Imbruvica

Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Mantle cell lymphoma (MCL) after at least one prior therapy; Waldenström's macroglobulinemia (WM); Marginal zone lymphoma (MZL) requiring systemic therapy after at least one prior anti-CD20-based therapy; Chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy

CLL/SLL: 420 mg orally once daily
MCL: 560 mg orally once daily
WM: 420 mg orally once daily
MZL: 560 mg orally once daily
cGVHD: 420 mg orally once daily
Take consistently at approximately same time each day with water

Capsules: 70 mg, 140 mg; Tablets: 140 mg, 280 mg, 420 mg, 560 mg; Oral suspension: 70 mg/mL

None listed.

• Hemorrhage: Fatal bleeding events reported. Consider benefit-risk with anticoagulants/antiplatelets.
• Infections: Fatal and non-fatal infections including progressive multifocal leukoencephalopathy (PML) and hepatitis B reactivation.
• Cardiac Arrhythmias: Atrial fibrillation/flutter in up to 11% of patients. Higher risk with cardiac risk factors and acute infections.
• Hypertension: Reported in 19% of patients. Monitor and adjust antihypertensive therapy.
• Cytopenias: Grade 3-4 neutropenia (23%), thrombocytopenia (8%), anemia (5%). Monitor monthly.
• Second Primary Malignancies: Including skin cancers (10%) and other carcinomas.
• Tumor Lysis Syndrome: Monitor patients at risk.

Diarrhea (43%), fatigue (28%), musculoskeletal pain (27%), rash (25%), bruising (23%), nausea (21%), hemorrhage (21%), hypertension (19%), upper respiratory tract infection (17%), arthralgia (13%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Ibrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with cysteine 481 in the active site of BTK, inhibiting B-cell receptor signaling, disrupting B-cell adhesion, migration, and homing, and reducing malignant B-cell survival and proliferation.

Median Tmax: 1-2 hours. Half-life: 4-6 hours. Extensively metabolized by CYP3A. Clearance: 1000 L/h. Primarily excreted in feces (80%) and urine (10%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• RESONATE — Ibrutinib vs. ofatumumab in relapsed/refractory CLL. Phase III, n=391.
  🔬 NCT01578707 ↗ 📄 Primary Publication ↗
• RESONATE-2 — Ibrutinib vs. chlorambucil in treatment-naïve CLL (≥65 years). Phase III, n=269.
  🔬 NCT01722487 ↗ 📄 Primary Publication ↗

Imbruvica has FDA-approved indications across the following cancer types covered on PipelineEvidence: