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.

Limitations of Use:

Not studied in those with severe renal impairment or moderate-to-severe hepatic impairment.

Adult:

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. Dose modifications: see full labeling.

Children:

Not established.

Boxed Warning:

Embryo-fetal toxicity.

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. Pregnancy: avoid. Nursing mothers: not recommended (during and for ≥30 days after the last dose).

Pharmacologic Class:

Hedgehog pathway inhibitor.

Interactions:

Potentiated by strong CYP3A4 inhibitors; consider alternative therapies or monitor for increased adverse reactions. Antagonized by strong CYP3A4 inducers; avoid concomitant use. 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.

Generic Availability:

NO

How Supplied:

Tabs 25mg—60; 100mg—30