label

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

DAURISMO safely and effectively. See full prescribing information for

DAURISMO.

DAURISMO

(glasdegib) tablets, for oral use

Initial U.S. Approval: 2018

WARNING: EMBRYO-FETAL TOXICITY

See full prescribing information for complete boxed warning.

 DAURISMO can cause embryo-fetal death or severe birth defects

when administered to a pregnant woman. DAURISMO is

embryotoxic, fetotoxic, and teratogenic in animals. (5.1, 8.1)

 Conduct pregnancy testing in females of reproductive potential

prior to initiation of 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. (5.1, 8.1, 8.3)

 Advise males of the potential risk of exposure through semen and to

use condoms with a pregnant partner or a female partner of

reproductive potential during treatment with DAURISMO and for

at least 30 days after the last dose to avoid potential drug exposure.

(5.1, 8.3)

--------------------------- INDICATIONS AND U SAGE ----------------------------

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. (1)

Limitation of Use: DAURISMO has not been studied in patients with the

comorbidities of severe renal impairment or moderate-to-severe hepatic

impairment.

----------------------- DOSAGE AND ADMINISTRATION -----------------------

Recommended dose: 100 mg orally, once daily. (2.1)

--------------------- DOSAGE FORMS AND STRENGTHS ---------------------

Tablets: 100 mg, 25 mg. (3)

------------------------------ CONTRAINDICATIONS ------------------------------

None. (4)

----------------------- WARNINGS AND PRECAUTIONS -----------------------

 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)

------------------------------ ADVERSE REACTIONS ------------------------------

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.

------------------------------DRUG INTERACTIONS-------------------------------

 Strong CYP3A4 Inhibitors: Consider alternative therapies that are not

strong CYP3A inhibitors or monitor for increased risk of adverse reactions,

including QTc interval prolongation. (7)

 Strong CYP3A4 Inducers: Avoid concomitant use with DAURISMO. (7)

 QTc Prolonging Drugs: Avoid co-administration with DAURISMO. If

co-administration is unavoidable, monitor for increased risk of QTc

interval prolongation. (7)

----------------------- USE IN SPECIFIC POPULATIONS -----------------------

 Lactation: Advise women not to breastfeed. (8.2)

See 17 for PATIENT COUNSELING INFORMATION and Medication

Guide.

Revised: 11/2018

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: EMBRYO-FETAL TOXICITY

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose and Schedule

2.2 Monitoring and Dose Modifications

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Embryo-Fetal Toxicity

5.2 QT

Interval Prolongation

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

* Sections or subsections omitted from the full prescribing information are

not listed.

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

FULL PRESCRIBING INFORMATION

WARNING: EMBRYO-FETAL TOXICITY

DAURISMO can cause embryo-fetal death or severe birth defects when administered to a

pregnant woman. DAURISMO is embryotoxic, fetotoxic, and teratogenic in animals [see

Warnings and Precautions (5.1), Use in Specific Populations (8.1)].

Conduct pregnancy testing in females of reproductive potential prior to initiation of

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

[see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)].

Advise males of the potential risk of DAURISMO exposure through semen and to use

condoms with a pregnant partner or a female partner of reproductive potential during

treatment with DAURISMO and for at least 30 days after the last dose to avoid potential

drug exposure [see Warnings and Precautions (5.1), Use in Specific Populations (8.3)].

1 INDICATIONS AND USAGE

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.

Limitation of Use: DAURISMO has not been studied in patients with the comorbidities of severe renal

impairment or moderate-to-severe hepatic impairment.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose and Schedule

The recommended dose 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 Dose 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

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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 [see Warnings and Precautions (5.2)]. Manage any abnormalities promptly [see

Adverse Reactions (6.1)].

See Table 1 for dose modification guidelines for patients who develop an adverse reaction.

Table 1. Recommended Dose Modifications for Adverse Reactions

Adverse Reaction Recommended Action

QTc interval

prolongation on at

least 2 separate

electrocardiograms

(ECGs)

QTc interval greater

than 480 ms to

500 ms

Assess electrolyte levels and supplement as clinically indicated.

Review and adjust concomitant medications with known QTc

interval-prolonging effects [see Drug Interactions (7)].

Monitor ECGs at least weekly for 2 weeks following resolution of

QTc prolongation to less than or equal to 480 ms.

QTc interval greater Assess electrolyte levels and supplement as clinically indicated.

than 500 ms

Review and adjust concomitant medications with known QTc

interval-prolonging effects [see Drug Interactions (7)].

Interrupt DAURISMO.

Resume DAURISMO at a reduced dose of 50 mg once daily

when QTc interval returns to within 30 ms of baseline or less than

or equal to 480 ms.

Monitor ECGs at least weekly for 2 weeks following resolution of

QTc prolongation.

