Glasdegib

Glasdegib is an inhibitor of the Hedgehog pathway. Glasdegib binds to and inhibits Smoothened, a transmembrane protein involved in hedgehog signal transduction.

• DAURISMO is 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. 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.ICD-10: C95.90

• None. None.contraindicated

Recommended dosage: 100 mg orally once daily. ( 2.1 ) 2.1 Recommended Dosage and Schedule The recommended dosage of DAURISMO is 100 mg orally once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control. For patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response. Administer DAURISMO with or without food. Do not split or crush DAURISMO tablets. Administer DAURISMO about the same time each day. If a dose of DAURISMO is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of DAURISMO is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses of DAURISMO within 12 hours. 2.2 Monitoring and Dosage Modifications Assess complete blood counts, electrolytes, renal, and hepatic function prior to the initiation of DAURISMO and at least once weekly for the first month. Monitor electrolytes and renal function once monthly for the duration of therapy. Obtain creatine phosphokinase (CPK) levels prior to initiating DAURISMO and as indicated clinically thereafter (e.g., if muscle symptoms are reported). Monitor electrocardiograms (ECGs) prior to the initiation of DAURISMO, approximately one week after initiation, and then once monthly for the next two months to assess for QTc prolongation.

• Blood Donation: Advise patients not to donate blood or blood products during treatment with DAURISMO and for at least 30 days after the last dose. ( 5.1 ) • QTc Interval Prolongation: Monitor electrocardiograms and electrolytes. If QTc prolongation occurs, interrupt treatment with DAURISMO. ( 2.2 , 5.2 ) • Musculoskeletal Adverse Reactions: Obtain creatine phosphokinase (CPK) and serum creatinine levels prior to initiating DAURISMO and as indicated clinically thereafter. Temporary dose interruption, dose reduction, or discontinuation of DAURISMO may be required for musculoskeletal adverse reactions or serum CPK elevation. ( 2.2 , 5.3 ) 5.1 Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal embryo-fetal developmental toxicity studies, DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. There are no clinical data on the use of DAURISMO in pregnant women. In animal embryo-fetal developmental toxicity studies, glasdegib caused embryotoxicity, fetotoxicity and teratogenicity at maternal exposures that were less than the human exposure at the recommended human dose of 100 mg [see Use in Specific Populations (8.1 , 8.2) , Clinical Pharmacology (12.1) ] . Advise pregnant women of the potential risk to the fetus. Females of Reproductive Potential DAURISMO is not recommended for use during pregnancy. Conduct pregnancy testing in female patients of reproductive potential prior to initiating DAURISMO treatment.

The following clinically-significant adverse reactions are described elsewhere in the labeling: • QTc Interval Prolongation [see Warnings and Precautions (5.2) ] • Musculoskeletal Adverse Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥20%) are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety profile of DAURISMO is based on experience in the BRIGHT AML 1003 study for 111 adults with newly-diagnosed AML and 14 adults with other conditions for which DAURISMO is not indicated [see Clinical Studies (14) ] . Patients were treated with DAURISMO 100 mg daily in combination with low-dose cytarabine (N=84) or low-dose cytarabine alone (N=41). The median duration of treatment in the DAURISMO with low-dose cytarabine arm was 83 days (range 3 to 972 days), and the median duration of treatment in the low-dose cytarabine alone arm was 47 days (range 6 to 239 days). The median exposure to DAURISMO in the DAURISMO with low-dose cytarabine arm was 76 days (range 3 to 954 days).

Lactation: Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action and findings in animal embryo-fetal developmental toxicity studies, DAURISMO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no clinical data on the use of DAURISMO in pregnant women to inform of a drug-associated risk of major birth defects and miscarriage. DAURISMO is not recommended for use during pregnancy. Conduct pregnancy testing in female patients of reproductive potential prior to initiating treatment with DAURISMO. Report pregnancy exposures to Pfizer at 1-800-438-1985. In animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of DAURISMO during organogenesis at maternal exposures that were less than the human exposure at the recommended dose resulted in embryotoxicity, fetotoxicity and teratogenicity in rats and rabbits (see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S.

