Glasdegib film-coated tablets are a type of Smoothened (SMO) inhibitor. Approved in the United States in 2018, they are indicated for the treatment of newly diagnosed acute myeloid leukemia (AML) in combination with low-dose cytarabine. This therapeutic option is specifically intended for adult patients who are ≥ 75 years old or who cannot receive intensive induction chemotherapy due to comorbidities.
How to Use Glasdegib Film-Coated Tablets
Standard Dosing Regimen
Dose and Treatment Course: The recommended dose is 100 mg taken orally once daily, in combination with cytarabine (20 mg administered subcutaneously twice daily, on Days 1 to 10). One treatment cycle is 28 days. If there is no intolerable toxicity or disease progression, it is recommended to continue treatment for at least 6 cycles.
Administration Requirements: The tablets can be taken with or without food, and must be swallowed whole—they should not be split or crushed. Take the medication at the same fixed time every day. If vomiting occurs after administration or a dose is missed, do not make up for the missed dose; take the next dose as scheduled.
Precautions for Combined Medication
Avoid concurrent use with strong CYP3A4 inducers (e.g., rifampicin), as this may reduce the blood concentration of glasdegib.
Strong CYP3A4 inhibitors (e.g., ketoconazole) may increase the risk of QT interval prolongation, requiring close monitoring.
Dose Adjustment of Glasdegib Film-Coated Tablets
Dose Adjustment for QT Interval Prolongation
QTc interval > 480 ms to 500 ms: Correct electrolyte imbalances, discontinue concurrent use of drugs that prolong the QT interval, and monitor the electrocardiogram (ECG) weekly until the QT interval returns to normal.
QTc interval > 500 ms: Discontinue glasdegib temporarily. Once the QT interval recovers, resume treatment at a reduced dose of 50 mg per day. In case of life-threatening arrhythmias, discontinue the drug permanently.
Dose Adjustment for Hematological Toxicity
If platelets < 10 × 10⁹/L or neutrophils < 0.5 × 10⁹/L persist for more than 42 days: Discontinue glasdegib and cytarabine permanently.
Dose Adjustment for Non-Hematological Toxicity
Grade 3 toxicity: Discontinue the drug temporarily until symptoms resolve to Grade ≤ 1. After recovery, resume treatment at the original dose or a reduced dose of 50 mg per day.
Grade 4 toxicity: Discontinue the drug permanently.
Medication Use in Special Populations for Glasdegib Film-Coated Tablets
Patients with Hepatic or Renal Impairment
Hepatic Function: No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh Class A/B); use is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) due to insufficient data.
Renal Function: No dose adjustment is needed for patients with mild to moderate renal impairment (eGFR ≥ 30 mL/min); caution is advised in patients with severe renal impairment (eGFR 15–29 mL/min).
Pregnancy and Lactation
Pregnancy: Glasdegib has embryo-fetal toxicity, so it is contraindicated in pregnant women. Before starting treatment, confirm that the patient is not pregnant. Effective contraception (non-hormonal or barrier methods) must be used during treatment and for 30 days after the last dose.
Lactation: Breastfeeding is prohibited during treatment and for 30 days after discontinuing the drug.
Pediatric and Geriatric Patients
Pediatric Patients: The efficacy of glasdegib has not been established in pediatric patients, and it is contraindicated in those under 18 years of age. Animal studies have shown toxic effects on bone, tooth, and testicular development.
Geriatric Patients: In clinical studies, 98% of patients were ≥ 65 years old. No additional dose adjustment is required, but enhanced monitoring for adverse reactions is recommended.
Other Precautions
Male Patients: Male patients must use condoms during treatment and for 30 days after discontinuing the drug to avoid exposure through semen.
Impact on Fertility: Glasdegib may impair male fertility. It is recommended that male patients consult a healthcare provider about fertility preservation measures before starting treatment.
