(glasdegib)

Prescribing Information
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8 USE IN SPECIFIC POPULATIONS

8 USE IN SPECIFIC POPULATIONS

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. 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.

Data

Animal Data

In embryo-fetal developmental toxicity studies, glasdegib was orally administered to pregnant rats and rabbits at doses up to 100 mg/kg/day during the period of organogenesis. Glasdegib resulted in embryo-fetal lethality (e.g., increased postimplantation loss and decreased numbers of live fetuses) in rats and rabbits at 50 mg/kg/day and 5 mg/kg/day, respectively, at maternal exposures approximately 4-times and 3-times the human exposure at the recommended dose [based on Cmax (rat) and AUC (rabbit)]. Doses of ≥10 mg/kg in rat [approximately 0.6-times the human exposure (Cmax) at the recommended dose] and ≥5 mg/kg in rabbit resulted in fetal developmental abnormalities and malformations consisting of craniofacial malformations, malformed limbs, paws/digits, trunk and tail, dilation of brain, malpositioned/malformed eyes, misshapen head, small tongue, absent palate, teeth and viscera, diaphragmatic hernia, edema, heart defects, rib and vertebral abnormalities, malformed or absent structures in the appendicular skeleton.

8.2 Lactation

Risk Summary

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.

8.3 Females and Males of Reproductive Potential

DAURISMO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

Pregnancy Testing

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 [see Nonclinical Toxicology (13.1)].

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 [see Nonclinical Toxicology (13.1)]. Men should seek advice on effective fertility preservation before treatment.

8.4 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.

8.5 Geriatric 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.

8.6 Renal 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 [see Clinical Pharmacology (12.3)].

Medication Guide

MEDICATION GUIDE

MEDICATION GUIDE
DAURISMO™ (DOOR-is-moe)
(glasdegib) tablets

What is the most important information I should know about DAURISMO?
DAURISMO can cause your baby to die before it is born (be stillborn) or cause your baby to have severe birth defects.
For females who can become pregnant:

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You should talk to your healthcare provider about the risks of DAURISMO to your unborn child.
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Your healthcare provider will do a pregnancy test within 7 days before you start taking DAURISMO.
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You should not use DAURISMO during pregnancy.
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You should use effective birth control during treatment and for at least 30 days after your last dose of DAURISMO. Talk with your healthcare provider about what birth control method is right for you during this time.
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Talk to your healthcare provider right away if you have unprotected sex or if you think that your birth control has failed.
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Tell your healthcare provider right away if you become pregnant or think that you may be pregnant.

For males:

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It is not known if DAURISMO is present in semen. Do not donate semen during treatment with DAURISMO and for at least 30 days after your last dose.
•
You should always use effective birth control, including a condom, even if you have had a vasectomy, during sex with female partners who are pregnant or who are able to become pregnant, during treatment with DAURISMO and for at least 30 days after your last dose to protect your female partner from being exposed to DAURISMO.
•
Tell your healthcare provider right away if your partner becomes pregnant or thinks she is pregnant while you are taking DAURISMO.

Exposure to DAURISMO during pregnancy:
If you think that you or your female partner may have been exposed to DAURISMO during pregnancy, talk to your healthcare provider right away. If you become pregnant during treatment with DAURISMO, you or your healthcare provider should report your pregnancy to Pfizer at 1-800-438-1985.

What is DAURISMO?
DAURISMO is a prescription medicine that is used with the medicine cytarabine to treat newly-diagnosed acute myeloid leukemia (AML) in adults who:

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are 75 years of age or older, or
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have other medical conditions that prevent the use of standard chemotherapy.

It is not known if DAURISMO is safe and effective in children.

Before you take DAURISMO, tell your healthcare provider about all of your medical conditions, including if you:

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have heart problems, including a condition called long QT syndrome.
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abnormal blood salt (electrolytes) levels.
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have muscle pain or spasms.
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have kidney problems.
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are pregnant or plan to become pregnant. See "What is the most important information I should know about DAURISMO?"
•
are breastfeeding or plan to breastfeed. It is not known if DAURISMO passes into your breast milk. Do not breastfeed or provide breast milk to infants or children during treatment with DAURISMO and for at least 30 days after the last dose. Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

How should I take DAURISMO?

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Take DAURISMO with the medicine cytarabine exactly as your healthcare provider tells you.
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Take DAURISMO 1 time each day, at about the same time each day.
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Take DAURISMO with or without food.
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Do not chew, split or crush DAURISMO tablets.
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If you miss a dose of DAURISMO, take it as soon as you remember. If it is less than 12 hours before your next dose, just skip the missed dose and take your next dose at your regular time. Do not take 2 doses of DAURISMO within 12 hours.
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If you vomit after taking a dose of DAURISMO, do not take an extra dose, just take your next dose at your regular time.
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Your healthcare provider will perform certain tests to check you for side effects before and during treatment with DAURISMO.
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Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with DAURISMO if you have certain side effects. Do not change your dose or stop taking DAURISMO unless your healthcare provider tells you.
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If you take too much DAURISMO, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking DAURISMO?

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Do not donate blood or blood products during treatment with DAURISMO and for at least 30 days after the last dose.
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Do not donate semen during treatment with DAURISMO and for at least 30 days after the last dose.

What are the possible side effects of DAURISMO?
DAURISMO can cause serious side effects, including:

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See "What is the most important information I should know about DAURISMO?"
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Changes in the electrical activity of your heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. Tell your healthcare provider right away if you feel faint, lightheaded, dizzy, or feel your heart beating irregularly or fast during treatment with DAURISMO.
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Muscle Problems. Muscle problems are common with DAURISMO, but can also sometimes be serious. DAURISMO can increase your risk of muscle pain or muscle spasms. Tell your healthcare provider right away if you develop any new or worsening muscle spasms, pain, tenderness or weakness during and after treatment with DAURISMO. Your healthcare provider should do a blood test to check for muscle problems and to check your kidney function before you start taking DAURISMO, during treatment, and if you develop muscle problems.

The most common side effects of DAURISMO with cytarabine include:

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low red blood cell count (anemia)
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tiredness
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bleeding
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fever with low white blood cell count
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muscle pain
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swelling of arms or legs
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low platelet count
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nausea
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shortness of breath
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decreased appetite
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changes in taste
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pain or sores in your mouth or throat
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constipation
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rash

DAURISMO may affect fertility in males. Talk to your healthcare provider if this is a concern for you.
These are not all of the possible side effects of DAURISMO.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store DAURISMO?

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Store DAURISMO at room temperature between 68°F to 77°F (20°C to 25°C).

Keep DAURISMO and all medicines out of the reach of children.

General information about the safe and effective use of DAURISMO.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use DAURISMO for a condition for which it was not prescribed. Do not give DAURISMO to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for more information about DAURISMO that is written for health professionals.

What are the ingredients in DAURISMO?
Active ingredient: glasdegib
Inactive ingredients: microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and magnesium stearate.
Film-coating:
25 mg tablets: Opadry II Yellow (33G120011) containing hypromellose, titanium dioxide, lactose monohydrate, macrogol, triacetin, and iron oxide yellow.
100 mg tablets: Opadry II Beige (33G170003) containing hypromellose, titanium dioxide, lactose monohydrate, macrogol, triacetin, iron oxide yellow, and iron oxide red.

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LAB-1285-4.0
For more information, go to www.DAURISMO.com or call 1-800-438-1985.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 12/2024

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