Details
Stereochemistry | ACHIRAL |
Molecular Formula | C27H36N6O3S |
Molecular Weight | 524.678 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=CN=C(NC2=CC=C(OCCN3CCCC3)C=C2)N=C1NC4=CC=CC(=C4)S(=O)(=O)NC(C)(C)C
InChI
InChIKey=JOOXLOJCABQBSG-UHFFFAOYSA-N
InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31)
Molecular Formula | C27H36N6O3S |
Molecular Weight | 524.678 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18394554Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26181658 | http://adisinsight.springer.com/drugs/800027763
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18394554
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26181658 | http://adisinsight.springer.com/drugs/800027763
Fedratinib (SAR-302503, TG-101348) is a selective small-molecule inhibitor of Janus kinase-2. Fedratinib demonstrated therapeutic efficacy in a murine model of myeloproliferative disease. Sanofi was developing Fedratinib for the treatment of myeloproliferative diseases and solid tumors.
The clinical development of fedratinib was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18394554 |
3.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1804 ng/mL |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
2539 ng/mL |
500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1760 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165976 |
680 mg single, oral dose: 680 mg route of administration: Oral experiment type: SINGLE co-administered: |
FEDRATINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
26870 ng × h/mL |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
38712 ng × h/mL |
500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
17800 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165976 |
680 mg single, oral dose: 680 mg route of administration: Oral experiment type: SINGLE co-administered: |
FEDRATINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
41 h |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
62.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24165976 |
680 mg single, oral dose: 680 mg route of administration: Oral experiment type: SINGLE co-administered: |
FEDRATINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8% |
400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
2% |
500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
FEDRATINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
8% |
FEDRATINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Disc. AE: Nausea, Cardiac failure... Other AEs: Diarrhea, Nausea... AEs leading to discontinuation/dose reduction: Nausea (>3) Other AEs:Cardiac failure (grade 3-4, 3%) Cardiac failure (grade 5, 1%) Thrombocytopenia (2%) Myocardial ischemia (2%) Diarrhea (2%) Blood creatinine increased (2%) Diarrhea (>3) Sources: Page: 6.1Nausea (>3) Anemia (6%) Diarrhea (3%) Vomiting (3%) Thrombocytopenia (2%) |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Other AEs: Diarrhea, Nausea... Other AEs: Diarrhea (all grades, 66%) Sources: Page: Table 3Nausea (all grades, 62%) Anemia (all grades, 40%) Vomiting (all grades, 39%) Asthenia (all grades, 19%) Muscle spasms (all grades, 12%) Blood creatinine increased (all grades, 10%) Pain in extremity (all grades, 10%) Alanine aminotransferase increased (all grades, 9%) Headache (all grades, 9%) Weight increased (all grades, 9%) Dizziness (all grades, 8%) Bone pain (all grades, 8%) Urinary tract infection (all grades, 6%) Dysuria (all grades, 6%) Aspartate aminotransferase increased (all grades, 5%) Diarrhea (grade 3-4, 5%) |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Other AEs: Anemia, Vomiting... Other AEs: Anemia (grade 3-4, 30%) Sources: Page: Table 4Vomiting (grade 3-4, 3.1%) Asthenia (grade 3-4, 5%) Blood creatinine increased (grade 3-4, 1%) Thrombocytopenia (all grades, 47%) Neutropenia (all grades, 23%) Lipase increased (all grades, 35%) Hyponatremia (all grades, 26%) Amylase increased (all grades, 24%) Thrombocytopenia (grade 3-4, 12%) Neutropenia (grade 3-4, 5%) Lipase increased (grade 3-4, 10%) Hyponatremia (grade 3-4, 5%) Amylase increased (grade 3-4, 2.1%) Cardiac failure (all grades, 5%) |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Sex: M+F Population Size: 97 Sources: |
Disc. AE: Anemia... AEs leading to discontinuation/dose reduction: Anemia (1%) Sources: |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: Page: 123 |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Sex: M+F Population Size: 97 Sources: Page: 123 |
Disc. AE: Cardiac disorders... AEs leading to discontinuation/dose reduction: Cardiac disorders (grade 5, 2 patients) Sources: Page: 123 |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Disc. AE: Thrombocytopenia, Neutropenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (6%) Sources: Neutropenia (2%) Vomiting (4%) Blood creatinine increased (2%) Diarrhea (2%) Nausea (2%) Amylase increased (1%) Lipase increased (3%) Fatigue (2%) Diarrhea (all grades, 8%) Diarrhea (grade 3-4, 3%) Nausea (all grades, 6%) Nausea (grade 3-4, 4%) Vomiting (all grades, 11%) Vomiting (grade 3-4, 7%) Anemia (all grades, 18%) Anemia (grade 3-4, 14%) Thrombocytopenia (all grades, 7%) Thrombocytopenia (grade 3-4, 6%) Fatigue (all grades, 5%) Fatigue (grade 3-4, 5%) |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Disc. AE: Anemia, Diarrhea... AEs leading to discontinuation/dose reduction: Anemia (2%) Sources: Diarrhea (2%) Nausea (2%) Amylase increased (1%) Lipase increased (1%) Vomiting (all grades, 10%) Vomiting (grade 3-4, 3%) Anemia (all grades, 8%) Anemia (grade 3-4, 5%) Thrombocytopenia (all grades, 3%) Thrombocytopenia (grade 3-4, 2%) Fatigue (all grades, 3%) Fatigue (grade 3-4, 3%) |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: Page: 123 |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: Page: 123 |
Disc. AE: Cardiac disorders... AEs leading to discontinuation/dose reduction: Cardiac disorders (grade 5, 2 patients) Sources: Page: 123 |
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: Page: 20 |
unhealthy, adult n = 1 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: unknown Population Size: 1 Sources: Page: 20 |
|
