e, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, grapefruit products and ciprofloxacin) [see Drug Interactions (7.1)].
Patients taking concomitant strong or moderate CYP3A inhibitors should be monitored more closely for signs of IMBRUVICA toxicity.
2.5 Missed Dose
If a dose of IMBRUVICA is not taken at the scheduled time, it can be taken as soon as possible on the same day with a return to the normal schedule the following day. Extra capsules of IMBRUVICA should not be taken to make up for the missed dose.
3 DOSAGE FORMS AND STRENGTHS
140 mg capsules
4 CONTRAINDICATIONS
None
5 WARNINGS AND PRECAUTIONS
5.1 Hemorrhage
Five percent of patients with MCL had Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Overall, bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily.
The mechanism for the bleeding events is not well understood.
Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapies.
Consider the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding [see Clinical Studies (14.1)].
5.2 Infections
Fatal and non-fatal infections have occurred with IMBRUVICA therapy. At least 25% of patients with MCL had infections Grade 3 or greater NCI Common Terminology Criteria for Adverse Events (CTCAE) [See Adverse Reactions (6)]. Monitor patients for fever and infections and eva luate promptly.
5.3 Myelosuppression
Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%). Monitor complete blood counts monthly.
5.4 Renal Toxicity
Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Treatment-emergent increases in creatinine levels up to 1.5 times the upper limit of normal occurred in 67% of patients and from 1.5 to 3 times the upper limit of normal in 9% of patients. Periodically monitor creatinine levels. Maintain hydration.
5.5 Second Primary Malignancies
Other malignancies (5%) have occurred in patients with MCL who have been treated with IMBRUVICA, including skin cancers (4%), and other carcinomas (1%).
5.6 Embryo-Fetal Toxicity
Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Ibrutinib caused malformations in rats at exposures 14 times those reported in patients with MCL receiving the ibrutinib dose of 560 mg per day. Reduced fetal weights were observed at lower exposures. Advise women to avoid becoming pregnant while taking IMBRUVICA. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of the labeling:
Hemorrhage [see Warnings and Precautions (5.1)]
Infections [see Warnings and Precautions (5.2)]
Myelosuppression [see Warnings and Precautions (5.3)]
Renal Toxicity [see Warnings and Precautions (5.4)]
Second Primary Malignancies [see Warnings and Precautions (5.5)]
Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a |
