              data_source:
                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                              unhealthy, adult
                                                                              population:
                                                                              age:
                                                                              sex:
                                                                              food_status:
                                                                              n:
                                                                              data_source:
                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                              Platelets decreased all grades,19%
                                                                              8 mg 1 times / day steady, oral
                                                                              Recommended
                                                                              dose: 8 mg 1 times / day
                                                                              route: oral
                                                                              experiment_type: steady
                                                                              dose_type: Recommended
                                                                              co-adm with
                                                                                data_source:
                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                unhealthy, adult
                                                                                population:
                                                                                age:
                                                                                sex:
                                                                                food_status:
                                                                                n:
                                                                                data_source:
                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                Musculoskeletal pain all grades,20%
                                                                                8 mg 1 times / day steady, oral
                                                                                Recommended
                                                                                dose: 8 mg 1 times / day
                                                                                route: oral
                                                                                experiment_type: steady
                                                                                dose_type: Recommended
                                                                                co-adm with
                                                                                  data_source:
                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                  unhealthy, adult
                                                                                  population:
                                                                                  age:
                                                                                  sex:
                                                                                  food_status:
                                                                                  n:
                                                                                  data_source:
                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                  Nausea all grades,21%
                                                                                  8 mg 1 times / day steady, oral
                                                                                  Recommended
                                                                                  dose: 8 mg 1 times / day
                                                                                  route: oral
                                                                                  experiment_type: steady
                                                                                  dose_type: Recommended
                                                                                  co-adm with
                                                                                    data_source:
                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                    unhealthy, adult
                                                                                    population:
                                                                                    age:
                                                                                    sex:
                                                                                    food_status:
                                                                                    n:
                                                                                    data_source:
                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                    Calcium increased all grades,22%
                                                                                    8 mg 1 times / day steady, oral
                                                                                    Recommended
                                                                                    dose: 8 mg 1 times / day
                                                                                    route: oral
                                                                                    experiment_type: steady
                                                                                    dose_type: Recommended
                                                                                    co-adm with
                                                                                      data_source:
                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                      unhealthy, adult
                                                                                      population:
                                                                                      age:
                                                                                      sex:
                                                                                      food_status:
                                                                                      n:
                                                                                      data_source:
                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                      Abdominal pain all grades,23%
                                                                                      8 mg 1 times / day steady, oral
                                                                                      Recommended
                                                                                      dose: 8 mg 1 times / day
                                                                                      route: oral
                                                                                      experiment_type: steady
                                                                                      dose_type: Recommended
                                                                                      co-adm with
                                                                                        data_source:
                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                        unhealthy, adult
                                                                                        population:
                                                                                        age:
                                                                                        sex:
                                                                                        food_status:
                                                                                        n:
                                                                                        data_source:
                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                        Phosphate decreased all grades,24%
                                                                                        8 mg 1 times / day steady, oral
                                                                                        Recommended
                                                                                        dose: 8 mg 1 times / day
                                                                                        route: oral
                                                                                        experiment_type: steady
                                                                                        dose_type: Recommended
                                                                                        co-adm with
                                                                                          data_source:
                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                          unhealthy, adult
                                                                                          population:
                                                                                          age:
                                                                                          sex:
                                                                                          food_status:
                                                                                          n:
                                                                                          data_source:
                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                          Alopecia all grades,26%
                                                                                          8 mg 1 times / day steady, oral
                                                                                          Recommended
                                                                                          dose: 8 mg 1 times / day
                                                                                          route: oral
                                                                                          experiment_type: steady
                                                                                          dose_type: Recommended
                                                                                          co-adm with
                                                                                            data_source:
                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                            unhealthy, adult
                                                                                            population:
                                                                                            age:
                                                                                            sex:
                                                                                            food_status:
                                                                                            n:
                                                                                            data_source:
                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                            Palmar-plantar erythrodysaesth. all grades,26%
                                                                                            8 mg 1 times / day steady, oral
                                                                                            Recommended
                                                                                            dose: 8 mg 1 times / day
                                                                                            route: oral
                                                                                            experiment_type: steady
                                                                                            dose_type: Recommended
                                                                                            co-adm with
                                                                                              data_source:
                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                              unhealthy, adult
                                                                                              population:
                                                                                              age:
                                                                                              sex:
                                                                                              food_status:
                                                                                              n:
                                                                                              data_source:
                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                              Constipation all grades,28%
                                                                                              8 mg 1 times / day steady, oral
                                                                                              Recommended
                                                                                              dose: 8 mg 1 times / day
                                                                                              route: oral
                                                                                              experiment_type: steady
                                                                                              dose_type: Recommended
                                                                                              co-adm with
                                                                                                data_source:
                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                unhealthy, adult
                                                                                                population:
                                                                                                age:
                                                                                                sex:
                                                                                                food_status:
                                                                                                n:
                                                                                                data_source:
                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                Dry eye all grades,28%
                                                                                                8 mg 1 times / day steady, oral
                                                                                                Recommended
                                                                                                dose: 8 mg 1 times / day
                                                                                                route: oral
                                                                                                experiment_type: steady
                                                                                                dose_type: Recommended
                                                                                                co-adm with
                                                                                                  data_source:
                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                  unhealthy, adult
                                                                                                  population:
                                                                                                  age:
                                                                                                  sex:
                                                                                                  food_status:
                                                                                                  n:
                                                                                                  data_source:
                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                  Aspartate aminotransferase increased all grades,30%
                                                                                                  8 mg 1 times / day steady, oral
                                                                                                  Recommended
                                                                                                  dose: 8 mg 1 times / day
                                                                                                  route: oral
                                                                                                  experiment_type: steady
                                                                                                  dose_type: Recommended
                                                                                                  co-adm with
                                                                                                    data_source:
                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                    unhealthy, adult
                                                                                                    population:
                                                                                                    age:
                                                                                                    sex:
                                                                                                    food_status:
                                                                                                    n:
                                                                                                    data_source:
                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                    Magnesium decreased all grades,30%
                                                                                                    8 mg 1 times / day steady, oral
                                                                                                    Recommended
                                                                                                    dose: 8 mg 1 times / day
                                                                                                    route: oral
                                                                                                    experiment_type: steady
                                                                                                    dose_type: Recommended
                                                                                                    co-adm with
                                                                                                      data_source:
                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                      unhealthy, adult
                                                                                                      population:
                                                                                                      age:
                                                                                                      sex:
                                                                                                      food_status:
                                                                                                      n:
                                                                                                      data_source:
                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                      Musculoskeletal and connective tissue disorders all grades,31%
                                                                                                      8 mg 1 times / day steady, oral
                                                                                                      Recommended
                                                                                                      dose: 8 mg 1 times / day
                                                                                                      route: oral
                                                                                                      experiment_type: steady
                                                                                                      dose_type: Recommended
                                                                                                      co-adm with
                                                                                                        data_source:
                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                        unhealthy, adult
                                                                                                        population:
                                                                                                        age:
                                                                                                        sex:
                                                                                                        food_status:
                                                                                                        n:
                                                                                                        data_source:
                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                        Dry skin all grades,34%
                                                                                                        8 mg 1 times / day steady, oral
                                                                                                        Recommended
                                                                                                        dose: 8 mg 1 times / day
                                                                                                        route: oral
                                                                                                        experiment_type: steady
                                                                                                        dose_type: Recommended
                                                                                                        co-adm with
                                                                                                          data_source:
                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                          unhealthy, adult
                                                                                                          population:
                                                                                                          age:
                                                                                                          sex:
                                                                                                          food_status:
                                                                                                          n:
                                                                                                          data_source:
                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                          Hemoglobin decreased all grades,35%
                                                                                                          8 mg 1 times / day steady, oral
                                                                                                          Recommended
                                                                                                          dose: 8 mg 1 times / day
                                                                                                          route: oral
                                                                                                          experiment_type: steady
                                                                                                          dose_type: Recommended
                                                                                                          co-adm with
                                                                                                            data_source:
                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                            unhealthy, adult
                                                                                                            population:
