IMBRUVICA is a kinase inhibitor indicated for the treatment of patients with:

• Mantle cell lymphoma (MCL) who have received at least one prior therapy (1.1).
  Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
• Chronic lymphocytic leukemia (CLL) (1.2).
• Chronic lymphocytic leukemia with 17p deletion (1.3).
• Waldenström's macroglobulinemia (WM) (1.4).

• MCL: 560 mg taken orally once daily (four 140 mg capsules once daily) (2.2).
• CLL and WM: 420 mg taken orally once daily (three 140 mg capsules once daily) (2.2).

Capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules (2.1).

Capsule: 140 mg (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS

• Hemorrhage: Monitor for bleeding and manage (5.1).
• Infections: Monitor patients for fever and infections, eva luate promptly, and treat (5.2).
• Cytopenias: Check complete blood counts monthly (5.3).
• Atrial Fibrillation: Monitor for atrial fibrillation and manage (5.4).
• Hypertension: Monitor blood pressure and treat (5.5).
• Second Primary Malignancies: Other malignancies have occurred in patients, including skin cancers, and other carcinomas (5.6).
• Tumor Lysis Syndrome (TLS): Assess baseline risk and take precautions. Monitor and treat for TLS (5.7).
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise women of the potential risk to a fetus and to avoid pregnancy while taking the drug and for 1 month after cessation of therapy. Advise men to avoid fathering a child during the same time period (5.8, 8.3).

The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia, diarrhea, anemia, neutropenia, musculoskeletal pain, fatigue, bruising, nausea, rash, and upper respiratory tract infection (6).

To report SUSPECTED ADVERSE REACTIONS, contact Pharmacyclics at 1-877-877-3536 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• CYP3A Inhibitors: Avoid co-administration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce IMBRUVICA dose (2.4, 7.1).
• CYP3A Inducers: Avoid co-administration with strong CYP3A inducers (7.2).

Hepatic Impairment: Avoid use of IMBRUVICA in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose (2.5, 8.7).