680 mg 1 times / day multiple, oral MTD Dose: 680 mg, 1 times / day Route: oral Route: multiple Dose: 680 mg, 1 times / day Sources: Page: 68 |
unhealthy, adult n = 31 Health Status: unhealthy Condition: myelofibrosis Age Group: adult Sex: unknown Population Size: 31 Sources: Page: 68 |
|
680 mg single, oral MTD |
healthy, adult n = 2 Health Status: healthy Age Group: adult Sex: M Population Size: 2 Sources: |
Other AEs: Gastrointestinal disorders... |
800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Population Size: 6 Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Thrombocytopenia | 2% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Blood creatinine increased | 2% Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Diarrhea | 2% Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Myocardial ischemia | 2% Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Thrombocytopenia | 2% Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Diarrhea | 3% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Vomiting | 3% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Anemia | 6% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Diarrhea | >3 | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Nausea | >3 | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Nausea | >3 Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Cardiac failure | grade 3-4, 3% Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Cardiac failure | grade 5, 1% Disc. AE |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: 6.1 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: 6.1 |
Blood creatinine increased | all grades, 10% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Pain in extremity | all grades, 10% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Muscle spasms | all grades, 12% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Asthenia | all grades, 19% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Vomiting | all grades, 39% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Anemia | all grades, 40% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Aspartate aminotransferase increased | all grades, 5% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Dysuria | all grades, 6% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Urinary tract infection | all grades, 6% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Nausea | all grades, 62% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Diarrhea | all grades, 66% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Bone pain | all grades, 8% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Dizziness | all grades, 8% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Alanine aminotransferase increased | all grades, 9% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Headache | all grades, 9% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Weight increased | all grades, 9% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Diarrhea | grade 3-4, 5% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 3 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 3 |
Neutropenia | all grades, 23% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Amylase increased | all grades, 24% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Hyponatremia | all grades, 26% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Lipase increased | all grades, 35% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Thrombocytopenia | all grades, 47% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Cardiac failure | all grades, 5% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Blood creatinine increased | grade 3-4, 1% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Lipase increased | grade 3-4, 10% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Thrombocytopenia | grade 3-4, 12% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Amylase increased | grade 3-4, 2.1% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Vomiting | grade 3-4, 3.1% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Anemia | grade 3-4, 30% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Asthenia | grade 3-4, 5% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Hyponatremia | grade 3-4, 5% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Neutropenia | grade 3-4, 5% | 400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: Page: Table 4 |
unhealthy, 27 - 86 years n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 27 - 86 years Sex: M+F Population Size: 96 Sources: Page: Table 4 |
Anemia | 1% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Sex: M+F Population Size: 97 Sources: |
Cardiac disorders | grade 5, 2 patients Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: Page: 123 |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Sex: M+F Population Size: 97 Sources: Page: 123 |
Amylase increased | 1% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Blood creatinine increased | 2% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Diarrhea | 2% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Fatigue | 2% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Nausea | 2% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Neutropenia | 2% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Lipase increased | 3% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Vomiting | 4% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Thrombocytopenia | 6% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Vomiting | all grades, 11% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Anemia | all grades, 18% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Fatigue | all grades, 5% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Nausea | all grades, 6% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Thrombocytopenia | all grades, 7% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Diarrhea | all grades, 8% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Anemia | grade 3-4, 14% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Diarrhea | grade 3-4, 3% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Nausea | grade 3-4, 4% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Fatigue | grade 3-4, 5% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Thrombocytopenia | grade 3-4, 6% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Vomiting | grade 3-4, 7% Disc. AE |