                                                                                                            age:
                                                                                                            sex:
                                                                                                            food_status:
                                                                                                            n:
                                                                                                            data_source:
                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                            Albumin decreased all grades,37%
                                                                                                            8 mg 1 times / day steady, oral
                                                                                                            Recommended
                                                                                                            dose: 8 mg 1 times / day
                                                                                                            route: oral
                                                                                                            experiment_type: steady
                                                                                                            dose_type: Recommended
                                                                                                            co-adm with
                                                                                                              data_source:
                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                              unhealthy, adult
                                                                                                              population:
                                                                                                              age:
                                                                                                              sex:
                                                                                                              food_status:
                                                                                                              n:
                                                                                                              data_source:
                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                              Dysgeusia all grades,37%
                                                                                                              8 mg 1 times / day steady, oral
                                                                                                              Recommended
                                                                                                              dose: 8 mg 1 times / day
                                                                                                              route: oral
                                                                                                              experiment_type: steady
                                                                                                              dose_type: Recommended
                                                                                                              co-adm with
                                                                                                                data_source:
                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                unhealthy, adult
                                                                                                                population:
                                                                                                                age:
                                                                                                                sex:
                                                                                                                food_status:
                                                                                                                n:
                                                                                                                data_source:
                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                Decreased appetite all grades,38%
                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                Recommended
                                                                                                                dose: 8 mg 1 times / day
                                                                                                                route: oral
                                                                                                                experiment_type: steady
                                                                                                                dose_type: Recommended
                                                                                                                co-adm with
                                                                                                                  data_source:
                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                  unhealthy, adult
                                                                                                                  population:
                                                                                                                  age:
                                                                                                                  sex:
                                                                                                                  food_status:
                                                                                                                  n:
                                                                                                                  data_source:
                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                  Renal and urinary disorders all grades,38%
                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                  Recommended
                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                  route: oral
                                                                                                                  experiment_type: steady
                                                                                                                  dose_type: Recommended
                                                                                                                  co-adm with
                                                                                                                    data_source:
                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                    unhealthy, adult
                                                                                                                    population:
                                                                                                                    age:
                                                                                                                    sex:
                                                                                                                    food_status:
                                                                                                                    n:
                                                                                                                    data_source:
                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                    Respiratory, thoracic and mediastinal disorders all grades,40%
                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                    Recommended
                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                    route: oral
                                                                                                                    experiment_type: steady
                                                                                                                    dose_type: Recommended
                                                                                                                    co-adm with
                                                                                                                      data_source:
                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                      unhealthy, adult
                                                                                                                      population:
                                                                                                                      age:
                                                                                                                      sex:
                                                                                                                      food_status:
                                                                                                                      n:
                                                                                                                      data_source:
                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                      Sodium decreased all grades,40%
                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                      Recommended
                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                      route: oral
                                                                                                                      experiment_type: steady
                                                                                                                      dose_type: Recommended
                                                                                                                      co-adm with
                                                                                                                        data_source:
                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                        unhealthy, adult
                                                                                                                        population:
                                                                                                                        age:
                                                                                                                        sex:
                                                                                                                        food_status:
                                                                                                                        n:
                                                                                                                        data_source:
                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                        Alanine aminotransferase increased all grades,41%
                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                        Recommended
                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                        route: oral
                                                                                                                        experiment_type: steady
                                                                                                                        dose_type: Recommended
                                                                                                                        co-adm with
                                                                                                                          data_source:
                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                          unhealthy, adult
                                                                                                                          population:
                                                                                                                          age:
                                                                                                                          sex:
                                                                                                                          food_status:
                                                                                                                          n:
                                                                                                                          data_source:
                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                          Alkaline phosphatase increased all grades,41%
                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                          Recommended
                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                          route: oral
                                                                                                                          experiment_type: steady
                                                                                                                          dose_type: Recommended
                                                                                                                          co-adm with
                                                                                                                            data_source:
                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                            unhealthy, adult
                                                                                                                            population:
                                                                                                                            age:
                                                                                                                            sex:
                                                                                                                            food_status:
                                                                                                                            n:
                                                                                                                            data_source:
                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                            Onycholysis all grades,41%
                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                            Recommended
                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                            route: oral
                                                                                                                            experiment_type: steady
                                                                                                                            dose_type: Recommended
                                                                                                                            co-adm with
                                                                                                                              data_source:
                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                              unhealthy, adult
                                                                                                                              population:
                                                                                                                              age:
                                                                                                                              sex:
                                                                                                                              food_status:
                                                                                                                              n:
                                                                                                                              data_source:
                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                              Dry mouth all grades,45%
                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                              Recommended
                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                              route: oral
                                                                                                                              experiment_type: steady
                                                                                                                              dose_type: Recommended
                                                                                                                              co-adm with
                                                                                                                                data_source:
                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                unhealthy, adult
                                                                                                                                population:
                                                                                                                                age:
                                                                                                                                sex:
                                                                                                                                food_status:
                                                                                                                                n:
                                                                                                                                data_source:
                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                Diarrhea all grades,47%
                                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                                Recommended
                                                                                                                                dose: 8 mg 1 times / day
                                                                                                                                route: oral
                                                                                                                                experiment_type: steady
                                                                                                                                dose_type: Recommended
                                                                                                                                co-adm with
                                                                                                                                  data_source:
                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                  unhealthy, adult
                                                                                                                                  population:
                                                                                                                                  age:
                                                                                                                                  sex:
                                                                                                                                  food_status:
                                                                                                                                  n:
                                                                                                                                  data_source:
                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                  Creatinine increased all grades,52%
                                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                                  Recommended
                                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                                  route: oral
                                                                                                                                  experiment_type: steady
                                                                                                                                  dose_type: Recommended
                                                                                                                                  co-adm with
                                                                                                                                    data_source:
                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                    unhealthy, adult
                                                                                                                                    population:
                                                                                                                                    age:
                                                                                                                                    sex:
                                                                                                                                    food_status:
                                                                                                                                    n:
                                                                                                                                    data_source:
                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                    Fatigue all grades,54%
                                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                                    Recommended
                                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                                    route: oral
                                                                                                                                    experiment_type: steady
                                                                                                                                    dose_type: Recommended
                                                                                                                                    co-adm with
                                                                                                                                      data_source:
                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                      unhealthy, adult
                                                                                                                                      population:
                                                                                                                                      age:
                                                                                                                                      sex:
                                                                                                                                      food_status:
                                                                                                                                      n:
                                                                                                                                      data_source:
                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                      Infections and infestations all grades,56%
                                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                                      Recommended
                                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                                      route: oral
                                                                                                                                      experiment_type: steady
                                                                                                                                      dose_type: Recommended
                                                                                                                                      co-adm with
                                                                                                                                        data_source:
                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                        unhealthy, adult
                                                                                                                                        population:
                                                                                                                                        age:
