LuciDasa 50 (Dasatinib)

Acute Lymphoblastic Leukemia (ALL)

Indicated for treatment of Philadelphia chromosome-positive (Ph+) ALL in adults with resistance or intolerance to prior therapy

Initial, 140 mg PO daily; may increase to 180 mg PO daily if hematologic or cytogenetic response not achieved with initial dosage

Chronic Myeloid Leukemia (CML)

Newly diagnosed CML in chronic phase

• 100 mg PO daily; may increase to 140 mg PO daily if hematologic or cytogenetic response not achieved with initial dosage
• Therapy was continued until disease progression or until no longer tolerated in clinical studies

Previously treated CML

• Indicated for treatment of chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML in adults with resistance or intolerance to prior therapy including imatinib
• Initial, 140 mg PO daily; may increase to 180 mg PO daily if hematologic or cytogenetic response not achieved with initial dosage

Dosage Modifications

Myelosuppression

• Chronic phase CML (100 mg/day starting dose)

  • ANC <0.5 x 10^9/L or platelets <50 x 10^9/L: Hold until ANC ≥1 x 10^9/L and platelets ≥50 x 10^9/L; resume at original starting dose if recovery occurs in ≤7 days
  • Platelets <25 x 10^9/L or recurrence of ANC <0.5 x 10^9/L for >7 days: Hold until ANC ≥1 x 10^9/L and platelets ≥50 x 10^9/L; resume at reduced dosage of 80 mg PO daily for second episode and 50 mg PO daily (newly diagnosed CML) or discontinue (previously treated CML) for third episode

• Ph+ ALL and accelerated or blast phase CML (140 mg/day starting dose)

  • Perform bone marrow assessment to determine if cytopenia is related to leukemia
  • Hold until ANC ≥1 x 10^9/L and platelets ≥20 x 10^9/L and resume at original starting dose if cytopenia is unrelated to leukemia
  • If cytopenia recurs, repeat bone marrow assessment and resume at reduced dose of 100 mg PO daily for second episode or 80 mg PO daily for third episode
  • If cytopenia is related to leukemia, consider dose escalation to 180 mg PO daily

Non-hematologic toxicity

• Severe toxicity

  • Hold until toxicity has resolved or improved
  • Resume as appropriate at reduced dose depending on severity and recurrence

Renal impairment

• CrCl 21.6-342.3 mL/min: No significant impact on pharmacokinetics

Hepatic impairment

• Mild (Child Pugh A): No data
• Moderate (Child Pugh B): No dosage adjustment guidance provided by manufacturer; exposure decreased by 8% compared with normal liver function
• Severe (Child Pugh C): No dosage adjustment guidance provided by manufacturer; exposure decreased by 28% compared with normal liver function

Strong CYP3A4 inducers

• Avoid coadministration
• If coadministration of strong CYP3A4 inducer is unavoidable, consider increasing dasatinib dose and monitor for toxicity

Strong CYP3A4 inhibitors

• Avoid coadministration and select alternate concomitant medication with no or minimal enzyme inhibition potential, if possible

• Dosage adjustment for use with strong CYP3A4 inhibitor if coadministration cannot be avoided

  • Current dose 140 mg/day: Decrease to 40 mg PO daily
  • Current dose 100 mg/day or 70 mg/day: Decrease to 20 mg PO daily
  • Current dose 60 or 40 mg/day: Consider holding therapy until inhibitor is discontinued
  • If dasatinib is not tolerated after dose reduction, either discontinue strong CYP3A4 inhibitor or interrupt dasatinib until inhibitor is discontinued
  • Allow a washout period of ∼1 week after inhibitor is stopped before reinitiating or increasing dasatinib dose