Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C25H24N6O2 |
Molecular Weight | 440.4971 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=C2C(=NC=N1)N(N=C2C3=CC=C(OC4=CC=CC=C4)C=C3)[C@@H]5CCCN(C5)C(=O)C=C
InChI
InChIKey=XYFPWWZEPKGCCK-GOSISDBHSA-N
InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
Molecular Formula | C25H24N6O2 |
Molecular Weight | 440.4971 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/?term=23425038
Curator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/?term=23425038
Ibrutinib is an orally bioavailable Bruton's tyrosine kinase (BTK) inhibitor indicated for the treatment of mantle cell lymphoma (MCL) patients that previously received at least one therapy. The drug was jointly developed by Janssen Biotech and Pharmacyclics. Ibrutinib selectively binds to Cys-481 residue in the allosteric inhibitory segment of BTK (TK/SH1 domain), and irreversibly blocks its enzymatic activity thus preventing B-cell activation and signaling, totally blocking the B-cell receptor and cytokine receptor pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. Apart from mantle cell lymphoma Ibrutinib is approved for the treatment of chronic lymphocytic leukemia and Waldenstrom Macroglobulinemia.
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=26239089
Curator's Comment: Ibrutinib penetration through the blood-brain barrier was confirmed using plasma and cerebrospinal fluid pharmacokinetic analyses. It has been shown that a low CSF-to-plasma ibrutinib concentration ratio (ranging from 1%-7%) was observed. Ibrutinib CSF distribution may rely on an active influx transport across the blood-brain barrier or a simple diffusion limited by the high plasma protein binding of ibrutinib.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q06187 Gene ID: 695.0 Gene Symbol: BTK Target Organism: Homo sapiens (Human) |
0.5 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | IMBRUVICA Approved UseIndicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy; chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Waldenström's macroglobulinemia (WM). Launch Date2013 |
|||
Primary | IMBRUVICA Approved UseIndicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy; chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Waldenström's macroglobulinemia (WM). Launch Date2013 |
|||
Primary | IMBRUVICA Approved UseIndicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy; chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Waldenstrom Macroglobulinemia (WM). Launch Date2013 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
38.5 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
51.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
147 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
120 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
236 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
485 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
6100 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
864 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
561.6 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01646021 |
560 mg 1 times / day steady, oral dose: 560 mg route of administration: oral experiment type: steady co-administered: |
IBRUTINIB plasma | Homo sapiens population: unhealthy age: sex: food status: |
|
1285 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701 |
560 mg 1 times / day multiple, oral dose: 560 mg route of administration: oral experiment type: multiple co-administered: |
IBRUTINIB unknown | Homo sapiens population: unhealthy age: sex: food status: |
|
1337 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701 |
840 mg 1 times / day multiple, oral dose: 840 mg route of administration: oral experiment type: multiple co-administered: |
IBRUTINIB unknown | Homo sapiens population: unhealthy age: sex: food status: |
|
1485 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701 |
560 mg 1 times / day multiple, oral dose: 560 mg route of administration: oral experiment type: multiple co-administered: |
PCI-45227 unknown | Homo sapiens population: unhealthy age: sex: food status: |
|
1671 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701 |
840 mg 1 times / day multiple, oral dose: 840 mg route of administration: oral experiment type: multiple co-administered: |
PCI-45227 unknown | Homo sapiens population: unhealthy age: sex: food status: |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
11 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
4.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156 |
420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered: |
IBRUTINIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.7% |
IBRUTINIB plasma | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Other AEs: Diarrhea, Nausea... Other AEs: Diarrhea (grade 1-2, 3 patients) Sources: Nausea (grade 1-2, 2 patients) Vomiting (grade 1-2, 2 patients) Constipation (grade 1-2, 1 patient) Decreased appetite (grade 1-2, 1 patient) Dyspepsia (grade 1-2, 1 patient) Fatigue (grade 1-2, 4 patients) Headache (grade 1-2, 2 patients) Muscle spasms (grade 1-2, 3 patients) Myalgia (grade 1-2, 3 patients) Pyrexia (grade 1-2, 2 patients) Rash (grade 1-2, 1 patient) Cough (grade 1-2, 3 patients) Arthralgia (grade 1-2, 2 patients) Edema (grade 1-2, 2 patients) |
8.3 mg/kg 1 times / day steady, oral Dose: 8.3 mg/kg, 1 times / day Route: oral Route: steady Dose: 8.3 mg/kg, 1 times / day Sources: |
unhealthy, 66 years (range: 41-82 years) n = 8 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 66 years (range: 41-82 years) Sex: M+F Population Size: 8 Sources: |
DLT: Hypersensitivity... Dose limiting toxicities: Hypersensitivity (grade 3, 1 patient) Sources: |
2.5 mg/kg 1 times / day steady, oral Dose: 2.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 2.5 mg/kg, 1 times / day Sources: |
unhealthy, 67 years (range: 41-82 years) n = 9 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 67 years (range: 41-82 years) Sex: M+F Population Size: 9 Sources: |
DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 2, 1 patient) Sources: |
420 mg 1 times / day steady, oral Dose: 420 mg, 1 times / day Route: oral Route: steady Dose: 420 mg, 1 times / day Sources: |
unhealthy, 67.0 years (range: 56–71 years) Health Status: unhealthy Condition: chronic lymphocytic leukemia | small lymphocytic lymphoma Age Group: 67.0 years (range: 56–71 years) Sex: M+F Sources: |
