Generic Name and Formulations:
Ponatinib 15mg, 30mg, 45mg; tabs; contains lactose.
Takeda Pharmaceuticals USA, Inc.
Indications for ICLUSIG:
Treatment of adults with chronic, accelerated, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated. Treatment of adults with T315I-positive CML (chronic, accelerated, or blast phase) or T315I-positive Ph+ ALL.
Limitations Of use:
Not for treating patients with newly diagnosed chronic phase CML.
Swallow whole. ≥18yrs: initially 45mg once daily; consider reducing dose in chronic and accelerated phase CML if major cytogenic response achieved. Consider discontinuing if no response occurred by 3 months. Concomitant strong CYP3A inhibitors or hepatic impairment: reduce to 30mg once daily. Dose modification for hematologic and non-hematologic toxicity: see full labeling.
<18yrs: not established.
Risk of venous thromboembolism and arterial occlusion (including fatal MI, stroke, stenosis of arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures) in patients with or without CV risk factors (including ≤50yrs old, or increasing age, history of ischemia, HTN, diabetes, hyperlipidemia); monitor and interrupt or discontinue if occurs. Monitor for signs/symptoms of heart failure; interrupt or consider discontinuing if develops or worsens. Monitor hepatic function at baseline, then at least monthly or as needed; interrupt, reduce or discontinue as clinically indicated. Monitor and manage BP elevations; interrupt, reduce dose or discontinue if not controlled; evaluate for renal artery stenosis if significant worsening, labile or treatment-resistant hypertension occurs. Risk of pancreatitis; check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated; do not restart until complete resolution and lipase levels <1.5XULN. Increased toxicity in newly diagnosed chronic phase CML: not recommended. Monitor for neuropathy; consider interrupting and evaluate if suspected. Conduct eye exams at baseline and periodically during treatment. Interrupt therapy and evaluate for serious/severe hemorrhage or cardiac arrhythmias. Monitor for fluid retention; interrupt, reduce, or discontinue as indicated. Obtain CBCs every 2 weeks for the first 3 months, then monthly or as indicated. Tumor lysis syndrome; ensure adequate hydration and treat uric levels prior to therapy. Compromised wound healing (withhold for 1 week prior to major surgery) and GI perforation. Interrupt therapy if reversible posterior leukoencephalopathy syndrome occurs; resume only when resolved and if the benefit outweighs the risk. Elderly. Embryo-fetal toxicity. Pregnancy (avoid). Females of reproductive potential should use effective contraception during and for 3 weeks after last dose. Nursing mothers: not recommended.
Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole); see Adult dose. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort). Caution with concomitant drugs that elevate gastric pH (eg, PPIs), P-gp and ABCG2 substrates.
Hypertension, rash, abdominal pain, fatigue, headache, dry skin, arterial occlusion, constipation, arthralgia, nausea, pyrexia, diarrhea, increased lipase, vomiting, myalgia, extremity pain; myelosuppression.
Hepatic (CYP3A4, 2C8, 2D6, 3A5); 99% protein bound.
Tabs 15mg—30, 60; 30mg, 45mg—30