IMPORTANT SAFETY INFORMATION AND INDICATION
IMPORTANT SAFETY INFORMATION AND INDICATION
WARNING: EMBRYO-FETAL TOXICITY: DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals. Conduct pregnancy testing in females of reproductive potential prior to initiation of DAURISMO treatment. Advise females of reproductive potential to use effective contraception during treatment with DAURISMO and for at least 30 days after the last dose. Advise males of the potential risk of DAURISMO exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with DAURISMO and for at least 30 days after the last dose to avoid potential drug exposure.
Blood Donation: Advise patients not to donate blood or blood products while taking DAURISMO and for at least 30 days after the last dose, because their blood or blood products might be given to a female of reproductive potential.
QTc Interval Prolongation: Patients treated with DAURISMO can develop QTc prolongation and ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia. Of the 98 evaluable patients treated with DAURISMO 100 mg in combination with low-dose cytarabine in the clinical trial, 5% were found to have a QTc interval greater than 500 ms and 4% of patients had an increase from baseline QTc greater than 60 ms. The clinical trial excluded patients with baseline QTc of greater than 470 ms or with a history of long QT syndrome or uncontrolled cardiovascular disease. Monitor electrocardiograms (ECGs) and electrolytes. Concomitant use of DAURISMO with drugs known to prolong the QTc interval and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. In patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring is recommended. Interrupt DAURISMO if QTc interval is >500 ms and discontinue permanently for patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Adverse Reactions: Most common adverse reactions associated with DAURISMO (incidence ≥20%) were anemia (43%), fatigue (36%), hemorrhage (36%), febrile neutropenia (31%), musculoskeletal pain (30%), edema (30%), thrombocytopenia (30%), nausea (29%), dyspnea (23%), decreased appetite (21%), dysgeusia (21%), mucositis (21%), constipation (20%), and rash (20%).
Drug Interactions: Co-administration with strong CYP3A4 inhibitors increased DAURISMO plasma concentrations, which may increase the risk of adverse reactions including QTc interval prolongation. Consider alternative therapies that are not strong CYP3A4 inhibitors during treatment with DAURISMO and monitor patients for increased risk of adverse reactions including QTc interval prolongation. Strong and moderate CYP3A4 inducers should be avoided due to decreased DAURISMO plasma concentrations, which may reduce efficacy. If concomitant use of moderate CYP3A4 inducers cannot be avoided, increase the DAURISMO dosage to 200 mg once daily (if the patient is taking 100 mg) and 100 mg once daily (if the patient is taking 50 mg) as tolerated. Co-administration of DAURISMO with QTc-prolonging drugs may increase the risk of QTc interval prolongation. Avoid co-administration of QTc-prolonging drugs with DAURISMO or replace with alternative therapies. If co-administration of a QTc-prolonging drug is unavoidable, monitor patients for increased risk of QTc interval prolongation.
Lactation: Because of the potential for serious adverse reactions from DAURISMO in a breastfed child, advise women who are taking DAURISMO not to breastfeed or provide breast milk to infants or children during treatment and for at least 30 days after the last dose.
Renal Impairment: No dosage modification is recommended for patients with mild to severe renal impairment. Monitor patients with severe renal impairment (eGFR 15 to 29 mL/min) for increased risk of adverse reactions, including QTc interval prolongation, due to increased glasdegib concentrations.
DAURISMO is a hedgehog pathway inhibitor indicated, in combination with low-dose cytarabine, for the treatment of newly diagnosed acute myeloid leukemia (AML) in adult patients who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.