DLT: Pneumonia, Sepsis... Disc. AE: Stomatitis... Dose limiting toxicities: Pneumonia (grade 3) AEs leading toSepsis (grade 3) discontinuation/dose reduction: Stomatitis (grade 3, 1 patient) Sources: |
560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Disc. AE: Subdural hematoma, Neutropenia... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Subdural hematoma (1.8%) Other AEs:Neutropenia (grade 3-4, 29%) Thrombocytopenia (grade 3-4, 17%) Anemia (grade 3-4, 9%) Diarrhea (grade 1-2, 46%) Sources: Diarrhea (grade 3-4, 5%) Nausea (grade 1-2, 31%) Constipation (grade 1-2, 25%) Abdominal pain (grade 1-2, 19%) Abdominal pain (grade 3-4, 5%) Vomiting (grade 1-2, 23%) Stomatitis (grade 1-2, 16%) Stomatitis (grade 3-4, 1%) Dyspepsia (grade 1-2, 11%) Upper respiratory tract infection (grade 1-2, 34%) Urinary tract infection (grade 1-2, 11%) Urinary tract infection (grade 3-4, 3%) Pneumonia (grade 1-2, 7%) Pneumonia (grade 3-4, 7%) Skin infection (grade 1-2, 9%) Skin infection (grade 3-4, 5%) Sinusitis (grade 1-2, 12%) Sinusitis (grade 3-4, 1%) Fatigue (grade 1-2, 36%) Fatigue (grade 3-4, 5%) Peripheral edema (grade 1-2, 32%) Peripheral edema (grade 3-4, 3%) Pyrexia (grade 1-2, 17%) Pyrexia (grade 3-4, 1%) Asthenia (grade 1-2, 11%) Asthenia (grade 3-4, 3%) Bruising (grade 1-2, 30%) Rash (grade 1-2, 22%) Rash (grade 3-4, 3%) Petechiae (grade 1-2, 11%) Musculoskeletal pain (grade 1-2, 36%) Musculoskeletal pain (grade 3-4, 1%) Muscle spasms (grade 1-2, 14%) Arthralgia (grade 1-2, 11%) Dyspnea (grade 1-2, 23%) Dyspnea (grade 3-4, 4%) Cough (grade 1-2, 19%) Epistaxis (grade 1-2, 11%) Decreased appetite (grade 1-2, 19%) Decreased appetite (grade 3-4, 2%) Dehydration (grade 1-2, 8%) Dehydration (grade 3-4, 4%) Dizziness (grade 1-2, 14%) Headache (grade 1-2, 13%) Platelets decreased (grade 1-2, 40%) Platelets decreased (grade 3-4, 17%) Neutrophil count decreased (grade 1-2, 18%) Neutrophil count decreased (grade 3-4, 29%) Hemoglobin decreased (grade 1-2, 32%) Hemoglobin decreased (grade 3-4, 9%) Hyperuricemia (15%) Hemorrhage (grade 3, 5%) Infection (grade 3, 25%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Constipation | grade 1-2, 1 patient | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Decreased appetite | grade 1-2, 1 patient | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Dyspepsia | grade 1-2, 1 patient | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Rash | grade 1-2, 1 patient | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Arthralgia | grade 1-2, 2 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Edema | grade 1-2, 2 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Headache | grade 1-2, 2 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Nausea | grade 1-2, 2 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Pyrexia | grade 1-2, 2 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Vomiting | grade 1-2, 2 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Cough | grade 1-2, 3 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Diarrhea | grade 1-2, 3 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Muscle spasms | grade 1-2, 3 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Myalgia | grade 1-2, 3 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Fatigue | grade 1-2, 4 patients | 12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: |
unhealthy, 65 years (range: 41-82 years) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 Sources: |
Hypersensitivity | grade 3, 1 patient DLT |
8.3 mg/kg 1 times / day steady, oral Dose: 8.3 mg/kg, 1 times / day Route: oral Route: steady Dose: 8.3 mg/kg, 1 times / day Sources: |
unhealthy, 66 years (range: 41-82 years) n = 8 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 66 years (range: 41-82 years) Sex: M+F Population Size: 8 Sources: |
Neutropenia | grade 2, 1 patient DLT, Disc. AE |
2.5 mg/kg 1 times / day steady, oral Dose: 2.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 2.5 mg/kg, 1 times / day Sources: |
unhealthy, 67 years (range: 41-82 years) n = 9 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 67 years (range: 41-82 years) Sex: M+F Population Size: 9 Sources: |
Stomatitis | grade 3, 1 patient Disc. AE |
420 mg 1 times / day steady, oral Dose: 420 mg, 1 times / day Route: oral Route: steady Dose: 420 mg, 1 times / day Sources: |
unhealthy, 67.0 years (range: 56–71 years) Health Status: unhealthy Condition: chronic lymphocytic leukemia | small lymphocytic lymphoma Age Group: 67.0 years (range: 56–71 years) Sex: M+F Sources: |
Pneumonia | grade 3 DLT, Disc. AE |
420 mg 1 times / day steady, oral Dose: 420 mg, 1 times / day Route: oral Route: steady Dose: 420 mg, 1 times / day Sources: |
unhealthy, 67.0 years (range: 56–71 years) Health Status: unhealthy Condition: chronic lymphocytic leukemia | small lymphocytic lymphoma Age Group: 67.0 years (range: 56–71 years) Sex: M+F Sources: |
Sepsis | grade 3 DLT, Disc. AE |
420 mg 1 times / day steady, oral Dose: 420 mg, 1 times / day Route: oral Route: steady Dose: 420 mg, 1 times / day Sources: |
unhealthy, 67.0 years (range: 56–71 years) Health Status: unhealthy Condition: chronic lymphocytic leukemia | small lymphocytic lymphoma Age Group: 67.0 years (range: 56–71 years) Sex: M+F Sources: |
Subdural hematoma | 1.8% Disc. AE |
560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Hyperuricemia | 15% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Arthralgia | grade 1-2, 11% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Asthenia | grade 1-2, 11% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Dyspepsia | grade 1-2, 11% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Epistaxis | grade 1-2, 11% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Petechiae | grade 1-2, 11% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Urinary tract infection | grade 1-2, 11% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Sinusitis | grade 1-2, 12% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Headache | grade 1-2, 13% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Dizziness | grade 1-2, 14% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Muscle spasms | grade 1-2, 14% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Stomatitis | grade 1-2, 16% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Pyrexia | grade 1-2, 17% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Neutrophil count decreased | grade 1-2, 18% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Abdominal pain | grade 1-2, 19% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Cough | grade 1-2, 19% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Decreased appetite | grade 1-2, 19% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Rash | grade 1-2, 22% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Dyspnea | grade 1-2, 23% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Vomiting | grade 1-2, 23% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Constipation | grade 1-2, 25% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Bruising | grade 1-2, 30% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Nausea | grade 1-2, 31% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Hemoglobin decreased | grade 1-2, 32% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Peripheral edema | grade 1-2, 32% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Upper respiratory tract infection | grade 1-2, 34% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Fatigue | grade 1-2, 36% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Musculoskeletal pain | grade 1-2, 36% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Platelets decreased | grade 1-2, 40% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Diarrhea | grade 1-2, 46% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Pneumonia | grade 1-2, 7% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Dehydration | grade 1-2, 8% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Skin infection | grade 1-2, 9% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Infection | grade 3, 25% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Hemorrhage | grade 3, 5% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Musculoskeletal pain | grade 3-4, 1% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Pyrexia | grade 3-4, 1% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Sinusitis | grade 3-4, 1% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Stomatitis | grade 3-4, 1% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Platelets decreased | grade 3-4, 17% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Thrombocytopenia | grade 3-4, 17% Disc. AE |
560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Decreased appetite | grade 3-4, 2% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Neutrophil count decreased | grade 3-4, 29% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Neutropenia | grade 3-4, 29% Disc. AE |
560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Asthenia | grade 3-4, 3% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Peripheral edema | grade 3-4, 3% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Rash | grade 3-4, 3% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Urinary tract infection | grade 3-4, 3% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Dehydration | grade 3-4, 4% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Dyspnea | grade 3-4, 4% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Abdominal pain | grade 3-4, 5% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Diarrhea | grade 3-4, 5% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Fatigue | grade 3-4, 5% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Skin infection | grade 3-4, 5% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Pneumonia | grade 3-4, 7% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Hemoglobin decreased | grade 3-4, 9% | 560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Anemia | grade 3-4, 9% Disc. AE |
560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: |
unhealthy, 68 years (range: 40 - 84 years) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: In a dedicated drug-interaction trial, concomitant ketoconazole (strong CYP3A4 inhibitor) increased ibrutinib Cmax 29-fold and AUC 24-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=9 Page: - |
|||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: 36.0 |
no [Ki >100 uM] | |||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=43 Page: 43.0 |
no | |||
yes | ||||
yes | yes (pharmacogenomic study) Comment: n the mass balance trial (n = 6), the mean ibrutinib and the active metabolite PCI-45227 AUCs were 10% and 29% higher, respectively in CYP2D6 poor metabolizers (PMs, N=2) compared with the mean AUCs in CYP2D6 extensive metabolizers (EMs, N=4). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=34 Page: - |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=19 Page: 19.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Bruton's tyrosine kinase inhibitors: approaches to potent and selective inhibition, preclinical and clinical evaluation for inflammatory diseases and B cell malignancies. | 2012 May 24 |
|
Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. | 2013 Jul 4 |
|
Ibrutinib in pretreated Waldenström's macroglobulinaemia. | 2015 May |
|
Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. | 2015 May |
|
Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. | 2015 Sep 24 |
Patents
Sample Use Guides
MCL: 560 mg taken orally once daily (four 140 mg capsules once daily); CLL/SLL and WM: 420 mg taken orally once daily (three 140 mg capsules once daily). Capsules should be taken orally with a glass of water.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=24270740
CLL-B cells were freshly isolated from the peripheral blood of the CLL patients before the initiation of ibrutinib therapy, cultured in vitro for 72 h in the presence or absence of ibrutinib, and analyzed with annexin V and 7AAD double staining. CLL cells were cultured alone in the presence or absence of various concentrations of ibrutinib from 0.01 to 10 uM.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 20:18:17 GMT 2023
by
admin
on
Fri Dec 15 20:18:17 GMT 2023
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Record UNII |
1X70OSD4VX
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
462314
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
574317
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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EMA ASSESSMENT REPORTS |
IMBRUVIA (AUTHORIZED: LYMPHOMA, MANTLE-CELL)
