Leukemias, lymphomas, and other hematologic cancers:

Indications for: ICLUSIG

Treatment of adults with chronic phase (CP) chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors. Treatment of adults with accelerated phase (AP) or blast phase (BP) CML or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other kinase inhibitors are 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 CP-CML.

Adult Dosage:

Swallow whole. ≥18yrs: (CP-CML): initially 45mg once daily with a reduction to 15mg upon achieving ≤1% BCR-ABL1IS; if loss of response occurs, may re-escalate to previously tolerated dosage of 30mg or 45mg; (AP-CML, BP-CML, Ph+ ALL): initially 45mg once daily; consider reducing dose in AP-CML if major cytogenetic response achieved. Consider discontinuing if no response occurred by 3 months. Concomitant strong CYP3A inhibitors (if unavoidable): reduce Iclusig dose (see full labeling). Concomitant hepatic impairment: reduce to 30mg once daily. Dose modifications for adverse reactions: see full labeling.

Children Dosage:

<18yrs: not established.

Boxed Warning:

Arterial occlusive events. Venous thromboembolic events. Heart failure. Hepatotoxicity.

ICLUSIG Warnings/Precautions:

Risk of venous thromboembolic and arterial occlusive events (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, hypercholesterolemia); monitor and interrupt or discontinue based on recurrence/severity. Monitor for heart failure; interrupt or discontinue if new or worsening condition occurs. Monitor LFTs at baseline, then at least monthly or as needed; interrupt or discontinue based on recurrence/severity. Monitor BP at baseline, as clinically needed and manage appropriately; 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; interrupt, resume, or discontinue based on severity. Increased toxicity in newly diagnosed chronic phase CML: not recommended. Conduct eye exams at baseline and periodically during treatment. Monitor for symptoms of neuropathy, hemorrhage, cardiac arrhythmias, or fluid retention and manage as clinically indicated; interrupt, resume at same or reduced dose, or discontinue based on recurrence/severity. Obtain CBCs every 2 weeks for the first 3 months, then monthly or as indicated; if ANC <1×109/L or platelets <50×109/L, interrupt until ANC ≥1.5×109/L and platelets ≥75×109/L, then resume at same or reduced dose. Tumor lysis syndrome: ensure adequate hydration and treat uric levels prior to therapy. Impaired wound healing: withhold for ≥1 week prior to elective surgery; do not give for ≥2 weeks after major surgery and until adequate healing. Permanently discontinue if GI perforation occurs. Interrupt therapy if reversible posterior leukoencephalopathy syndrome occurs. Hepatic impairment. 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).

ICLUSIG Classification:

Kinase inhibitor.

ICLUSIG Interactions:

Avoid concomitant strong CYP3A inhibitors (eg, ketoconazole); if unavoidable, reduce Iclusig dose. Avoid concomitant strong CYP3A inducers unless the benefit outweighs the risk (eg, rifampin). May inhibit P-gp, BCRP and BSEP substrates.

Adverse Reactions:

Rash and related conditions, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction, arterial occlusive events, decreased platelet count, decreased neutrophil cell count, decreased white blood cell.

Generic Drug Availability:

NO

How Supplied:

Tabs 15mg—30, 60; 10mg, 30mg, 45mg—30