Iclusig

Chronic myeloid leukemia (CML) — chronic, accelerated, or blast phase resistant to or intolerant of at least two prior kinase inhibitors; Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) — resistant to or intolerant of at least two prior kinase inhibitors; CML or Ph+ ALL with T315I mutation

Starting dose: 45 mg orally once daily
With or without food
Dose reduction for response (CP-CML with BCR-ABL1 ≤1%): Reduce to 15 mg once daily
Dose reductions for toxicity: 30 mg → 15 mg → (consider discontinuation)

Tablets: 10 mg, 15 mg, 30 mg, 45 mg

None listed.

• Arterial Occlusive Events: MI, stroke, peripheral arterial disease in 26% of patients. Monitor cardiovascular risk factors. Consider dose reduction.
• Venous Thromboembolic Events: DVT, PE in 6%.
• Heart Failure: 9% including fatal cases. Monitor cardiac function.
• Hepatotoxicity: Fatal hepatic failure reported. Monitor LFTs at baseline and monthly.
• Hypertension: 68% (Grade 3: 12%). Control BP before and during treatment.
• Pancreatitis: 7% (Grade 3-4: 5%). Monitor lipase monthly for first 2 months then periodically.
• Hemorrhage: Including fatal cerebral hemorrhage (1%).
• Fluid Retention: 31% including pleural effusion (7%).
• Cardiac Arrhythmias: 19%. Monitor for signs/symptoms.
• Myelosuppression: Thrombocytopenia (40%), neutropenia (23%), anemia (20%). Monitor CBC every 2 weeks for 3 months then monthly.
• Ocular Toxicities: Including blurred vision, dry eyes, retinal toxicity.

Hypertension (68%), rash (44%), abdominal pain (42%), fatigue (39%), headache (37%), dry skin (32%), constipation (37%), arthralgia (31%), nausea (29%), pyrexia (25%), thrombocytopenia (40%), myalgia (22%), pain in extremity (20%)

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.

Ponatinib is a kinase inhibitor designed to be active against native and mutant BCR-ABL, including the T315I gatekeeper mutation that confers resistance to all other approved BCR-ABL inhibitors. Ponatinib also inhibits VEGFR, PDGFR, FGFR, EPH receptors, and SRC family kinases, and KIT, RET, TIE2, and FLT3.

Tmax: ≤6 hours. Half-life: approximately 24 hours. Protein binding: >99%. Metabolized by CYP3A4 and to a lesser extent CYP2C8 and CYP2D6. Fecal excretion (87%), urinary excretion (5%).

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

• PACE — Ponatinib in resistant/intolerant CML and Ph+ ALL. Phase II, n=449.
  🔬 NCT01207440 ↗ 📄 Primary Publication ↗

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