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
622317
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
409713
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
462214
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
444414
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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EMA ASSESSMENT REPORTS |
IMBRUVICA (AUTHORIZED: LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL)
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
407413
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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NCI_THESAURUS |
C124801
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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EU-Orphan Drug |
EU/3/13/1203
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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WHO-ATC |
L01XE27
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
395513
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
525616
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
383112
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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NDF-RT |
N0000175605
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
462114
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
366212
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
368012
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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FDA ORPHAN DRUG |
397313
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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NCI_THESAURUS |
C129825
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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Code System | Code | Type | Description | ||
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Ibrutinib
Created by
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PRIMARY | |||
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DTXSID60893450
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PRIMARY | |||
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9566
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PRIMARY | |||
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100000144394
Created by
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PRIMARY | |||
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EU/3/12/984(POSITIVE)
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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PRIMARY | On 26 April 2012, orphan designation (EU/3/12/984) was granted by the European Commission to Nexus Oncology Ltd, United Kingdom, for 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one for the treatment of chronic lymphocytic leukaemia. The sponsorship was transferred to Janssen-Cilag International N.V, Belgium, in January 2013. | ||
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76612
Created by
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PRIMARY | |||
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YY-102
Created by
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PRIMARY | |||
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DB09053
Created by
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PRIMARY | |||
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1X70OSD4VX
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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1X70OSD4VX
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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m11677
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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Ibrutinib
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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6912
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admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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CHEMBL1873475
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admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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C81934
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admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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4810
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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1442981
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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24821094
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SUB120863
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admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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936563-96-1
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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8260
Created by
admin on Fri Dec 15 20:18:17 GMT 2023 , Edited by admin on Fri Dec 15 20:18:17 GMT 2023
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Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR RESISTANT |
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PROTEIN ADDUCT FORMATION |
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TARGET -> INHIBITOR |
Binds to a cysteine residue (Cys-481) in the BTK active site
IRREVERSIBLE INHIBITOR
IC50
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OFF-TARGET->INHIBITOR |
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EXCRETED UNCHANGED |
FECAL
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OFF-TARGET->INHIBITOR |
IC50
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OFF-TARGET->INHIBITOR |
IC50
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OFF-TARGET->INHIBITOR |
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ENANTIOMER -> ENANTIOMER |
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METABOLIC ENZYME -> SUBSTRATE |
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
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METABOLITE ACTIVE -> PARENT |
Concentration higher than IBRUTINIB
MAJOR
PLASMA
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE ACTIVE -> PARENT |
FECAL
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
FECAL
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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