Leukemias, lymphomas, and other hematologic cancers:
Indications for: DAURISMO
In combination with low-dose cytarabine, to treat newly-diagnosed acute myeloid leukemia (AML) in adults ≥75yrs or who have comorbidities that preclude use of intensive induction chemotherapy.
Adult Dosage:
Swallow whole. 100mg once daily on Days 1–28 (in combination with SC cytarabine 20mg twice daily on Days 1–10 of each 28-day cycle), until disease progression or unacceptable toxicity. Treat for minimum of 6 cycles. Concomitant with moderate CYP3A4 inducers (if unavoidable): 200mg once daily (if current dose is 100mg); 100mg once daily (if current dose is 50mg). Dose modifications for adverse reactions: see full labeling.
Children Dosage:
Not established.
Boxed Warning:
Embryo-fetal toxicity.
DAURISMO Warnings/Precautions:
Risk of embryo-fetal death or severe birth defects in pregnant women. Verify pregnancy status within 7 days prior to initiating therapy. Advise females of reproductive potential to use effective contraception during therapy and for ≥30 days after the last dose; male patients should use condoms (even after a vasectomy) during and for ≥30 days after the last dose. Advise patients not to donate blood or blood products during therapy and for ≥30 days after the last dose. Advise male patients not to donate semen during and for ≥30 days after the last dose. Assess CBCs, electrolytes, renal, and hepatic function prior to initiation and at least once weekly for the first month; then monitor electrolytes and renal function once monthly during therapy. Obtain serum creatine kinase levels prior to initiation and clinically thereafter. Monitor ECGs prior to initiation, approx. 1 week after, then once monthly for the next 2 months; in those with congenital long QT syndrome, CHF, electrolyte abnormalities, monitor more frequently. Interrupt if QTc interval >500ms; permanently discontinue if QTc interval prolongation with life-threatening arrhythmia develops. Premature fusion of the epiphyses may occur in pediatrics if exposed. Severe renal impairment (eGFR 15–29mL/min): monitor for increased risk of adverse reactions (eg, QT prolongation). Pregnancy, nursing mothers: not recommended (during and for ≥30 days after the last dose).
DAURISMO Classification:
Hedgehog pathway inhibitor.
DAURISMO Interactions:
Potentiated by strong CYP3A4 inhibitors; consider alternative therapies or monitor for increased adverse reactions. Antagonized by strong or moderate CYP3A4 inducers; avoid; if moderate inducers unavoidable, increase Daurismo dose as tolerated (see Adults). Avoid concomitant drugs known to prolong QTc interval or use alternative therapies; if unavoidable, monitor for increased risk.
Adverse Reactions:
Anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, rash; QT prolongation.
Note:
To report exposure to Daurismo during pregnancy, call Pfizer at (800) 438-1985.
Drug Elimination:
Fecal, renal. Half-life: 17.4 hours.
Generic Drug Availability:
NO
How Supplied:
Tabs 25mg—60; 100mg—30