                                                                                                                                        sex:
                                                                                                                                        food_status:
                                                                                                                                        n:
                                                                                                                                        data_source:
                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                        Stomatitis all grades,56%
                                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                                        Recommended
                                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                                        route: oral
                                                                                                                                        experiment_type: steady
                                                                                                                                        dose_type: Recommended
                                                                                                                                        co-adm with
                                                                                                                                          data_source:
                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                          unhealthy, adult
                                                                                                                                          population:
                                                                                                                                          age:
                                                                                                                                          sex:
                                                                                                                                          food_status:
                                                                                                                                          n:
                                                                                                                                          data_source:
                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                          Nervous system disorders all grades,57%
                                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                                          Recommended
                                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                                          route: oral
                                                                                                                                          experiment_type: steady
                                                                                                                                          dose_type: Recommended
                                                                                                                                          co-adm with
                                                                                                                                            data_source:
                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                            unhealthy, adult
                                                                                                                                            population:
                                                                                                                                            age:
                                                                                                                                            sex:
                                                                                                                                            food_status:
                                                                                                                                            n:
                                                                                                                                            data_source:
                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                            Eye disorders all grades,62%
                                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                                            Recommended
                                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                                            route: oral
                                                                                                                                            experiment_type: steady
                                                                                                                                            dose_type: Recommended
                                                                                                                                            co-adm with
                                                                                                                                              data_source:
                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                              unhealthy, adult
                                                                                                                                              population:
                                                                                                                                              age:
                                                                                                                                              sex:
                                                                                                                                              food_status:
                                                                                                                                              n:
                                                                                                                                              data_source:
                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                              Skin and subcutaneous tissue disorders all grades,75%
                                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                                              Recommended
                                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                                              route: oral
                                                                                                                                              experiment_type: steady
                                                                                                                                              dose_type: Recommended
                                                                                                                                              co-adm with
                                                                                                                                                data_source:
                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                unhealthy, adult
                                                                                                                                                population:
                                                                                                                                                age:
                                                                                                                                                sex:
                                                                                                                                                food_status:
                                                                                                                                                n:
                                                                                                                                                data_source:
                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                Phosphate increased all grades,76%
                                                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                                                Recommended
                                                                                                                                                dose: 8 mg 1 times / day
                                                                                                                                                route: oral
                                                                                                                                                experiment_type: steady
                                                                                                                                                dose_type: Recommended
                                                                                                                                                co-adm with
                                                                                                                                                  data_source:
                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                  unhealthy, adult
                                                                                                                                                  population:
                                                                                                                                                  age:
                                                                                                                                                  sex:
                                                                                                                                                  food_status:
                                                                                                                                                  n:
                                                                                                                                                  data_source:
                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                  Metabolism and nutrition disorders all grades,90%
                                                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                                                  Recommended
                                                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                                                  route: oral
                                                                                                                                                  experiment_type: steady
                                                                                                                                                  dose_type: Recommended
                                                                                                                                                  co-adm with
                                                                                                                                                    data_source:
                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                    unhealthy, adult
                                                                                                                                                    population:
                                                                                                                                                    age:
                                                                                                                                                    sex:
                                                                                                                                                    food_status:
                                                                                                                                                    n:
                                                                                                                                                    data_source:
                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                    Gastrointestinal disorders all grades,94%
                                                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                                                    Recommended
                                                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                                                    route: oral
                                                                                                                                                    experiment_type: steady
                                                                                                                                                    dose_type: Recommended
                                                                                                                                                    co-adm with
                                                                                                                                                      data_source:
                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                      unhealthy, adult
                                                                                                                                                      population:
                                                                                                                                                      age:
                                                                                                                                                      sex:
                                                                                                                                                      food_status:
                                                                                                                                                      n:
                                                                                                                                                      data_source:
                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                      Alanine aminotransferase increased grade 3-4,1%
                                                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                                                      Recommended
                                                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                                                      route: oral
                                                                                                                                                      experiment_type: steady
                                                                                                                                                      dose_type: Recommended
                                                                                                                                                      co-adm with
                                                                                                                                                        data_source:
                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                        unhealthy, adult
                                                                                                                                                        population:
                                                                                                                                                        age:
                                                                                                                                                        sex:
                                                                                                                                                        food_status:
                                                                                                                                                        n:
                                                                                                                                                        data_source:
                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                        Alkaline phosphatase increased grade 3-4,1%
                                                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                                                        Recommended
                                                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                                                        route: oral
                                                                                                                                                        experiment_type: steady
                                                                                                                                                        dose_type: Recommended
                                                                                                                                                        co-adm with
                                                                                                                                                          data_source:
                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                          unhealthy, adult
                                                                                                                                                          population:
                                                                                                                                                          age:
                                                                                                                                                          sex:
                                                                                                                                                          food_status:
                                                                                                                                                          n:
                                                                                                                                                          data_source:
                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                          Constipation grade 3-4,1%
                                                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                                                          Recommended
                                                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                                                          route: oral
                                                                                                                                                          experiment_type: steady
                                                                                                                                                          dose_type: Recommended
                                                                                                                                                          co-adm with
                                                                                                                                                            data_source:
                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                            unhealthy, adult
                                                                                                                                                            population:
                                                                                                                                                            age:
                                                                                                                                                            sex:
                                                                                                                                                            food_status:
                                                                                                                                                            n:
                                                                                                                                                            data_source:
                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                            Dysgeusia grade 3-4,1%
                                                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                                                            Recommended
                                                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                                                            route: oral
                                                                                                                                                            experiment_type: steady
                                                                                                                                                            dose_type: Recommended
                                                                                                                                                            co-adm with
                                                                                                                                                              data_source:
                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                              unhealthy, adult
                                                                                                                                                              population:
                                                                                                                                                              age:
                                                                                                                                                              sex:
                                                                                                                                                              food_status:
                                                                                                                                                              n:
                                                                                                                                                              data_source:
                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                              Magnesium decreased grade 3-4,1%
                                                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                                                              Recommended
                                                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                                                              route: oral
                                                                                                                                                              experiment_type: steady
                                                                                                                                                              dose_type: Recommended
                                                                                                                                                              co-adm with
                                                                                                                                                                data_source:
                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                unhealthy, adult
                                                                                                                                                                population:
                                                                                                                                                                age:
                                                                                                                                                                sex:
