• Newly-diagnosed acute myeloid leukemia (AML) in patients who are 75 years old or who have comorbidities that prevent the use of intensive induction chemotherapy (in combination with low-dose cytarabine).

Contraindicated in:

• Blood donation should be avoided during and for 30 days following treatment
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Congenital long QT syndrome, HF, electrolyte abnormalities, or concurrent use of QT interval prolonging medications
• Severe renal impairment
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: QT INTERVAL PROLONGATION, VENTRICULAR ARRHYTHMIAS, atrial fibrillation, bradycardia, chest pain, peripheral edema, tachycardia.

Derm: rash, alopecia.

F and E: hyperkalemia, hypokalemia, hypomagnesemia, hyponatremia.

GI: abdominal pain, constipation, diarrhea, hyperbilirubinemia, ↑liver enzymes, metallic taste, mucositis, nausea, vomiting.

GU: ↓fertility (males), renal impairment.

Hemat: hemorrhage, anemia, neutropenia, thrombocytopenia.

Metab: ↓appetite, ↓weight.

MS: ↑creatine kinase, muscle spasm, pain.

Neuro: dizziness, fatigue, headache.

Resp: cough, dyspnea, pneumonia.

Misc: fever.

Drug-Drug:

• QT interval prolonging drugs may ↑ risk of QT interval prolongation and torsade de pointes; avoid concurrent use.
• Strong CYP3A inhibitors, including ketoconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
• Strong CYP3A inducers, including rifampin and moderate CYP3A inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use; if concurrent use with moderate CYP3A inducer unavoidable, ↓ glasdegib dosage.

• Tablets: 25 mg; 100 mg;

• PO (Adults): 100 mg once daily on Day 1–28 of each 28–day cycle. Continue treatment for 6 cycles (in absence of unacceptable toxicity). Concurrent use of CYP3A inducer — If current dosage 100 mg once daily, ↑ to 200 mg once daily; if current dosage 50 mg once daily, ↑ to 100 mg once daily.

Daurismo

• Binds to and inhibits Smoothened, one of the transmembrane proteins involved in hedgehog signal transduction.

• Improved survival.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: hedgehog pathway inhibitors

Absorption: 77% absorbed following oral administration; reduced by high-fat, high calorie foods.

Distribution: Extensively distributed to tissues.

Protein Binding: 91%.

Metabolism/Excretion: Mostly metabolized in the liver by the CYP3A4 isoenzyme, and to some extent by CYP2C8 and UGT1A9. 42% excreted in urine (20% as unchanged drug), 42% excreted in feces (20% as unchanged drug).

Half-life: 17.4 hr.

(plasma concentrations)

• Instruct patient to take glasdegib as directed. If vomiting occurs after dose, omit and take next scheduled dose next day. Take missed doses as soon as remembered and at least 12 hr before next scheduled dose; do not take 2 doses within 12 hr. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Advise patient to contact their health care professional immediately if signs and symptoms of QT prolongation (feeling faint, lightheaded, dizzy, or feel heart beating irregularly or fast) occur.
• Advise patient not to donate blood or blood products while taking glasdegib 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.
• Advise males not to donate semen during glasdegib therapy and for at least 30 days after the last dose.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products without consulting health care professional.
• Rep: May be teratogenic. Advise female of reproductive potential to use effective contraception and to avoid breastfeeding during and for at least 30 days after last dose. Advise males with a female partner of reproductive potential to use effective contraception, including a condom, even after vasectomy, during and for at least 30 days after last dose. May impair male fertility.

glas-DEG-ib

NDC Code^*

• 0069- Pfizer Laboratories Div Pfizer Inc
  • 0069-0298- Daurismo
    • 0069-0298-60- 60 TABLET, FILM COATED in 1 BOTTLE (0069-0298-60)

• 0069- Pfizer Laboratories Div Pfizer Inc
  • 0069-1531- Daurismo
    • 0069-1531-30- 30 TABLET, FILM COATED in 1 BOTTLE (0069-1531-30)