Sprycel Tablet 100 mg (Dasatinib)

Adult dose

1. Recommended Dosage for Adults The recommended starting dose of this drug for chronic-phase chronic myeloid leukemia is 100mg orally once daily. The recommended starting dose of this drug for accelerated-phase or myeloid or lymphoid blast-phase chronic myeloid leukemia, and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is 140mg orally once daily. Swallow this drug whole without crushing or cutting it. This drug may be taken in the morning or evening, with or without food. 3. Dose Modifications 1) Concomitant administration with strong CYP3A4 inducers: Concomitant administration with strong CYP3A4 inducers should be avoided because it may decrease plasma concentrations of dasatinib. (dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) St. John's Wort should be avoided because it may unexpectedly decrease plasma concentrations of dasatinib. If a patient must receive a strong CYP3A4 inducer concomitantly, an increase in the dose of this drug should be considered based on pharmacokinetic studies. If the dose of this drug must be increased, the patient should be monitored closely for toxicity. 2) Concomitant administration with strong CYP3A4 inhibitors: Concomitant administration with strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) and grapefruit juice should be avoided. If possible, selection of an alternative concomitant medication with no or minimal potential for enzyme inhibition is recommended. If this drug must be administered with a strong CYP3A4 inhibitor, dose reduction should be considered as follows. ㆍ Patients receiving 140mg of this drug once daily: 40mg once daily ㆍ Patients receiving 100mg of this drug once daily: 20mg once daily ㆍ Patients receiving 70mg of this drug once daily: 20mg once daily For patients receiving 60mg or 40mg of this drug once daily, discontinuation of this drug should be considered until the CYP3A4 inhibitor is discontinued. These dose reductions are expected to adjust exposure to within the range of the area under the plasma concentration-time curve (AUC) observed when this drug was not administered concomitantly with a CYP3A4 inhibitor. However, no clinical studies of dose adjustment have been conducted in patients receiving strong CYP3A4 inhibitors. If the patient does not tolerate this drug after dose reduction, this drug should be discontinued until the strong CYP3A4 inhibitor is discontinued or inhibitor treatment is completed. When a strong inhibitor is discontinued, an approximately 1-week washout period should be allowed before increasing the dose of this drug (see ‘6. Interactions’ under Precautions for Use). 4. Dose Escalation In clinical studies in adults with chronic myeloid leukemia (CML) and patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), for patients who did not achieve a hematologic and cytogenetic response at the recommended starting dose, dose escalation to 140mg once daily (for patients with chronic-phase chronic myeloid leukemia) or 180mg once daily (for patients with accelerated-phase or blast-phase chronic myeloid leukemia and patients with Philadelphia chromosome-positive acute lymphoblastic leukemia) was permitted. 5. Dose Adjustment for Adverse Reactions 1) Myelosuppression In clinical studies, myelosuppression was managed by temporary interruption of treatment (dose interruption), dose reduction, or discontinuation of study treatment. Hematopoietic growth factors were used in patients with myelosuppression that was resistant to treatment. Dose adjustments are recommended as shown in Tables 3 and 4 below. Table 3. Dose adjustment for neutropenia and thrombocytopenia in adults Chronic-phase chronic myeloid leukemia (chronic phase CML): Start treatment at a dose of 100mg once daily Absolute neutrophil count less than 0.5 x 109/L or platelet count less than 50 x 109/L ∙ Interrupt treatment with this drug 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 drug at the starting dose ∙ If a platelet count less than 25 x 109/L or an absolute neutrophil count less than 0.5 x 109/L for more than 7 days recurs, repeat Step 1; upon the second recurrence, resume treatment at a reduced dose of 80mg once daily. Upon the third recurrence, further reduce the dose to 50mg once daily in newly diagnosed patients, and discontinue this drug 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 140mg once daily Absolute neutrophil count less than 0.5 x 109/L or platelet count less than 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 drug until the absolute neutrophil count is at least 1.0 x 109/L and the platelet count is at least 20 x 109/L, and resume treatment at the starting dose. ∙ If the cytopenia recurs, repeat Step 1; upon the second recurrence, resume treatment with this drug at a reduced dose of 100mg once daily, and upon the third recurrence, at a reduced dose of 80mg once daily. ∙ If the cytopenia is related to leukemia, increase the dose to 180mg once daily. 2) Nonhematologic Adverse Reactions In adult patients with Ph+ CML and ALL or pediatric patients with Ph+ CML, if a serious nonhematologic adverse reaction occurs with this drug, treatment should be withheld until the reaction resolves or improves. Treatment may then be resumed at a reduced dose, as appropriate, according to the symptoms and recurrence of the reaction. 6. Duration of Treatment In clinical studies, treatment with this drug in adults and pediatric patients with chronic-phase CML continued until disease progression or intolerance occurred. The effect on long-term disease outcomes of discontinuing treatment after a cytogenetic response (complete cytogenetic response, CCyR) or major molecular response (including MMR and MR4.5) has been achieved has not been established.

