Tazatred Dosage/Direction for Use

The recommended starting dosage of TAZATRED (dasatinib) for chronic phase CML is 100 mg administered orally once daily (QD), either in the morning or in the evening. The recommended starting dosage of TAZATRED for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL is 140 mg/day administered orally in two divided doses (70 mg twice daily [BID]), one in the morning and one in the evening. Tablets should not be crushed or cut; they should be swallowed whole. TAZATRED can be taken with or without a meal.
In clinical studies, treatment with TAZATRED was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment after the achievement of a complete cytogenetic response (CCyR) has not been investigated.
Dose Modification: Concomitant Strong CYP3A4 inducers: The use of concomitant strong CYP3A4 inducers may decrease dasatinib plasma concentrations and should be avoided (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital). St. John's Wort may decrease dasatinib plasma concentrations unpredictably and should be avoided. If patients must be coadministered a strong CYP3A4 inducer, based on pharmacokinetic studies, a TAZATRED dose increase should be considered.
If the dose of TAZATRED is increased, the patient should be monitored carefully for toxicity [see Interactions].
Concomitant Strong CYP3A4 inhibitors: CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) may increase dasatinib plasma concentrations. Grapefruit juice may also increase plasma concentrations of dasatinib and should be avoided.
Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. If TAZATRED must be administered with a strong CYP3A4 inhibitor, a dose decrease to 20 mg daily should be considered. If 20 mg/day is not tolerated, either the strong CYP3A4 inhibitor must be discontinued, or TAZATRED should be stopped until treatment with the inhibitor has ceased. When the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the TAZATRED dose is increased [see Interactions].
Dose Escalation: In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 140 mg once daily (chronic phase CML) or 100 mg twice daily (advanced phase CML and Ph+ ALL) was allowed in patients who did not achieve a hematologic or cytogenetic response at the recommended starting dosage.
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.)

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Non-hematological adverse reactions: If a severe non-hematological adverse reaction develops with TAZATRED 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.