                                                                                                                                                                food_status:
                                                                                                                                                                n:
                                                                                                                                                                data_source:
                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                Nausea grade 3-4,1%
                                                                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                                                                Recommended
                                                                                                                                                                dose: 8 mg 1 times / day
                                                                                                                                                                route: oral
                                                                                                                                                                experiment_type: steady
                                                                                                                                                                dose_type: Recommended
                                                                                                                                                                co-adm with
                                                                                                                                                                  data_source:
                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                  unhealthy, adult
                                                                                                                                                                  population:
                                                                                                                                                                  age:
                                                                                                                                                                  sex:
                                                                                                                                                                  food_status:
                                                                                                                                                                  n:
                                                                                                                                                                  data_source:
                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                  Oropharyngeal pain grade 3-4,1%
                                                                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                                                                  Recommended
                                                                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                                                                  route: oral
                                                                                                                                                                  experiment_type: steady
                                                                                                                                                                  dose_type: Recommended
                                                                                                                                                                  co-adm with
                                                                                                                                                                    data_source:
                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                    unhealthy, adult
                                                                                                                                                                    population:
                                                                                                                                                                    age:
                                                                                                                                                                    sex:
                                                                                                                                                                    food_status:
                                                                                                                                                                    n:
                                                                                                                                                                    data_source:
                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                    Phosphate increased grade 3-4,1%
                                                                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                                                                    Recommended
                                                                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                                                                    route: oral
                                                                                                                                                                    experiment_type: steady
                                                                                                                                                                    dose_type: Recommended
                                                                                                                                                                    co-adm with
                                                                                                                                                                      data_source:
                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                      unhealthy, adult
                                                                                                                                                                      population:
                                                                                                                                                                      age:
                                                                                                                                                                      sex:
                                                                                                                                                                      food_status:
                                                                                                                                                                      n:
                                                                                                                                                                      data_source:
                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                      Platelets decreased grade 3-4,1%
                                                                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                                                                      Recommended
                                                                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                                                                      route: oral
                                                                                                                                                                      experiment_type: steady
                                                                                                                                                                      dose_type: Recommended
                                                                                                                                                                      co-adm with
                                                                                                                                                                        data_source:
                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                        unhealthy, adult
                                                                                                                                                                        population:
                                                                                                                                                                        age:
                                                                                                                                                                        sex:
                                                                                                                                                                        food_status:
                                                                                                                                                                        n:
                                                                                                                                                                        data_source:
                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                        Pyrexia grade 3-4,1%
                                                                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                                                                        Recommended
                                                                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                                                                        route: oral
                                                                                                                                                                        experiment_type: steady
                                                                                                                                                                        dose_type: Recommended
                                                                                                                                                                        co-adm with
                                                                                                                                                                          data_source:
                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                          unhealthy, adult
                                                                                                                                                                          population:
                                                                                                                                                                          age:
                                                                                                                                                                          sex:
                                                                                                                                                                          food_status:
                                                                                                                                                                          n:
                                                                                                                                                                          data_source:
                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                          Fatigue grade 3-4,10%
                                                                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                                                                          Recommended
                                                                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                                                                          route: oral
                                                                                                                                                                          experiment_type: steady
                                                                                                                                                                          dose_type: Recommended
                                                                                                                                                                          co-adm with
                                                                                                                                                                            data_source:
                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                            unhealthy, adult
                                                                                                                                                                            population:
                                                                                                                                                                            age:
                                                                                                                                                                            sex:
                                                                                                                                                                            food_status:
                                                                                                                                                                            n:
                                                                                                                                                                            data_source:
                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                            Onycholysis grade 3-4,10%
                                                                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                                                                            Recommended
                                                                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                                                                            route: oral
                                                                                                                                                                            experiment_type: steady
                                                                                                                                                                            dose_type: Recommended
                                                                                                                                                                            co-adm with
                                                                                                                                                                              data_source:
                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                              unhealthy, adult
                                                                                                                                                                              population:
                                                                                                                                                                              age:
                                                                                                                                                                              sex:
                                                                                                                                                                              food_status:
                                                                                                                                                                              n:
                                                                                                                                                                              data_source:
                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                              Renal and urinary disorders grade 3-4,10%
                                                                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                                                                              Recommended
                                                                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                                                                              route: oral
                                                                                                                                                                              experiment_type: steady
                                                                                                                                                                              dose_type: Recommended
                                                                                                                                                                              co-adm with
                                                                                                                                                                                data_source:
                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                unhealthy, adult
                                                                                                                                                                                population:
                                                                                                                                                                                age:
                                                                                                                                                                                sex:
                                                                                                                                                                                food_status:
                                                                                                                                                                                n:
                                                                                                                                                                                data_source:
                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                Eye disorders grade 3-4,11%
                                                                                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                                                                                Recommended
                                                                                                                                                                                dose: 8 mg 1 times / day
                                                                                                                                                                                route: oral
                                                                                                                                                                                experiment_type: steady
                                                                                                                                                                                dose_type: Recommended
                                                                                                                                                                                co-adm with
                                                                                                                                                                                  data_source:
                                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                  unhealthy, adult
                                                                                                                                                                                  population:
                                                                                                                                                                                  age:
                                                                                                                                                                                  sex:
                                                                                                                                                                                  food_status:
                                                                                                                                                                                  n:
                                                                                                                                                                                  data_source:
                                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                  Metabolism and nutrition disorders grade 3-4,16%
                                                                                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                                                                                  Recommended
                                                                                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                                                                                  route: oral
                                                                                                                                                                                  experiment_type: steady
                                                                                                                                                                                  dose_type: Recommended
                                                                                                                                                                                  co-adm with
                                                                                                                                                                                    data_source:
                                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                    unhealthy, adult
                                                                                                                                                                                    population:
                                                                                                                                                                                    age:
                                                                                                                                                                                    sex:
                                                                                                                                                                                    food_status:
                                                                                                                                                                                    n:
                                                                                                                                                                                    data_source:
                                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                    Skin and subcutaneous tissue disorders grade 3-4,16%
                                                                                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                                                                                    Recommended
                                                                                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                                                                                    route: oral
