Leukemias, lymphomas, and other hematologic cancers:

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.

Adult:

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.

Children:

<18yrs: not established.

Boxed Warning:

Arterial occlusion. Venous thromboembolism. Heart failure. Hepatotoxicity.

Warnings/Precautions:

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 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 <1.5×ULN. 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. May impair wound healing; withhold for ≥1 week prior to elective surgery; do not give for ≥2 weeks after major surgery and until adequate wound healing. Permanently discontinue if GI perforation occurs. Interrupt therapy if reversible posterior leukoencephalopathy syndrome occurs; resume only when resolved and if the benefit outweighs the risk. Elderly. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 3 weeks after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 6 days after the last dose).

Pharmacologic Class:

Kinase inhibitor.

Interactions:

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 Adults. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort). May inhibit P-gp, BCRP and BSEP substrates.

Adverse Reactions:

Abdominal pain, rash, constipation, headache, dry skin, arterial occlusion, fatigue, hypertension, pyrexia, arthralgia, nausea, diarrhea, increased lipase, vomiting, myalgia, extremity pain; myelosuppression.

Generic Availability:

NO

How Supplied:

Tabs 15mg—30, 60; 30mg, 45mg—30