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The recommended starting dosage of APO-DASATINIB for accelerated phase CML, or myeloid or lymphoid blast CML, is 140 mg/day administered orally once daily (140 mg QD) either in the morning or in the evening.
The recommended starting dosage of APO-DASATINIB for Ph+ ALL is 140 mg administered orally once daily (140 mg QD) either in the morning or in the evening.
Dosing recommendations in patients with imatinib resistant or intolerant CML and Ph+ ALL are based on the results of two randomized Phase III dose-optimization studies.
APO-DASATINIB can be taken with or without food. Tablets should not be crushed or cut; they should be swallowed whole.
In clinical studies, treatment with dasatinib was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment on long-term disease outcome after the achievement of a complete cytogenetic response (CCyR) or major molecular response (MMR) has not been investigated.
Dose Escalation: In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 140 mg once daily (chronic phase CML) or 180 mg once daily (advanced phase CML and Ph+ ALL) was allowed in patients who did not achieve a hematologic or cytogenetic response at the recommended dosage.
Dose reduction for concomitant use of strong CYP3A4 inhibitors: The concomitant use of strong CYP3A4 inhibitors and grapefruit juice with APO-DASATINIB should be avoided (see Interactions). CYP3A4 inhibitors such as ketoconazole may increase dasatinib plasma concentrations. If possible, an alternative concomitant medication with no or minimal enzyme inhibition potential should be selected. If APO-DASATINIB must be administered with a strong CYP3A4 inhibitor, consider a dose decrease to: 40 mg daily for patients taking APO-DASATINIB 140 mg daily; 20 mg daily for patients taking APO-DASATINIB 100 mg daily; 20 mg daily for patients taking APO-DASATINIB 70 mg daily.
For patients taking APO-DASATINIB 60 mg or 40 mg daily, consider interrupting APO-DASATINIB until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before reinitiating APO-DASATINIB.
The reduced doses of dasatinib are predicted to adjust the area under the curve (AUC) to the range observed without CYP3A4 inhibitors; however, clinical data are not available with these dose adjustments in patients receiving strong CYP3A4 inhibitors. If APO-DASATINIB is not tolerated after dose reduction, either discontinue the strong CYP3A4 inhibitor or stop APO-DASATINIB until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before the APO-DASATINIB dose is increased.
Dose Adjustment for Adverse Reactions: Myelosuppression: In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study therapy. Hematopoietic growth factor has been used in patients with resistant myelosuppression. Guidelines for dose modifications are summarized in Table 1. (See Table 1.)
Click on icon to see table/diagram/imageNon-hematological adverse reactions: If a moderate (Grade 2) non-hematological adverse reaction develops with APO-DASATINIB, treatment should be interrupted until the adverse reaction has resolved or returned to baseline. The same dose should be resumed if this is the first occurrence and the dose should be reduced if this is a recurrent adverse reaction.
If a severe (Grade 3 or 4) non-hematological adverse reaction develops with APO-DASATINIB use, treatment must be withheld until the event has resolved or improved. Thereafter, treatment can be resumed as appropriate at a reduced dose depending on the initial severity of the event. However, in patients diagnosed with pulmonary arterial hypertension (PAH), APO-DASATINIB should be permanently discontinued.
Patients with chronic CML who received 100 mg once daily, dose reduction to 80 mg once daily with further reduction from 80 mg once daily to 50 mg once daily, if needed, is recommended. For adult patients with advanced phase CML or Ph+ ALL who received 140 mg once daily, dose reduction to 100 mg once daily with further reduction from 100 mg once daily to 80 mg once daily, if needed, is recommended.
Pediatrics (<18 years of age): APO-DASATINIB is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.
Hepatic impairment: No clinical pharmacokinetic trials were conducted with a 70 to 100 mg dose of dasatinib in patients with decreased liver function. APO-DASATINIB should be used with caution in patients with moderate to severe hepatic impairment (see Precautions).
Renal impairment: No clinical trials were conducted with dasatinib in patients with decreased renal function (trials excluded patients with serum creatinine concentration >1.5 times the upper limit of the normal range). Since the renal clearance of dasatinib and its metabolites is <4%, a decrease in total body clearance is not expected in patients with renal insufficiency.