Child dose

2. Recommended Pediatric Dosage The recommended initial dose in pediatric patients is based on body weight, as shown in Table 1. This drug is administered orally once daily, with or without food. The dose should be recalculated every 3 months or more frequently as needed, according to changes in body weight. This drug must not be crushed, split, or chewed. It must be swallowed whole. In pediatric patients, exposure after taking a crushed tablet was lower than after taking the whole tablet. In pediatric patients with Ph+ ALL, administer this drug in combination with chemotherapy (see Precautions for Use, 4. Adverse Reactions, item 4), and 8. Use in Pediatric Patients). The recommended initial daily dose of this drug for pediatric patients is shown in Table 1. Table 1. Dosage for Pediatric Patients At least 10kg but less than 20kg: 40mg At least 20kg but less than 30kg: 60mg At least 30kg but less than 45kg: 70mg At least 45kg: 100mg * Not recommended for patients weighing less than 10kg. ** In pediatric patients with Ph+ ALL, treatment with this drug should be started on or before Day 15 of induction chemotherapy. 4. Dose Escalation For pediatric patients with CML who do not achieve a hematologic or cytogenetic response at the recommended initial dose, the dose escalation shown in Table 2 below is recommended. Table 2. Dose Escalation for Pediatric Patients with CML Tablet, initial dose 40mg: escalated dose 50mg Tablet, initial dose 60mg: escalated dose 70mg Tablet, initial dose 70mg: escalated dose 90mg Tablet, initial dose 100mg: escalated dose 120mg Dose escalation of this drug is not recommended when it is administered in combination with chemotherapy in pediatric patients with Ph+ ALL. 5. Dose Adjustment Due to Adverse Reactions 1) Myelosuppression Table 4. Dose Adjustment for Neutropenia and Thrombocytopenia in Pediatric Patients with Chronic-Phase CML Dose (tablet, maximum daily dose) 1. If cytopenia persists for more than 3 weeks, determine whether the cytopenia is related to leukemia (bone marrow aspiration or biopsy). 2. If the cytopenia is not related to leukemia, interrupt this drug until ANC*≥1.0× 109/L and platelets are ≥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. 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 *ANC: absolute neutrophil count **No lower-strength tablet available 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 for 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), and may be resumed at the normal dose when treatment is restarted. If bone marrow cellularity exceeds 10%, resumption of treatment with this drug may be considered. 2) Nonhematologic Adverse Reactions For pediatric patients with Ph+ ALL who experience Grade 2 nonhematologic toxicity, refer to Table 5 for dose adjustment. If a nonhematologic adverse reaction of Grade 3 or higher occurs, except for abnormal liver function tests, interrupt treatment and resume at a reduced dose when the adverse reaction resolves to Grade 1 or lower. If direct bilirubin increases to more than 5 times the upper limit of normal (ULN), interrupt treatment until the level returns to baseline or below Grade 1. If AST/ALT increases to more than 15 times the ULN, interrupt treatment until the level returns to baseline or below Grade 1. If the above abnormalities in liver function tests recur, reduce the dose of this drug if the adverse reaction recurs after retreatment with this drug. Dose reduction is recommended as shown in Table 5 below. Table 5. Dose Adjustment for Nonhematologic Adverse Reactions in Pediatric Patients Dose (tablet, maximum daily dose) 1. If Grade 2 nonhematologic toxicity occurs and does not resolve despite treatment of symptoms, consider interrupting this drug. When the adverse reaction resolves to Grade 1 or lower, resume treatment at the starting dose. For recurrent adverse reactions, resume at a reduced dose. 2. If Grade 3 nonhematologic toxicity occurs, interrupt this drug until it resolves to Grade 1 or lower, then resume 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 levels resolve to below Grade 1, then resume at the starting dose. For recurrent adverse reactions, resume at a reduced 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 **No lower-strength tablet available 6. Duration of Treatment In clinical studies, treatment with this drug in adults and pediatric patients with chronic-phase CML continued until disease progression or intolerance occurred. The effect on long-term disease outcomes of discontinuing treatment after achieving a cytogenetic response (complete cytogenetic response (CCyR), major molecular response (MMR), and MR4.5) has not been established. In clinical studies, treatment with this drug in pediatric patients with Ph+ ALL, in addition to the underlying chemotherapy, continued for up to 2 years after confirmation of diagnosis.

