Glasdegib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Bhavya Bellannagari[2]
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Black Box Warning
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WARNING: EMBRYO-FETAL TOXICITY
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)
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Overview
Glasdegib is a Acetylcholine release inhibitor, Adrenergic receptor agonist that is FDA approved for the (type of indication of drug) of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
ULTOMIRIS is indicated for:
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.
Dosage Forms And Strengths
- DAURISMO 100 mg tablets: round, pale orange film-coated tablet debossed with "Pfizer" on one side and "GLS 100" on the other.
- DAURISMO 25 mg tablets: round, yellow film-coated tablet debossed with "Pfizer" on one side and "GLS 25" on the other.
Recommended Dosage and Schedule
- 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.
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 serum creatine kinase 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. Repeat ECG if abnormal.
- Certain patients may require more frequent and ongoing ECG monitoring.
- Manage any abnormalities promptly
Dosage Modification for Concomitant Use with Moderate CYP3A4 Inducers
- Avoid concomitant use of DAURISMO with moderate CYP3A4 inducers. If concomitant use of moderate CYP3A4 inducers cannot be avoided, increase the DAURISMO dosage as tolerated as shown in Table 2. After the moderate CYP3A4 inducer has been discontinued for 7 days, resume the DAURISMO dose taken prior to initiating the moderate CYP3A4 inducer.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding DAURISMO Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
Non–Guideline-Supported Use
There is limited information regarding DAURISMO Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding DAURISMO FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding DAURISMO Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
Non–Guideline-Supported Use
There is limited information regarding DAURISMO Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
Contraindications
None
Warnings
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WARNING: EMBRYO-FETAL TOXICITY
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)
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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. 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. Advise females of reproductive potential to use effective contraception during treatment with DAURISMO and for at least 30 days after the last dose. Advise women not to breastfeed during treatment with DAURISMO and for at least 30 days after the last dose.
Males
Advise male patients with female partners of the potential risk of exposure through semen and to use effective contraception, including a condom, even after vasectomy, to avoid drug exposure to a pregnant partner or a female partner of reproductive potential during treatment with DAURISMO and for at least 30 days after the last dose.
Blood Donation
Advise patients not to donate blood or blood products while taking DAURISMO and for at least 30 days after the last dose of DAURISMO 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 increases to greater than 500 ms. Discontinue DAURISMO permanently for patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
Adverse Reactions
Clinical Trials Experience
Central Nervous System
- (list/description of adverse reactions)
Cardiovascular
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Respiratory
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Gastrointestinal
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Hypersensitive Reactions
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Miscellaneous
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Condition 2
Central Nervous System
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Cardiovascular
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Respiratory
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Gastrointestinal
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Hypersensitive Reactions
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Miscellaneous
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Postmarketing Experience
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Drug Interactions
table
Use in Specific Populations
Pregnancy
- 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. 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.
- 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. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Glasdegib in women who are pregnant.
Labor and Delivery
The safety and effectiveness of DAURISMO during labor and delivery have not been evaluated.
Nursing Mothers
There are no data on the presence of glasdegib or its active metabolites in human milk, the effects of the drug on the breastfed child, or its effect on milk production. Because of the potential for serious adverse reactions in a breastfed child from DAURISMO, advise women who are taking DAURISMO not to breastfeed or provide breast milk to infants or children during treatment with DAURISMO and for at least 30 days after the last dose.
Pediatric Use
The safety and effectiveness of DAURISMO have not been established in pediatric patients. In repeat-dose toxicity studies in rats, oral administration of DAURISMO resulted in adverse changes in growing bone, teeth, and testis. Effects on bone consisted of partial to complete closure of the epiphyseal plate. Effects in growing incisor teeth included degeneration/necrosis of ameloblasts, and complete tooth loss with oral ulceration. Reproductive tissue toxicity was evidenced by testicular degeneration and hypospermatogenesis. These effects in bone, teeth and testis were observed after administration of DAURISMO for 26 weeks at greater than or equal to 50 mg/kg/day corresponding to approximately 6.6-times the steady state AUC in patients at the recommended human dose.
Geriatic Use
Of the total number of subjects in clinical studies of DAURISMO with low-dose cytarabine (N=88), 98% of the patients were age 65 years or older and 60% of the patients were age 75 years or older. There were insufficient patients younger than age 65 years to determine differences in adverse reactions reported from patients older than 65.
Gender
There is no FDA guidance on the use of DAURISMO with respect to specific gender populations.
Race
There is no FDA guidance on the use of DAURISMO with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of DAURISMO in patients with renal impairment.
Hepatic Impairment
No dosage modification is recommended for patients with mild to severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 89 mL/min). 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.
Females of Reproductive Potential and Males
Conduct pregnancy testing in females of reproductive potential within 7 days prior to initiating therapy with DAURISMO.
Contraception
Females: Advise females of reproductive potential to use effective contraception during treatment with DAURISMO and at least 30 days after the last dose. Males: It is not known if glasdegib is 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 with DAURISMO and for at least 30 days after the last dose. Advise males to not donate semen during treatment with DAURISMO for at least 30 days after the last dose
Infertility
Males: Based on findings in repeat-dose animal toxicity studies in rats, DAURISMO may impair fertility in males of reproductive potential. Some effects on male reproductive organs did not recover. Men should seek advice on effective fertility preservation before treatment.
Immunocompromised Patients
There is no FDA guidance one the use of DAURISMO in patients who are immunocompromised.
Others
(Description)
Administration and Monitoring
Administration
(Oral/Intravenous/etc)
Monitoring
Condition 1
(Description regarding monitoring, from Warnings section)
Condition 2
(Description regarding monitoring, from Warnings section)
Condition 3
(Description regarding monitoring, from Warnings section)
IV Compatibility
There is limited information regarding the compatibility of Glasdegib and IV administrations.
Overdosage
Acute Overdose
Signs and Symptoms
(Description)
Management
(Description)
Chronic Overdose
Signs and Symptoms
(Description)
Management
(Description)
Pharmacology
Glasdegib
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Mechanism of Action
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Nonclinical Toxicology
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Clinical Studies
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How Supplied
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Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
(Patient Counseling Information)
Precautions with Alcohol
Alcohol-Glasdegib interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Glasdegib Brand Names in the drug label.
Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
Drug Shortage Status
Drug Shortage
Price
References
The contents of this FDA label are provided by the National Library of Medicine.