Ibrutinib

IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion. Adult patients with Waldenström’s macroglobulinemia (WM). Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.

Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK). Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Nonclinical studies show that ibrutinib inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro.

CLL/SLL and WM: 420 mg taken orally once daily. cGVHD: • Patients 12 years and older: 420 mg taken orally once daily. • Patients 1 to less than 12 years of age: 240 mg/m 2 taken orally once daily (up to a dose of 420 mg). Tablets or capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets. See full prescribing information for oral suspension administration instructions.

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Hemorrhage: Monitor for bleeding and manage. Infections: Monitor patients for fever and infections, evaluate promptly, and treat. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death: Monitor for symptoms of arrhythmias and cardiac failure and manage. Hypertension: Monitor blood pressure and treat. Cytopenias: Check complete blood counts monthly. Second Primary Malignancies: Other malignancies have occurred in patients, including skin cancers, and other carcinomas. Hepatotoxicity, Including Drug- Induced Liver Injury: Monitor hepatic function throughout treatment. Tumor Lysis Syndrome (TLS): Assess baseline risk and take precautions. Monitor and treat for TLS. Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hemorrhage Infections Cardiac Arrhythmias, Cardiac Failure, and Sudden Death Hypertension Cytopenias Second Primary Malignancies Hepatotoxicity, including DILI Tumor Lysis Syndrome The most common (≥30%) adverse reactions in patients with B-cell malignancies are thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, and nausea. The most common (≥20%) adverse reactions in adult or pediatric patients with cGVHD are fatigue, anemia, bruising, diarrhea, thrombocytopenia, musculoskeletal pain, pyrexia, muscle spasms, stomatitis, hemorrhage, nausea, abdominal pain, pneumonia, and headache.

CYP3A Inhibitors: Modify IMBRUVICA dose as described. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. Effect of CYP3A Inhibitors on Ibrutinib The coadministration of IMBRUVICA with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA if these inhibitors will be used short-term (such as anti-infectives for seven days or less). Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A.

Store bottles at room temperature 20°C to 25°C (68°F to 77°F). Brief exposure to 15°C to 30°C (59°F to 86°F) permitted. Carton of one folded blister card containing two 14-count blister strips for a total of 28 tablets: NDC 57962-420-28 Store tablets in original packaging at room temperature 20°C to 25°C (68°F to 77°F). Store the oral suspension bottle at 2°C to 25°C (36°F to 77°F). Do not freeze.