                                                                                                                                                                                    experiment_type: steady
                                                                                                                                                                                    dose_type: Recommended
                                                                                                                                                                                    co-adm with
                                                                                                                                                                                      data_source:
                                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                      unhealthy, adult
                                                                                                                                                                                      population:
                                                                                                                                                                                      age:
                                                                                                                                                                                      sex:
                                                                                                                                                                                      food_status:
                                                                                                                                                                                      n:
                                                                                                                                                                                      data_source:
                                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                      Sodium decreased grade 3-4,16%
                                                                                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                                                                                      Recommended
                                                                                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                                                                                      route: oral
                                                                                                                                                                                      experiment_type: steady
                                                                                                                                                                                      dose_type: Recommended
                                                                                                                                                                                      co-adm with
                                                                                                                                                                                        data_source:
                                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                        unhealthy, adult
                                                                                                                                                                                        population:
                                                                                                                                                                                        age:
                                                                                                                                                                                        sex:
                                                                                                                                                                                        food_status:
                                                                                                                                                                                        n:
                                                                                                                                                                                        data_source:
                                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                        Abdominal pain grade 3-4,2%
                                                                                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                                                                                        Recommended
                                                                                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                                                                                        route: oral
                                                                                                                                                                                        experiment_type: steady
                                                                                                                                                                                        dose_type: Recommended
                                                                                                                                                                                        co-adm with
                                                                                                                                                                                          data_source:
                                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                          unhealthy, adult
                                                                                                                                                                                          population:
                                                                                                                                                                                          age:
                                                                                                                                                                                          sex:
                                                                                                                                                                                          food_status:
                                                                                                                                                                                          n:
                                                                                                                                                                                          data_source:
                                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                          Diarrhea grade 3-4,2%
                                                                                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                                                                                          Recommended
                                                                                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                                                                                          route: oral
                                                                                                                                                                                          experiment_type: steady
                                                                                                                                                                                          dose_type: Recommended
                                                                                                                                                                                          co-adm with
                                                                                                                                                                                            data_source:
                                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                            unhealthy, adult
                                                                                                                                                                                            population:
                                                                                                                                                                                            age:
                                                                                                                                                                                            sex:
                                                                                                                                                                                            food_status:
                                                                                                                                                                                            n:
                                                                                                                                                                                            data_source:
                                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                            Dyspnea grade 3-4,2%
                                                                                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                                                                                            Recommended
                                                                                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                                                                                            route: oral
                                                                                                                                                                                            experiment_type: steady
                                                                                                                                                                                            dose_type: Recommended
                                                                                                                                                                                            co-adm with
                                                                                                                                                                                              data_source:
                                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                              unhealthy, adult
                                                                                                                                                                                              population:
                                                                                                                                                                                              age:
                                                                                                                                                                                              sex:
                                                                                                                                                                                              food_status:
                                                                                                                                                                                              n:
                                                                                                                                                                                              data_source:
                                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                              Hematuria grade 3-4,2%
                                                                                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                                                                                              Recommended
                                                                                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                                                                                              route: oral
                                                                                                                                                                                              experiment_type: steady
                                                                                                                                                                                              dose_type: Recommended
                                                                                                                                                                                              co-adm with
                                                                                                                                                                                                data_source:
                                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                unhealthy, adult
                                                                                                                                                                                                population:
                                                                                                                                                                                                age:
                                                                                                                                                                                                sex:
                                                                                                                                                                                                food_status:
                                                                                                                                                                                                n:
                                                                                                                                                                                                data_source:
                                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                Neutrophil count decreased grade 3-4,2%
                                                                                                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                                                                                                Recommended
                                                                                                                                                                                                dose: 8 mg 1 times / day
                                                                                                                                                                                                route: oral
                                                                                                                                                                                                experiment_type: steady
                                                                                                                                                                                                dose_type: Recommended
                                                                                                                                                                                                co-adm with
                                                                                                                                                                                                  data_source:
                                                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                  unhealthy, adult
                                                                                                                                                                                                  population:
                                                                                                                                                                                                  age:
                                                                                                                                                                                                  sex:
                                                                                                                                                                                                  food_status:
                                                                                                                                                                                                  n:
                                                                                                                                                                                                  data_source:
                                                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                  Vomiting grade 3-4,2%
                                                                                                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                                                                                                  Recommended
                                                                                                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                                                                                                  route: oral
                                                                                                                                                                                                  experiment_type: steady
                                                                                                                                                                                                  dose_type: Recommended
                                                                                                                                                                                                  co-adm with
                                                                                                                                                                                                    data_source:
                                                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                    unhealthy, adult
                                                                                                                                                                                                    population:
                                                                                                                                                                                                    age:
                                                                                                                                                                                                    sex:
                                                                                                                                                                                                    food_status:
                                                                                                                                                                                                    n:
                                                                                                                                                                                                    data_source:
                                                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                    Infections and infestations grade 3-4,20%
                                                                                                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                                                                                                    Recommended
                                                                                                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                                                                                                    route: oral
                                                                                                                                                                                                    experiment_type: steady
                                                                                                                                                                                                    dose_type: Recommended
                                                                                                                                                                                                    co-adm with
                                                                                                                                                                                                      data_source:
                                                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                      unhealthy, adult
                                                                                                                                                                                                      population:
                                                                                                                                                                                                      age:
                                                                                                                                                                                                      sex:
                                                                                                                                                                                                      food_status:
                                                                                                                                                                                                      n:
                                                                                                                                                                                                      data_source:
                                                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                      Gastrointestinal disorders grade 3-4,24%
                                                                                                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                                                                                                      Recommended
                                                                                                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                                                                                                      route: oral
                                                                                                                                                                                                      experiment_type: steady
                                                                                                                                                                                                      dose_type: Recommended
                                                                                                                                                                                                      co-adm with
                                                                                                                                                                                                        data_source:
                                                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                        unhealthy, adult
