Glasdegib

Glasdegib is a prescription medication used for the treatment of acute myeloid leukemia (AML).

• Glasdegib is available under the following different brand names: Daurismo.

Common side effects of Glasdegib include:

• Anemia,
• Fatigue,
• Bleeding,
• Febrile neutropenia,
• Musculoskeletal pain,
• Nausea,
• Fluid retention/swelling,
• Low blood platelets (thrombocytopenia),
• Shortness of breath,
• Decreased appetite,
• Changes in taste,
• Inflammation and ulcers of mucus membranes,
• Constipation,
• Rash,
• Fever,
• Chest pain,
• Muscle spasms,
• Abdominal pain,
• Diarrhea,
• Vomiting,
• Cough,
• Dizziness,
• Headache,
• Pneumonia,
• Low blood sodium (hyponatremia),
• Weight loss,
• Decreased white blood cell count,
• Irregular heart rate, and
• Kidney problems.

Serious side effects of Glasdegib include:

• Black, tarry stools.
• Blood in the urine or stools.
• Chest pain.
• Coughing up blood.
• Decreased frequency or amount of urine.
• Difficult or labored breathing.
• Difficulty in swallowing.
• Dizziness or fainting.

Rare side effects of Glasdegib include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 25 mg
• 100 mg

Acute Myeloid Leukemia

Adult dosage

• 100 mg orally once a day on days 1-28 of each 28-day cycle; administer in combination with cytarabine 20 mg subcutaneously two times a day on days 1-10
• For patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Glasdegib has severe interactions with the following drug:
  • lefamulin
• Glasdegib has serious interactions with at least 174 other drugs.
• Glasdegib has moderate interactions with at least 21 other drugs.
• Glasdegib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Glasdegib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Glasdegib?”

Cautions

• Based on the mechanism of action and findings from animal studies, can cause embryo-fetal death or severe birth defects when administered to pregnant women (see Black Box Warnings and Pregnancy)
• Development of QTc prolongation and ventricular arrhythmias reported, including ventricular fibrillation and ventricular tachycardia; more frequent ECG monitoring is advised in patients with congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval (see Drug Interactions)
• Musculoskeletal adverse reactions
  • Musculoskeletal adverse reactions, which may be accompanied by CPK elevations, have occurred with this medication, which inhibits the hedgehog (Hh) pathway; the most frequent manifestations of musculoskeletal adverse reactions reported include musculoskeletal pain and muscle spasms; increased CPK laboratory values occurred in 16% of patients.
  • Obtain baseline CPK levels before initiating therapy and as clinically indicated (.g, if muscle symptoms are reported); obtain CPK and serum creatinine levels at least weekly in patients with musculoskeletal adverse reactions with concurrent CPK elevation greater than 2.5 times ULN until resolution of clinical signs and symptoms; depending on the severity of symptoms, temporary dose interruption, dose reduction, or discontinuation of therapy may be required for musculoskeletal adverse reactions or serum CPK elevation
• Drug interaction overview
  • Glasdegib is primarily metabolized by CYP3A.
  • Strong CYP3A inhibitors
    • Coadministration may increase glasdegib plasma concentrations and increase the risk for QT prolongation.
  • Strong or moderate CYP3A inducers
    • Avoid; coadministration may decrease glasdegib plasma concentrations, thereby reducing the efficacy.
    • May increase glasdegib dose if coadministration with moderate CYP3A4 inducers cannot be avoided.
• Prolonged QTc
  • Associated with concentration-dependent QTc prolongation.
  • Avoid coadministration with QTc prolonging drugs.
  • If unavoidable, monitor for increased risk of QTc interval prolongation.

Pregnancy and Lactation

• Based on its mechanism of action and findings in animal embryo-fetal developmental toxicity studies, glasdegib can cause fetal harm when administered to pregnant women
• Infertility
• Males: Based on findings in repeat-dose animal toxicity studies in rats, may impair fertility in males of reproductive potential; some effects on male reproductive organs did not recover
• Contraception
  • Females of reproductive potential
  • Use effective contraception during treatment and for at least 30 days after the last dose.
  • Do not donate blood during treatment and for at least 30 days after the last dose.
• Males
  • Unknown if present in semen
  • Advise males of the potential risk of exposure through semen and to use effective contraception, including a condom, even after a vasectomy, to avoid drug exposure to a pregnant partner or a female partner of reproductive potential during treatment for at least 30 days after the last dose.
  • Advise males to not donate sperm or blood during treatment and for at least 30 days after the last dose.
• Lactation
  • No data are available on the presence of human milk, its effects on the breastfed child, or its effect on milk production.
  • Advise women not to breastfeed or provide breast milk to infants or children during treatment and for at least 30 days after the last dose.