Sprycel 80mg Tablets (Dasatinib)

Adult dose

The recommended initial dose of this medicine for chronic-phase chronic myeloid leukemia is 100 mg orally once daily. The recommended initial dose for accelerated-phase or myeloid or lymphoid blast-phase chronic myeloid leukemia, and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is 140 mg orally once daily. This medicine may be taken in the morning or evening, regardless of meals. If this medicine must be administered concomitantly with a strong CYP3A4 inhibitor, dose reduction should be considered as follows. ㆍ Patients receiving this medicine 140 mg once daily: 40 mg once daily ㆍ Patients receiving this medicine 100 mg once daily: 20 mg once daily ㆍ Patients receiving this medicine 70 mg once daily: 20 mg once daily For patients receiving this medicine 60 mg or 40 mg once daily, discontinuation of this medicine should be considered until the CYP3A4 inhibitor is discontinued. If the reduced dose is not tolerated, this medicine should be discontinued until the strong CYP3A4 inhibitor is discontinued or inhibitor treatment is completed. After discontinuation of the strong inhibitor, an approximately 1-week washout period should be allowed before increasing the dose of this medicine. In clinical studies of adults with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), patients who did not achieve a hematologic and cytogenetic response at the recommended initial dose were permitted to increase the dose to 140 mg once daily (patients with chronic-phase chronic myeloid leukemia) or 180 mg once daily (patients with accelerated-phase or blast-phase chronic myeloid leukemia and patients with Philadelphia chromosome-positive acute lymphoblastic leukemia). In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study treatment. Dose adjustments are recommended as follows. Dose adjustment for neutropenia and thrombocytopenia in adults Chronic-phase chronic myeloid leukemia (chronic phase CML): Start treatment at a dose of 100 mg once daily Absolute neutrophil count below 0.5 x 109/L or platelet count below 50 x 109/L ∙ Interrupt treatment with this medicine until the absolute neutrophil count is at least 1.0 x 109/L and the platelet count is at least 50 x 109/L ∙ If recovery occurs within 7 days or less, resume treatment with this medicine at the starting dose ∙ If a platelet count below 25 x 109/L or an absolute neutrophil count below 0.5 x 109/L for more than 7 days recurs, repeat step 1; on the second recurrence, resume treatment at a reduced dose of 80 mg once daily. On the third recurrence, further reduce the dose to 50 mg once daily in newly diagnosed patients, and discontinue this medicine in patients resistant or intolerant to prior therapy including imatinib. Accelerated phase or blast phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia: Start treatment at a dose of 140 mg once daily Absolute neutrophil count below 0.5 x 109/L or platelet count below 10 x 109/L ∙ Determine whether the cytopenia is related to leukemia (bone marrow aspiration or biopsy). ∙ If the cytopenia is not related to leukemia, interrupt treatment with this medicine until the absolute neutrophil count is at least 1.0 x 109/L and the platelet count is at least 20 x 109/L, then resume treatment at the starting dose. ∙ If the cytopenia recurs, repeat step 1; on the second recurrence, resume treatment with this medicine at a reduced dose of 100 mg once daily, and on the third recurrence at a reduced dose of 80 mg once daily. ∙ If the cytopenia is related to leukemia, increase the dose to 180 mg once daily. In adult patients with Ph+ CML and ALL, if a serious nonhematologic adverse reaction occurs with this medicine, treatment should be withheld until the reaction resolves or improves. Thereafter, treatment may be resumed at a reduced dose, as appropriate, depending on the symptoms and recurrence of the reaction.