Metabolism

DAURISMO at 5 mg to 600 mg once daily (0.05 to 6 times the recommended dose) result in a dose proportional increase in glasdegib peak concentrations (C max ) and area under the curve over the dosing interval (AUC 0-Tau ). Steady-state plasma levels are reached by 8 days of daily dosing.

There is no specific antidote for DAURISMO. Management of DAURISMO overdose should include symptomatic treatment and ECG monitoring. Glasdegib has been administered in clinical studies up to a dose of 640 mg/day. At the highest dosage, the adverse reactions that were dose limiting were nausea, vomiting, dehydration, hypotension, fatigue, and dizziness.

• Nov 21, 2018NDANDA210656Pfizer

1. 1Death11024%
2. 2Febrile Neutropenia6815%
3. 3Pneumonia4810%
4. 4Off Label Use347.3%
5. 5Neoplasm Progression286.0%
6. 6Neutropenia224.7%
7. 7Sepsis153.2%
8. 8Toxicity To Various Agents132.8%
9. 9Electrocardiogram Qt Prolonged122.6%
10. 10Product Use In Unapproved Indication112.4%
11. 11Septic Shock112.4%
12. 12Decreased Appetite102.1%
13. 13Drug Ineffective102.1%
14. 14Infection102.1%
15. 15Pyrexia102.1%

The 10 most recently updated of 30 ClinicalTrials.gov registrations naming Glasdegib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia.
  Recruiting · Phase 3 · Interventional · 339 enrolled · Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
  NCT06713837updated 2026-06-10
• Molecular Profiling of Advanced Soft-tissue Sarcomas
  Completed · Phase 3 · Interventional · 603 enrolled · Institut National de la Santé Et de la Recherche Médicale, France
  NCT03784014updated 2026-04-29
• Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia
  Completed · Phase 2 · Interventional · 75 enrolled · University of Nebraska
  NCT03226418updated 2026-03-10
• CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia
  Active not recruiting · Phase 2 · Interventional · 30 enrolled · University of California, Irvine
  NCT04231851updated 2026-03-06
• A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies
  Completed · Phase 1 · Interventional · 48 enrolled · Pfizer
  NCT02038777updated 2025-02-26
• Glasdegib for Chronic Graft-Versus-Host Disease
  Terminated · Phase 1 · Phase 2 · Interventional · 15 enrolled · Fred Hutchinson Cancer Center
  NCT04111497updated 2024-10-29
• A Study Of PF-04449913 In Select Hematologic Malignancies
  Completed · Phase 1 · Interventional · 47 enrolled · Pfizer
  NCT00953758updated 2024-04-25
• Glasdegib (PF-04449913) With Temozolomide Newly Diagnosed Glioblastoma
  Completed · Phase 1 · Phase 2 · Interventional · 75 enrolled · Grupo Español de Investigación en Neurooncología
  NCT03466450updated 2024-03-28
• A Study Of PF-04449913 Administered Alone In Select Solid Tumors
  Completed · Phase 1 · Interventional · 23 enrolled · Pfizer
  NCT01286467updated 2024-03-06
• A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients
  Completed · Phase 1 · Interventional · 73 enrolled · Pfizer
  NCT02367456updated 2024-01-19

Frequently asked questions

How does Glasdegib work?

Glasdegib is an inhibitor of the Hedgehog pathway. Glasdegib binds to and inhibits Smoothened, a transmembrane protein involved in hedgehog signal transduction.

What is Glasdegib used for?

According to FDA labeling, Glasdegib carries indications including: DAURISMO is 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. 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Glasdegib?

Glasdegib is classified as Hedgehog pathway inhibitors, Hedgehog Pathway Inhibitor, Smoothened Receptor Antagonists, Cellular Proliferation Alteration.

What are the brand names for Glasdegib?

Glasdegib is marketed under brand names including Daurismo.

What are the contraindications for Glasdegib?

Glasdegib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.