This medication can cause serious harm to the fetus if taken during pregnancy, so women of childbearing potential should strictly avoid pregnancy. Patients with allergies to this medication or with certain genetic lactose intolerance should not take this medication. Patients taking medications that affect blood clotting should use this medication cautiously due to the risk of bleeding. Patients with heart function issues or certain electrolyte imbalances should take care due to the risk of side effects. Patients with impaired liver function should be specifically monitored when using this medication. Patients with pulmonary arterial hypertension or at risk of developing it must closely monitor symptoms while on this medication and stop taking it immediately if symptoms occur. Hepatitis B virus carriers should consult with a specialist before and during treatment and carefully monitor for reactivation of the infection. This medication is used to treat hematological cancers, and regular blood tests are necessary since treatment may lead to anemia, thrombocytopenia, and increased infection risk due to bone marrow function suppression. Symptoms such as edema due to fluid retention or pleural effusion can occur, so patients should immediately inform medical professionals if they experience difficulty breathing or swelling. Cardiac side effects such as arrhythmias, heart failure, and myocardial infarction may occur, so patients with a history of heart disease should be especially cautious. This medication can cause QT interval prolongation, so patients at risk for cardiac rhythm abnormalities should correct electrolyte status prior to use and periodically monitor cardiac condition. If severe skin reactions occur, discontinuation of the medication should be immediate, and patients with impaired kidney or liver function should be closely monitored. This medication interacts with some drugs, so patients taking other medications must inform healthcare providers, especially when used with specific antifungals, antibiotics, antacids, and cardiac medications. Breastfeeding women should consider stopping breastfeeding or discontinuing medication as it may be excreted in breast milk. Pediatric patients need regular growth monitoring as this medication can affect growth and bone development. Elderly patients may more commonly experience side effects such as fatigue, difficulty breathing, and bleeding, so careful observation is required. In the case of overdose, severe bone marrow suppression and bleeding may occur, so prescribed dosages must be strictly adhered to, and medical institutions should be visited immediately in case of overdose. This medication should be stored at room temperature between 15 and 30 degrees Celsius, and crushed or broken tablets should avoid skin contact and gloves should be worn during handling.

• 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 sealed container to prevent air or moisture ingress, and it is important to maintain a storage temperature between 15 and 30 degrees Celsius. Proper storage will help maintain the medication's effectiveness.

Appearance

White to off-white, biconvex, oval film-coated tablets, engraved with BMS 100 on one side and 852 on the other side.

Package unit

30 tablets/bottle