DOSAGE AND ADMINISTRATION
The recommended dosage of SPRYCEL (dasatinib) is 140 mg/day administered orally in two divided doses (70 mg twice daily [BID]), one in the morning and one in the evening with or without a meal. Tablets should not be crushed or cut; they should be swallowed whole.
In clinical studies, treatment with SPRYCEL 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 has not been investigated.
Dose Modification
Dose increase or reduction of 20-mg increments per dose is recommended based on individual safety and tolerability.
CYP3A4 inducers such as rifampin may decrease SPRYCEL plasma concentrations. Coadministration of SPRYCEL with rifampin resulted in a decrease in the mean Cmax and AUC of dasatinib by 81% and 82%, respectively (a 5-fold decrease in SPRYCEL plasma concentrations). Selection of an alternate concomitant medication with no or minimal enzyme induction potential is recommended. If SPRYCEL must be administered with a CYP3A4 inducer, a dose increase should be considered.
If the dose of SPRYCEL is increased, the patient should be monitored carefully for toxicity (see CLINICAL PHARMACOLOGY and PRECAUTIONS: Drug Interactions). St. John's wort may decrease SPRYCEL plasma concentrations unpredictably. Patients receiving SPRYCEL should not take St. John's wort concomitantly.
CYP3A4 inhibitors such as ketoconazole may increase SPRYCEL plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. If SPRYCEL must be administered with a strong CYP3A4 inhibitor, a dose decrease to 20–40 mg daily should be considered (see CLINICAL PHARMACOLOGY and PRECAUTIONS: Drug Interactions).
Dose Escalation
In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 90 mg BID (chronic phase CML) or 100 mg BID (advanced phase CML and Ph+ ALL) was allowed in patients who did not achieve a hematologic or cytogenetic response at the recommended 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 6.
Table 6: Dose Adjustments for Neutropenia and Thrombocytopenia |
|---|
| *ANC: absolute neutrophil count |
Chronic Phase CML
(starting dose 70 mg BID) | ANC* <0.5 × 109/L
and/or
Platelets <50 × 109/L | - Stop SPRYCEL until ANC ≥1.0 × 109/L and platelets ≥50 × 109/L.
- Resume treatment with SPRYCEL at the original starting dose.
- If platelets <25 × 109/L and/or recurrence of ANC <0.5 × 109/L for >7 days, repeat Step 1 and resume SPRYCEL at a reduced dose of 50 mg BID (second episode) or 40 mg BID (third episode).
|
Accelerated Phase CML,
Blast Phase CML and
Ph+ ALL
(starting dose 70 mg BID) | ANC <0.5 × 109/L
and/or
Platelets <10 × 109/L | - Check if cytopenia is related to leukemia (marrow aspirate or biopsy).
- If cytopenia is unrelated to leukemia, stop SPRYCEL until ANC ≥1.0 × 109/L and platelets ≥20 × 109/L and resume at the original starting dose.
- If recurrence of cytopenia, repeat Step 1 and resume SPRYCEL at a reduced dose of 50 mg BID (second episode) or 40 mg BID (third episode).
- If cytopenia is related to leukemia, consider dose escalation to 100 mg BID.
|
Non-hematological adverse reactions
If a severe non-hematological adverse reaction develops with SPRYCEL 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.
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