Ibrutinib

DEA Class; Rx

Common Brand Names; Imbruvica

• Antineoplastics, Tyrosine Kinase Inhibitor

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Also indicated for CLL/SLL in patients with 17p deletion

Indicated in patients who have received at least 1 previous therapy

Indicated as monotherapy or in combination with rituximab

Indicated in patients who require systemic therapy and have received at least one prior anti-CD20-based therapy

Indicated for chronic graft versus host disease (cGVHD) in adults who failed >1 lines of systemic therapy

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• Percentages are for all grades of toxicity unless otherwise noted
• Increased serum creatinine, 1.5 x ULN (67%)
• Platelets decreased (57%)
• Diarrhea (51%)
• Hemorrhage (48%)
• Neutrophils decreased (47%)
• Hemoglobin decreased (41%)
• Fatigue (41%)
• Musculoskeletal pain (37%)
• Peripheral edema (35%)
• URI infection (34%)
• Nausea (31%)
• Bruising (30%)
• Neutropenia, Grade 3 or 4 (29%)
• Dyspnea (27%)
• Constipation (25%)
• Rash (25%)
• Abdominal pain (24%)
• Vomiting (23%)
• Decreased appetite (21%)
• Cough (19%)
• Pyrexia (18%)
• Stomatitis (17%)
• Thrombocytopenia, Grade 3 or 4 (17%)
• UTI infection (14%)
• Pneumonia (14%)
• Skin infections (14%)
• Asthenia (14%)
• Muscle spasms (14%)
• Dizziness (14%)
• Sinusitis (13%)
• Headache (13%)
• Dehydration (12%)
• Dyspepsia (11%)
• Petechiae (11%)
• Arthralgia (11%)
• Epistaxis (11%)

Fatal and nonfatal infection (eg, bacterial, viral, or fungal) reported; 24% of patients had Grade ≥3; consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections; monitor and evaluate for fever and infections; treat appropriately

Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (13-29%), thrombocytopenia (5-17%), and anemia (0-13%) occurred in patients with B-cell malignancies treated with ibrutinib monotherapy; monitor CBC monthly

Fatal and serious cases of renal failure occurred; treatment-emergent increases in creatinine levels up to 1.5 x ULN occurred in 67% (MCL) and 23% (CLL) and from 1.5-3x ULN in 9% (MCL) and 4% (CLL); periodically monitor creatinine and maintain hydration

Other malignancies (5-14%) reported including carcinomas (1-3%); the most frequent second primary malignancy was nonmelanoma skin cancer (4-11%)

Hypertension (12% of any grade) reported with a median time to onset of 5.9 months; monitor for new onset hypertension or hypertension that is not adequately controlled after initiating ibrutinib; monitor blood pressure in patients receiving therapy; initiate or adjust anti-hypertensive medication throughout treatment as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension

Tumor lysis syndrome infrequently reported; assess the baseline risk (eg, high tumor burden) and take appropriate precautions; treat as appropriate

Based on findings in animals, can cause fetal harm when administered to a pregnant woman (see Pregnancy)

Metabolized in the liver; although no clinical trials have been completed in patients with impaired hepatic function, ibrutinib systemic exposure was ~6-fold higher in patients (N=3) with moderate hepatic impairment (Child-Pugh B) compared to healthy volunteers

Safety has not been evaluated in patients with mild to severe hepatic impairment by Child-Pugh criteria; reduce recommended dose when administering to patients with mild or moderate hepatic impairment (Child-Pugh class A and B); monitor patients more frequently for adverse reactions

Verify pregnancy status of females of reproductive potential prior to initiating ibrutinib

Can cause fetal harm when administered to pregnant women; advise females of reproductive potential to avoid pregnancy while taking ibrutinib and for up to 1 month after ending treatment; if this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, inform of the potential hazard to a fetus

Advise men to avoid fathering a child while receiving ibrutinib, and for 1 month following the last dose of ibrutinib

No information regarding the presence of ibrutinib or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production; because of potential for serious adverse reactions in breastfed child, advise women not to breastfeed during treatment and for 1 week after last dose

Ibrutinib 

capsule

• 70mg
• 140mg

tablet

• 140mg
• 280mg
• 420mg
• 560mg