                                                                                                                                                                                                        population:
                                                                                                                                                                                                        age:
                                                                                                                                                                                                        sex:
                                                                                                                                                                                                        food_status:
                                                                                                                                                                                                        n:
                                                                                                                                                                                                        data_source:
                                                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                        Calcium increased grade 3-4,3%
                                                                                                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                                                                                                        Recommended
                                                                                                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                                                                                                        route: oral
                                                                                                                                                                                                        experiment_type: steady
                                                                                                                                                                                                        dose_type: Recommended
                                                                                                                                                                                                        co-adm with
                                                                                                                                                                                                          data_source:
                                                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                          unhealthy, adult
                                                                                                                                                                                                          population:
                                                                                                                                                                                                          age:
                                                                                                                                                                                                          sex:
                                                                                                                                                                                                          food_status:
                                                                                                                                                                                                          n:
                                                                                                                                                                                                          data_source:
                                                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                          Hemoglobin decreased grade 3-4,3%
                                                                                                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                                                                                                          Recommended
                                                                                                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                                                                                                          route: oral
                                                                                                                                                                                                          experiment_type: steady
                                                                                                                                                                                                          dose_type: Recommended
                                                                                                                                                                                                          co-adm with
                                                                                                                                                                                                            data_source:
                                                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                            unhealthy, adult
                                                                                                                                                                                                            population:
                                                                                                                                                                                                            age:
                                                                                                                                                                                                            sex:
                                                                                                                                                                                                            food_status:
                                                                                                                                                                                                            n:
                                                                                                                                                                                                            data_source:
                                                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                            Paronychia grade 3-4,3%
                                                                                                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                                                                                                            Recommended
                                                                                                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                                                                                                            route: oral
                                                                                                                                                                                                            experiment_type: steady
                                                                                                                                                                                                            dose_type: Recommended
                                                                                                                                                                                                            co-adm with
                                                                                                                                                                                                              data_source:
                                                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                              unhealthy, adult
                                                                                                                                                                                                              population:
                                                                                                                                                                                                              age:
                                                                                                                                                                                                              sex:
                                                                                                                                                                                                              food_status:
                                                                                                                                                                                                              n:
                                                                                                                                                                                                              data_source:
                                                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                              Creatinine increased grade 3-4,5%
                                                                                                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                                                                                                              Recommended
                                                                                                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                                                                                                              route: oral
                                                                                                                                                                                                              experiment_type: steady
                                                                                                                                                                                                              dose_type: Recommended
                                                                                                                                                                                                              co-adm with
                                                                                                                                                                                                                data_source:
                                                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                unhealthy, adult
                                                                                                                                                                                                                population:
                                                                                                                                                                                                                age:
                                                                                                                                                                                                                sex:
                                                                                                                                                                                                                food_status:
                                                                                                                                                                                                                n:
                                                                                                                                                                                                                data_source:
                                                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                Nervous system disorders grade 3-4,5%
                                                                                                                                                                                                                8 mg 1 times / day steady, oral
                                                                                                                                                                                                                Recommended
                                                                                                                                                                                                                dose: 8 mg 1 times / day
                                                                                                                                                                                                                route: oral
                                                                                                                                                                                                                experiment_type: steady
                                                                                                                                                                                                                dose_type: Recommended
                                                                                                                                                                                                                co-adm with
                                                                                                                                                                                                                  data_source:
                                                                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                  unhealthy, adult
                                                                                                                                                                                                                  population:
                                                                                                                                                                                                                  age:
                                                                                                                                                                                                                  sex:
                                                                                                                                                                                                                  food_status:
                                                                                                                                                                                                                  n:
                                                                                                                                                                                                                  data_source:
                                                                                                                                                                                                                  https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                  Dry eye grade 3-4,6%
                                                                                                                                                                                                                  8 mg 1 times / day steady, oral
                                                                                                                                                                                                                  Recommended
                                                                                                                                                                                                                  dose: 8 mg 1 times / day
                                                                                                                                                                                                                  route: oral
                                                                                                                                                                                                                  experiment_type: steady
                                                                                                                                                                                                                  dose_type: Recommended
                                                                                                                                                                                                                  co-adm with
                                                                                                                                                                                                                    data_source:
                                                                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                    unhealthy, adult
                                                                                                                                                                                                                    population:
                                                                                                                                                                                                                    age:
                                                                                                                                                                                                                    sex:
                                                                                                                                                                                                                    food_status:
                                                                                                                                                                                                                    n:
                                                                                                                                                                                                                    data_source:
                                                                                                                                                                                                                    https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                    Palmar-plantar erythrodysaesth. grade 3-4,6%
                                                                                                                                                                                                                    8 mg 1 times / day steady, oral
                                                                                                                                                                                                                    Recommended
                                                                                                                                                                                                                    dose: 8 mg 1 times / day
                                                                                                                                                                                                                    route: oral
                                                                                                                                                                                                                    experiment_type: steady
                                                                                                                                                                                                                    dose_type: Recommended
                                                                                                                                                                                                                    co-adm with
                                                                                                                                                                                                                      data_source:
                                                                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                      unhealthy, adult
                                                                                                                                                                                                                      population:
                                                                                                                                                                                                                      age:
                                                                                                                                                                                                                      sex:
                                                                                                                                                                                                                      food_status:
                                                                                                                                                                                                                      n:
                                                                                                                                                                                                                      data_source:
                                                                                                                                                                                                                      https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                      Urinary tract infection grade 3-4,6%
                                                                                                                                                                                                                      8 mg 1 times / day steady, oral
                                                                                                                                                                                                                      Recommended
                                                                                                                                                                                                                      dose: 8 mg 1 times / day
                                                                                                                                                                                                                      route: oral
                                                                                                                                                                                                                      experiment_type: steady
                                                                                                                                                                                                                      dose_type: Recommended
                                                                                                                                                                                                                      co-adm with
                                                                                                                                                                                                                        data_source:
                                                                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                        unhealthy, adult
                                                                                                                                                                                                                        population:
                                                                                                                                                                                                                        age:
                                                                                                                                                                                                                        sex:
                                                                                                                                                                                                                        food_status:
                                                                                                                                                                                                                        n:
                                                                                                                                                                                                                        data_source:
                                                                                                                                                                                                                        https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                        Respiratory, thoracic and mediastinal disorders grade 3-4,7%
                                                                                                                                                                                                                        8 mg 1 times / day steady, oral
                                                                                                                                                                                                                        Recommended
                                                                                                                                                                                                                        dose: 8 mg 1 times / day
                                                                                                                                                                                                                        route: oral
                                                                                                                                                                                                                        experiment_type: steady
                                                                                                                                                                                                                        dose_type: Recommended
                                                                                                                                                                                                                        co-adm with
                                                                                                                                                                                                                          data_source:
                                                                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                          unhealthy, adult
                                                                                                                                                                                                                          population:
                                                                                                                                                                                                                          age:
                                                                                                                                                                                                                          sex:
                                                                                                                                                                                                                          food_status:
                                                                                                                                                                                                                          n:
                                                                                                                                                                                                                          data_source:
                                                                                                                                                                                                                          https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                          Phosphate decreased grade 3-4,9%
                                                                                                                                                                                                                          8 mg 1 times / day steady, oral
                                                                                                                                                                                                                          Recommended
                                                                                                                                                                                                                          dose: 8 mg 1 times / day
                                                                                                                                                                                                                          route: oral
                                                                                                                                                                                                                          experiment_type: steady
                                                                                                                                                                                                                          dose_type: Recommended
                                                                                                                                                                                                                          co-adm with
                                                                                                                                                                                                                            data_source:
                                                                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                            unhealthy, adult
                                                                                                                                                                                                                            population:
                                                                                                                                                                                                                            age:
                                                                                                                                                                                                                            sex:
                                                                                                                                                                                                                            food_status:
                                                                                                                                                                                                                            n:
                                                                                                                                                                                                                            data_source:
                                                                                                                                                                                                                            https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                            Stomatitis grade 3-4,9%
                                                                                                                                                                                                                            8 mg 1 times / day steady, oral
                                                                                                                                                                                                                            Recommended
                                                                                                                                                                                                                            dose: 8 mg 1 times / day
                                                                                                                                                                                                                            route: oral
                                                                                                                                                                                                                            experiment_type: steady
                                                                                                                                                                                                                            dose_type: Recommended
                                                                                                                                                                                                                            co-adm with
                                                                                                                                                                                                                              data_source:
                                                                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                              unhealthy, adult
                                                                                                                                                                                                                              population:
                                                                                                                                                                                                                              age:
                                                                                                                                                                                                                              sex:
                                                                                                                                                                                                                              food_status:
                                                                                                                                                                                                                              n:
                                                                                                                                                                                                                              data_source:
                                                                                                                                                                                                                              https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                              Acute myocardial infarction grade 5,1%
                                                                                                                                                                                                                              Disc. AE
                                                                                                                                                                                                                              8 mg 1 times / day steady, oral
                                                                                                                                                                                                                              Recommended
                                                                                                                                                                                                                              dose: 8 mg 1 times / day
                                                                                                                                                                                                                              route: oral
                                                                                                                                                                                                                              experiment_type: steady
                                                                                                                                                                                                                              dose_type: Recommended
                                                                                                                                                                                                                              co-adm with
                                                                                                                                                                                                                                data_source:
                                                                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                                unhealthy, adult
                                                                                                                                                                                                                                population:
                                                                                                                                                                                                                                age:
                                                                                                                                                                                                                                sex:
                                                                                                                                                                                                                                food_status:
                                                                                                                                                                                                                                n:
                                                                                                                                                                                                                                data_source:
                                                                                                                                                                                                                                https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212018s000lbl.pdf
                                                                                                                                                                                                                                Overview

                                                                                                                                                                                                                                OverviewOther

                                                                                                                                                                                                                                Drug as perpetrator​

                                                                                                                                                                                                                                Drug as perpetrator​

                                                                                                                                                                                                                                TargetModalityActivityMetaboliteClinical evidence
                                                                                                                                                                                                                                likely
                                                                                                                                                                                                                                no
                                                                                                                                                                                                                                no
                                                                                                                                                                                                                                no
                                                                                                                                                                                                                                no
                                                                                                                                                                                                                                no
                                                                                                                                                                                                                                no
                                                                                                                                                                                                                                weak
                                                                                                                                                                                                                                yes
                                                                                                                                                                                                                                yes
                                                                                                                                                                                                                                likely (co-administration study)
                                                                                                                                                                                                                                Comment: Time-dependent inhibitor, Concomitant CYP3A substrates with narrow therapeutic index should be avoided.; Erdafitinib mean ratios (90% CI) for Cmax and AUCinf were 105% (86.7, 127) and 134% (109, 164), respectively, when co-administered with itraconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) relative to erdafitinib alone.
                                                                                                                                                                                                                                Page: 97, (label) 14
                                                                                                                                                                                                                                Drug as victim

                                                                                                                                                                                                                                Drug as victim

                                                                                                                                                                                                                                TargetModalityActivityMetaboliteClinical evidence
                                                                                                                                                                                                                                major
                                                                                                                                                                                                                                yes (co-administration study)
                                                                                                                                                                                                                                Comment: Concomitant fluconazole (moderate CYP2C9/moderate CYP3A inhibitor, 400 mg QD for 11 days) increased erdafitinib (4 mg single dose on Day 5) AUC by 48% and Cmax by 21% (fasted, healthy subjects with CYP2C9*1/*1, *1/*2 genotypes). The contribution of CYP2C9 in the total clearance of erdafitinib isestimated to be 39%.
                                                                                                                                                                                                                                Page: 82, 95, 96
                                                                                                                                                                                                                                major
                                                                                                                                                                                                                                yes (co-administration study)
                                                                                                                                                                                                                                Comment: Concomitant itraconazole (strong CYP3A/P-gp inhibitor, 200 mg QD for 11 days) increased erdafitinib (4 mg single dose on Day 5) AUC by 34% but did not significantly change Cmax (5%)(fasted, healthy subjects with CYP2C9*1/*1, *1/*2 genotypes). The contribution of CYP3A in the total clearance of erdafitinib is estimated to be 20%.
                                                                                                                                                                                                                                Page: 82, 95, 96
                                                                                                                                                                                                                                yes
                                                                                                                                                                                                                                yes (co-administration study)
                                                                                                                                                                                                                                Comment: Concomitant itraconazole (strong CYP3A/P-gp inhibitor, 200 mg QD for 11 days) increased erdafitinib (4 mg single dose on Day 5) AUC by 34% but did not significantly change Cmax (5%)(fasted, healthy subjects with CYP2C9*1/*1, *1/*2 genotypes). The contribution of CYP3A in the total clearance of erdafitinib is estimated to be 20%. Erdafinitib dosse should be separated by >/= 6 h befor or after administration of P-gp substrates with narrow therapeutic index.
