Phyrago Dosage

2.1 Recommended Dosage in Adult Patients

The recommended starting dosage of PHYRAGO for chronic phase CML in adults is 100 mg administered orally once daily. The recommended starting dosage of PHYRAGO for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL in adults is 140 mg administered orally once daily. Swallow PHYRAGO whole. Do not crush, cut, or chew the tablets. PHYRAGO can be taken with or without a meal, either in the morning or in the evening.

Dose Modifications

Strong CYP3A4 Inducers

Avoid the use of concomitant strong CYP3A4 inducers. If patients must be coadministered a
strong CYP3A4 inducer, consider a PHYRAGO dose increase. If the dose of PHYRAGO is increased, monitor the patient carefully for toxicity.

Strong CYP3A4 Inhibitors

Avoid the use of concomitant strong CYP3A4 inhibitors and grapefruit juice. Recommend selecting an alternate concomitant medication with no or minimal enzyme inhibition potential, if possible. If PHYRAGO must be administered with a strong CYP3A4 inhibitor, consider a dose decrease to:

• 40 mg daily for patients taking PHYRAGO 140 mg daily.
• 20 mg daily for patients taking PHYRAGO 100 mg daily.
• 20 mg daily for patients taking PHYRAGO 70 mg daily.

For patients taking PHYRAGO 60 mg or 40 mg daily, consider interrupting PHYRAGO until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before reinitiating PHYRAGO.

These reduced doses of PHYRAGO 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 PHYRAGO is not tolerated after dose reduction, either discontinue the strong CYP3A4 inhibitor or interrupt PHYRAGO until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before the PHYRAGO dose is increased.

Antacids

Avoid concomitant use of PHYRAGO with antacids. If concomitant use of an antacid cannot be avoided, administer the antacid at least 2 hours prior to or 2 hours after the dose of PHYRAGO​.

Dose Escalation in Adults with CML and Ph+ ALL, and Pediatric Patients with CML

For adult patients with CML and Ph+ ALL, consider dose escalation to 140 mg once daily (chronic phase CML) or 180 mg once daily (advanced phase CML and Ph+ ALL) in patients who do not achieve a hematologic or cytogenetic response at the recommended starting dosage.

Dosage 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 for adult and pediatric patients are summarized in Table 1.

*ANC: absolute neutrophil count

Non-Hematologic Adverse Reactions
For adults with Ph+ CML and ALL, and pediatric patients with Ph+ CML, if a severe non-hematologic adverse reaction develops with PHYRAGO use, treatment must be withheld until the adverse reaction has resolved or improved. Thereafter, treatment can be resumed as appropriate at a reduced dose depending on the severity and recurrence.

Duration of Treatment

In clinical studies, treatment with dasatinib in adults with chronic phase CML 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 cytogenetic response (including complete cytogenetic response [CCyR]) or major molecular response (MMR and MR4.5) has not been established.

PHYRAGO is a hazardous product. Follow applicable special handling and disposal procedures.1

Pediatric use information is approved for Bristol-Myers Squibb Company’s SPRYCEL (dasatinib) tablets. However, due to Bristol-Myers Squibb Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.