Leukemias, lymphomas, and other hematologic cancers:
Indications for: SPRYCEL
Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib in adults. Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy in adults. Newly-diagnosed Ph+ ALL in combination with chemotherapy in children.
Swallow whole. Chronic phase CML: 100mg once daily; may increase to 140mg once daily if unable to achieve hematologic or cytogenic response. Continue until disease progression or unacceptable toxicity. Accelerated phase CML, myeloid or lymphoid blast CML, Ph+ ALL: 140mg once daily; may increase to 180mg once daily. Avoid concomitant strong CYP3A4 inhibitors; if unavoidable, consider reducing Sprycel dose (see full labeling). Avoid concomitant strong CYP3A4 inducers; if unavoidable, consider increasing Sprycel dose (monitor). Dose adjustments for toxicity: see full labeling.
Swallow whole. <1yr or <10kg: not recommended. ≥1yr: Chronic phase CML: 10–<20kg: initially 40mg once daily; may increase to max 50mg/day. 20–<30kg: initially 60mg once daily; may increase to max 70mg/day. 30–<45kg: initially 70mg once daily; may increase to max 90mg/day. ≥45kg: initially 100mg once daily; may increase to max 120mg/day. Continue until disease progression or unacceptable toxicity. Ph+ ALL (initiate on or before Day 15 of induction chemotherapy when diagnosis confirmed): 10–<20kg: 40mg once daily; 20–<30kg: 60mg once daily; 30–<45kg: 70mg once daily; ≥45kg: 100mg once daily. Continue for max 2yrs. Both: recalculate dose every 3 months based on changes in body weight. Avoid concomitant strong CYP3A4 inhibitors; if unavoidable, consider reducing Sprycel dose (see full labeling). Avoid concomitant strong CYP3A4 inducers; if unavoidable, consider increasing Sprycel dose (monitor). Dose adjustments for toxicity: see full labeling.
Risk of severe myelosuppression. Obtain CBCs every 2 weeks for 12 weeks, then every 3 months thereafter (chronic phase CML) or weekly for the first 2 months, then monthly thereafter (advanced phase CML or Ph+ ALL). In children with Ph+ ALL on combination chemotherapy, obtain CBCs before starting each block of chemotherapy and as clinically indicated; do every 2 days until recovery during consolidation. Monitor for signs/symptoms of cardiac dysfunction; treat appropriately if occur. Congenital long QT syndrome. Proarrhythmic conditions. Cumulative high-dose anthracycline therapy. Hypokalemia, hypomagnesemia; correct electrolyte imbalances before starting and during therapy. Monitor for pleural effusions. Increased risk of pulmonary arterial hypertension (PAH); evaluate for signs/symptoms of underlying cardiopulmonary disease before and during treatment; permanently discontinue if occurs. Permanently discontinue if severe skin reactions (eg, Stevens-Johnson syndrome) occur. Increased risk of tumor lysis syndrome in advanced stage disease and/or high tumor burden. Maintain adequate hydration. Correct uric acid levels before therapy and monitor electrolytes. Hepatic impairment. Elderly. Embryo-fetal toxicity. Pregnancy: avoid. Advise females of reproductive potential to use effective contraception during and for 30 days after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).
May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole), grapefruit juice; see Adults. May be antagonized by strong CYP3A4 inducers (eg, rifampin), St. John's wort; see Adults. Separate dosing of antacids by at least 2hrs; H2 blockers, proton pump inhibitors: not recommended. Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants. Caution with antiarrhythmics or other drugs that may lead to QT prolongation.
Myelosuppression, fluid retention, diarrhea, headache, dyspnea, musculoskeletal pain, rash, fatigue, nausea, severe hemorrhage (eg, CNS, GI); QT prolongation, cardiac events, PAH, severe skin reactions. Also in children: effects on bone growth and development (monitor).
Generic Drug Availability:
Tabs 20mg, 50mg, 70mg—60; 80mg, 100mg, 140mg—30