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 CPK levels prior to initiation and clinically thereafter. Obtain CPK and serum creatinine levels at least weekly (in patients with musculoskeletal adverse reactions with concurrent CPK elevation >2.5xULN) until resolution of signs/symptoms. 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, musculoskeletal adverse reactions.
Note:
To report exposure to Daurismo during pregnancy, call Pfizer at (800) 438-1985.
Drug Elimination:
Renal (49%), fecal (42%).
Half-life: 17.4 hours.
Geometric mean apparent clearance: 6.45 L/h following 100 mg once daily dosing in patients with hematologic malignancies.
Generic Drug Availability:
NO
How Supplied:
Tabs 25mg—60; 100mg—30