Child dose

In pediatric patients, the recommended initial dose is based on body weight. This drug is administered orally once daily, with or without food. Recalculate the dose every 3 months or more frequently as needed based on changes in body weight. Recommended initial daily dose of this drug for pediatric patients Not recommended for patients weighing less than 10kg. Body weight 10kg or more and less than 20kg: daily dose 40mg Body weight 20kg or more and less than 30kg: daily dose 60mg Body weight 30kg or more and less than 45kg: daily dose 70mg Body weight 45kg or more: daily dose 100mg In pediatric patients with Ph+ ALL, treatment with this drug should be initiated on or before day 15 of induction chemotherapy. For pediatric patients with CML who do not achieve a hematologic or cytogenetic response with the recommended initial dose, the following dose increases are recommended. Dose escalation for pediatric patients with CML (tablets, maximum daily dose) Initial dose 40mg: increase to 50mg Initial dose 60mg: increase to 70mg Initial dose 70mg: increase to 90mg Initial dose 100mg: increase to 120mg Dose escalation of this drug is not recommended when it is administered in combination with chemotherapy to pediatric patients with Ph+ ALL. Dose adjustments for neutropenia and thrombocytopenia in pediatric patients with chronic-phase CML (tablets, maximum daily dose) Initial dose 40mg: first dose reduction 20mg: second dose reduction ** Initial dose 60mg: first dose reduction 40mg: second dose reduction 20mg Initial dose 70mg: first dose reduction 60mg: second dose reduction 50mg Initial dose 100mg: first dose reduction 80mg: second dose reduction 70mg 1. If cytopenia persists for more than 3 weeks, determine whether it is associated with leukemia (bone marrow aspiration or biopsy). 2. If the cytopenia is not related to leukemia, discontinue this drug until ANC*≥1.0× 109/L and platelets ≥75× 109/L, then resume treatment at the starting dose or a reduced dose. 3. If cytopenia recurs, repeat bone marrow aspiration/biopsy and resume treatment with this drug at a reduced dose. *ANC: absolute neutrophil count **Lower-strength tablets are unavailable In pediatric patients with chronic-phase CML, if grade 3 or higher neutropenia or thrombocytopenia recurs during complete hematologic response (CHR), treatment with this drug should be interrupted and may subsequently be resumed at a reduced dose. Temporary dose reductions may be made as needed for moderate cytopenia and disease response. In pediatric patients with ALL, if the next treatment block is delayed by 14 days or more due to neutropenia or thrombocytopenia, this drug should be interrupted and resumed at the same dose when the next treatment block begins. If neutropenia or thrombocytopenia persists and the next treatment block is delayed by an additional 7 days, a bone marrow examination should be performed to assess cellularity and the percentage of blasts. If bone marrow cellularity is less than 10%, treatment with this drug should be interrupted until the absolute neutrophil count exceeds 500/μL(0.5 x 109/L); treatment may be resumed at the usual dose. If bone marrow cellularity exceeds 10%, resumption of treatment with this drug may be considered. In pediatric patients with Ph+ CML, if serious nonhematologic adverse reactions occur with this drug, treatment should be withheld until the reaction resolves or improves. Treatment may then be resumed at a reduced dose, as appropriate, depending on the symptoms and recurrence of the reaction. In pediatric patients with Ph+ ALL, dose adjustment for grade 2 nonhematologic toxicity is as follows. If a grade 3 or higher nonhematologic adverse reaction occurs, excluding abnormal liver function tests, treatment should be interrupted and resumed at a reduced dose once the adverse reaction has resolved to grade 1 or lower. If direct bilirubin increases to more than 5 times the upper limit of normal (ULN), treatment should be interrupted until the level returns to baseline or below grade 1. If AST/ALT increases to more than 15 times the ULN, treatment should be interrupted until the levels return to baseline or below grade 1. If the above liver function test abnormalities recur, reduce the dose of this drug if the adverse reaction recurs after re-administration. Dose adjustments for nonhematologic adverse reactions in pediatric patients (tablets, maximum daily dose) Initial dose 40mg: first dose reduction 20mg: second dose reduction ** Initial dose 60mg: first dose reduction 40mg: second dose reduction 20mg Initial dose 70mg: first dose reduction 60mg: second dose reduction 50mg Initial dose 100mg: first dose reduction 80mg: second dose reduction 70mg 1. If grade 2 nonhematologic toxicity occurs and does not resolve despite treatment of the symptoms, consider interrupting this drug. When the adverse reaction resolves to grade 1 or lower, resume treatment at the starting dose. If the adverse reaction recurs, resume treatment at a reduced dose. 2. If grade 3 nonhematologic toxicity occurs, interrupt this drug until it resolves to grade 1 or lower, then resume treatment at a reduced dose. 3. If direct bilirubin increases to more than 5 times the upper limit of normal or AST/ALT increases to more than 15 times the upper limit of normal, interrupt this drug until the abnormality resolves to below grade 1, then resume treatment at the starting dose. If the adverse reaction recurs, resume treatment at a reduced dose. **Lower-strength tablets are unavailable

This medication can cause serious harm to the fetus if taken during pregnancy; therefore, it should not be used by pregnant women. Women of childbearing potential must avoid pregnancy during treatment and use appropriate contraception. Patients allergic to the ingredients of this medication or with genetic lactose intolerance should not take this medication. Patients taking platelet-function inhibiting drugs or anticoagulants should exercise caution, as there may be an increased risk of bleeding when using this medication. This medication can prolong the QT interval related to heart rhythms, and caution should be exercised in patients with hypokalemia, hypomagnesemia, congenital long QT syndrome, or those taking antiarrhythmic drugs. Patients with impaired liver function should use this medication with increased caution, as its metabolism may be affected. This drug can cause serious side effects such as pulmonary arterial hypertension, so lung function should be monitored before and during treatment, and any symptoms that arise should be reported to a doctor immediately. Patients who are carriers of the hepatitis B virus must be tested before taking this medication and should be monitored periodically during treatment for signs of reactivation. This medication can cause bone marrow suppression resulting in anemia, thrombocytopenia, leukopenia, etc., so regular blood tests are necessary; dosage adjustments or temporary cessation may be needed if abnormalities are found. Fluid retention may occur, so if symptoms such as swelling or breathing difficulties appear, the healthcare provider should be informed immediately, and appropriate treatment should be administered if necessary. If severe skin reactions occur, the medication should be discontinued immediately, and consultation with healthcare providers is advised. This drug has many interactions with other medications, so particularly if taking medications metabolized by the liver, antacids, or anticoagulants, inform the physician or pharmacist. Elderly patients may experience side effects such as fatigue, breathing difficulties, or heart function abnormalities more frequently when taking this medication, so careful observation is necessary. Serious bone marrow suppression and bleeding may occur in the event of an overdose, so the prescribed dosage should be strictly adhered to, and in case of overdose, the hospital should be visited immediately. This medication should be stored at room temperature (15-30°C), and broken or damaged tablets pose a risk of skin exposure; it is advisable to wear gloves when handling. Pregnant women should take precautions to avoid exposure to broken tablets.

• Bone marrow suppression
• bleeding
• fluid retention
• QT prolongation
• severe skin reactions
• congestive heart failure
• left ventricular dysfunction
• myocardial infarction
• pulmonary hypertension
• effects on growth and development

This medication should be stored in a tightly sealed container to protect it from air and moisture. The ideal storage temperature is a cool place between 15°C and 30°C.

Appearance

White to grayish-white, convex, triangular film-coated tablet

Package unit

30 tablets/PTP