                                                                                                                                                                                                                                Page: 95, 96
                                                                                                                                                                                                                                Tox targets

                                                                                                                                                                                                                                Tox targets

                                                                                                                                                                                                                                PubMed

                                                                                                                                                                                                                                PubMed

                                                                                                                                                                                                                                TitleDatePubMed
                                                                                                                                                                                                                                Oncogenic Characterization and Pharmacologic Sensitivity of Activating Fibroblast Growth Factor Receptor (FGFR) Genetic Alterations to the Selective FGFR Inhibitor Erdafitinib.
                                                                                                                                                                                                                                2017 Aug
                                                                                                                                                                                                                                RACK1 forms a complex with FGFR1 and PKM2, and stimulates the growth and migration of squamous lung cancer cells.
                                                                                                                                                                                                                                2017 Nov
                                                                                                                                                                                                                                Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors.
                                                                                                                                                                                                                                2018 Jun
                                                                                                                                                                                                                                Patents

                                                                                                                                                                                                                                Patents

                                                                                                                                                                                                                                Sample Use Guides

                                                                                                                                                                                                                                Cancer patients will receive a 8 milligram (mg) starting dose once daily with option to up-titrate to 9 mg on a 28-day cycle.
                                                                                                                                                                                                                                Route of Administration: Oral
                                                                                                                                                                                                                                Erdafitinib (JNJ-42756493) effectively inhibited pFGFR1, pFGFR3 and pFGFR4
                                                                                                                                                                                                                                Substance Class Chemical
                                                                                                                                                                                                                                Created
                                                                                                                                                                                                                                by admin
                                                                                                                                                                                                                                on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                Edited
                                                                                                                                                                                                                                by admin
                                                                                                                                                                                                                                on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                Record UNII
                                                                                                                                                                                                                                890E37NHMV
                                                                                                                                                                                                                                Record Status Validated (UNII)
                                                                                                                                                                                                                                Record Version
                                                                                                                                                                                                                                • Download
                                                                                                                                                                                                                                Name Type Language
                                                                                                                                                                                                                                ERDAFITINIB
                                                                                                                                                                                                                                INN   USAN   WHO-DD  
                                                                                                                                                                                                                                USAN   INN  
                                                                                                                                                                                                                                Official Name English
                                                                                                                                                                                                                                PAN-FGFR TYROSINE KINASE INHIBITOR JNJ-42756493
                                                                                                                                                                                                                                Common Name English
                                                                                                                                                                                                                                BALVERSA
                                                                                                                                                                                                                                Brand Name English
                                                                                                                                                                                                                                ERDAFITINIB [ORANGE BOOK]
                                                                                                                                                                                                                                Common Name English
                                                                                                                                                                                                                                ERDAFITINIB [INN]
                                                                                                                                                                                                                                Common Name English
                                                                                                                                                                                                                                ERDAFITINIB [USAN]
                                                                                                                                                                                                                                Common Name English
                                                                                                                                                                                                                                JNJ-42756493
                                                                                                                                                                                                                                Code English
                                                                                                                                                                                                                                ERDAFITINIB [WHO-DD]
                                                                                                                                                                                                                                Common Name English
                                                                                                                                                                                                                                1,2-ETHANEDIAMINE, N1-(3,5-DIMETHOXYPHENYL)-N2-(1-METHYLETHYL)-N1-(3-(1-METHYL-1H-PYRAZOL-4-YL)-6-QUINOXALINYL)-
                                                                                                                                                                                                                                Systematic Name English
                                                                                                                                                                                                                                Classification Tree Code System Code
                                                                                                                                                                                                                                NCI_THESAURUS C1967
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                NCI_THESAURUS C129825
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                Code System Code Type Description
                                                                                                                                                                                                                                NCI_THESAURUS
                                                                                                                                                                                                                                C103273
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                DRUG CENTRAL
                                                                                                                                                                                                                                5327
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                CAS
                                                                                                                                                                                                                                1346242-81-6
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                INN
                                                                                                                                                                                                                                10147
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                ChEMBL
                                                                                                                                                                                                                                CHEMBL3545376
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                DRUG BANK
                                                                                                                                                                                                                                DB12147
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                FDA UNII
                                                                                                                                                                                                                                890E37NHMV
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                RXCUI
                                                                                                                                                                                                                                2123125
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                CAS
                                                                                                                                                                                                                                1620332-47-9
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                NO STRUCTURE GIVEN
                                                                                                                                                                                                                                PUBCHEM
                                                                                                                                                                                                                                67462786
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                LACTMED
                                                                                                                                                                                                                                Erdafitinib
                                                                                                                                                                                                                                Created by admin on Sat Jun 26 06:36:01 UTC 2021 , Edited by admin on Sat Jun 26 06:36:01 UTC 2021
                                                                                                                                                                                                                                PRIMARY
                                                                                                                                                                                                                                Related Record Type Details
                                                                                                                                                                                                                                TARGET -> INHIBITOR
                                                                                                                                                                                                                                IC50
                                                                                                                                                                                                                                EXCRETED UNCHANGED
                                                                                                                                                                                                                                URINE
                                                                                                                                                                                                                                TARGET -> INHIBITOR
                                                                                                                                                                                                                                IC50
                                                                                                                                                                                                                                BINDER->LIGAND
                                                                                                                                                                                                                                primarily to alpha-1-acid glycoprotein.
                                                                                                                                                                                                                                BINDING
                                                                                                                                                                                                                                TARGET -> INHIBITOR
                                                                                                                                                                                                                                IC50
                                                                                                                                                                                                                                TRANSPORTER -> SUBSTRATE
                                                                                                                                                                                                                                EXCRETED UNCHANGED
                                                                                                                                                                                                                                FECAL
                                                                                                                                                                                                                                METABOLIC ENZYME -> SUBSTRATE
                                                                                                                                                                                                                                CYP3A4 in the total clearance of erdafitinib is estimated to be 20%.
                                                                                                                                                                                                                                METABOLIC ENZYME -> SUBSTRATE
                                                                                                                                                                                                                                Contribution of CYP2C9 to the total clearance of erdafitinib is estimated to be 39%
                                                                                                                                                                                                                                TARGET -> INHIBITOR
                                                                                                                                                                                                                                IC50
                                                                                                                                                                                                                                Related Record Type Details
                                                                                                                                                                                                                                ACTIVE MOIETY
                                                                                                                                                                                                                                Name Property Type Amount Referenced Substance Defining Parameters References
                                                                                                                                                                                                                                Biological Half-life PHARMACOKINETIC
                                                                                                                                                                                                                                Volume of Distribution PHARMACOKINETIC
                                                                                                                                                                                                                                Tmax PHARMACOKINETIC