500 mg 1 times / day multiple, oral Studied dose Dose: 500 mg, 1 times / day Route: oral Route: multiple Dose: 500 mg, 1 times / day Sources: |
unhealthy, 65 - 75 years n = 97 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 - 75 years Population Size: 97 Sources: |
Amylase increased | 1% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Lipase increased | 1% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Anemia | 2% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Diarrhea | 2% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Nausea | 2% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Vomiting | all grades, 10% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Fatigue | all grades, 3% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Thrombocytopenia | all grades, 3% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Anemia | all grades, 8% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Thrombocytopenia | grade 3-4, 2% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Fatigue | grade 3-4, 3% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Vomiting | grade 3-4, 3% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Anemia | grade 3-4, 5% Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: intermediate-2 or high-risk myelofibrosis | post-polycythemia vera myelofibrosis | post-essential thrombocythemia myelofibrosis with splenomegaly Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: |
Cardiac disorders | grade 5, 2 patients Disc. AE |
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: Page: 123 |
unhealthy, 65 years (range: 27 - 86 years) n = 96 Health Status: unhealthy Condition: myelofibrosis Age Group: 65 years (range: 27 - 86 years) Sex: M+F Population Size: 96 Sources: Page: 123 |
Gastrointestinal disorders | 680 mg single, oral MTD |
healthy, adult n = 2 Health Status: healthy Age Group: adult Sex: M Population Size: 2 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes [IC50 0.227 uM] | ||||
yes [IC50 0.352 uM] | ||||
yes [IC50 0.78 uM] | ||||
yes [IC50 10.1 uM] | ||||
yes [IC50 100.8 uM] | ||||
yes [IC50 16.4 uM] | ||||
yes [IC50 20.2 uM] | yes (co-administration study) Comment: fedratinib increased exposure of metoprolol by 2x |
|||
yes [IC50 29.9 uM] | ||||
yes [IC50 3 uM] | yes (co-administration study) Comment: fedratinib increased exposure of midazolam by 4x |
|||
yes [IC50 52.2 uM] | ||||
yes [IC50 6.06 uM] | ||||
yes [IC50 9.51 uM] | ||||
yes | yes (co-administration study) Comment: fedratinib increased exposure of omeprazole by 3x |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
major | ||||
major | yes (co-administration study) Comment: ketoconazole increased cmax of fedratinib by 4x |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
|
Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells. | 2013 Sep 1 |
|
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs. | 2015 Jun |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26181658
Fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF: once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18394555
300 nM Fedratinib (SAR-302503, TG-101348) significantly inhibited JAK2V617F+ progenitor-derived colony formation
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 01:55:21 GMT 2023
by
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Sat Dec 16 01:55:21 GMT 2023
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Record UNII |
6L1XP550I6
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Record Status |
Validated (UNII)
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C125450
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6L1XP550I6
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TG101348
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6L1XP550I6
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m12160
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AB-104
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CHEMBL1287853
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SUB126288
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Fedratinib
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100000151872
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Related Record | Type | Details | ||
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|
EXCRETED UNCHANGED |
AMOUNT EXCRETED
FECAL
|
||
|
METABOLIC ENZYME -> SUBSTRATE |
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0‐20%), and FMO3 (0‐33%) in vitro.
|
||
|
TARGET -> INHIBITOR |
INHIBITOR
IC50
|
||
|
BINDER->LIGAND |
BINDING
|
||
|
EXCRETED UNCHANGED |
AMOUNT EXCRETED
URINE
|
||
|
TARGET -> INHIBITOR |
|
||
|
SALT/SOLVATE -> PARENT |
|
||
|
TRANSPORTER -> INHIBITOR |
IC50
|
||
|
TARGET -> INHIBITOR | |||
|
CUMULATIVE EXCRETION |
Only 82% of radioactivity recovered
URINE
|
||
|
TARGET -> INHIBITOR |
INHIBITOR
IC50
|
||
|
TRANSPORTER -> INHIBITOR |
IC50
|
||
|
METABOLIC ENZYME -> SUBSTRATE |
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0‐20%), and FMO3 (0‐33%) in vitro.
|
||
|
TARGET -> INHIBITOR |
IC50
|
||
|
CUMULATIVE EXCRETION |
Only 82% of radioactivity recovered
FECAL
|
||
|
SALT/SOLVATE -> PARENT |
|
||
|
TRANSPORTER -> INHIBITOR |
Patients being treated with fedratinib developed Wernicke?s encephalopathy
(WE) (Sanofi, 2013), a neurological disorder linked to thiamine deficiency (Cook et al., 1998).
IC50
|
||
|
TRANSPORTER -> INHIBITOR |
IC50
|
||
|
TRANSPORTER -> SUBSTRATE |
|
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METABOLIC ENZYME -> SUBSTRATE |
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0‐20%), and FMO3 (0‐33%) in vitro.
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
IC50
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
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METABOLITE LESS ACTIVE -> PARENT |
2 fold less active than parent. accounting for ~ 9% of the radioactivity AUC.
MAJOR
PLASMA
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Blood to Plasma Ratio | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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STEADY-STATE |
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