Consider re-escalating the dose of DAURISMO to 100 mg daily

if an alternative etiology for the QTc prolongation can be

identified.

QTc interval

prolongation with

life-threatening

arrhythmia

Discontinue DAURISMO permanently.

Hematologic

toxicity

Platelets less than

10 Gi/L for more

than 42 da

s in the

Discontinue DAURISMO and low-dose cytarabine permanently.

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Table 1. Recommended Dose Modifications for Adverse Reactions

Adverse Reaction Recommended Action

absence of disease

Neutrophil count

less than 0.5 Gi/L

for more than

42 days in the

absence of disease

Discontinue DAURISMO and low-dose cytarabine permanently.

Nonhematologic

toxicity

Grade 3

Interrupt DAURISMO and/or low-dose cytarabine until

symptoms reduce to mild or return to baseline.

Resume DAURISMO at the same dose level, or at a reduced dose

of 50 mg.

Resume low-dose cytarabine at the same dose level, or at a

reduced dose of 15 mg or 10 mg.

If toxicity recurs, discontinue DAURISMO and low-dose

cytarabine.

If toxicity is attributable to DAURISMO only, low-dose

cytarabine may be continued.

Grade 4

Discontinue DAURISMO and low-dose cytarabine permanently.

*Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.

3 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.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

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.

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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. 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 [see Use

in Specific Populations (8.2, 8.3)].

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 [see Use in Specific Populations (8.3)].

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.

5.2 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 [see Dosage and Administration (2.2)]. Concomitant use

of DAURISMO with drugs known to prolong the QTc interval and CYP3A4 inhibitors may increase the risk of

QTc interval prolongation [see Drug Interactions (7), Clinical Pharmacology (12.2)]. 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 [see

Dosage and Administration (2.2)].

6 ADVERSE REACTIONS

The following clinically significant adverse reaction is described elsewhere in the labeling:

 QT Interval Prolongation [see Warnings and Precautions (5.2)]

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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). Thirty-two patients (38%) were

treated with DAURISMO with low-dose cytarabine for at least 6 months and 14 patients (17%) were treated for

at least 1 year.

Serious adverse reactions were reported in 79% of patients treated in the DAURISMO with low-dose cytarabine

arm. The most common (≥5%) serious adverse reactions in patients receiving DAURISMO with low-dose

cytarabine were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%), and

sepsis (7%).

Dose reductions associated with adverse reactions were reported in 26% of patients treated with DAURISMO

with low-dose cytarabine, and the most common reasons (≥2%) for dose reductions due to adverse reactions

were muscle spasms (5%), fatigue (4%), febrile neutropenia (4%), anemia (2%), thrombocytopenia (2%), and

ECG QT prolonged (2%). Adverse reactions leading to permanent discontinuation were reported in 36% of

patients treated with DAURISMO with low-dose cytarabine, and the most common (≥2%) reasons for

permanent discontinuation were pneumonia (6%), febrile neutropenia (4%), sepsis (4%), sudden death (2%),

myocardial infarction (2%), nausea (2%), and renal insufficiency (2%).

Adverse reactions reported in the first 90 days of therapy on the BRIGHT AML 1003 study are shown in

Table 2.

Table 2. Adverse Reactions Occurring in ≥ 10% of Patients

a,b

Within the First 90 Days of Therapy in

BRIGHT AML 1003

Body System Adverse Reactions DAURISMO With

Low-Dose Cytarabine

N=84

Low-Dose Cytarabine

N=41

All Grades

Grade ≥ 3

All Grades

Grade ≥ 3

Blood and lymphatic Anemia 43 41 42 37

system disorder Hemorrhage

36 6 42 12

Febrile neutropenia 31 31 22 22

Thrombocytopenia 30 30 27 24

General disorders and

Fatigue

36 14 32 7

administration site Edema

30 0 20 2

conditions Mucositis

21 1 12 0

Pyrexia 18 1 22 2

Chest pain

12 1 2 0

Musculoskeletal and

connective tissue disorders

Musculoskeletal pain

Muscle spas

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Body System Adverse Reactions DAURISMO With

Low-Dose Cytarabine

N=84

Low-Dose Cytarabine

N=41

All Grades

Grade ≥ 3

All Grades

Grade ≥ 3

Gastrointestinal disorders Nausea 29 1 12 2

Constipation 20 1 12 0

Abdominal pain

19 0 12 0

Diarrhea

18 4 22 0

Vomiting 18 2 10 2

Respiratory thoracic and

mediastinal disorders

Dyspnea

Cough

Metabolism and nutrition

disorders

Decrease appetite 21 1 7 2

Nervous system disorders Dysgeusia

Dizziness

Headache

Skin and subcutaneous

tissue disorders

Rash

20 2 7 2

Infection and infestations

Pneumonia

19 15 24 22

Investigations Hyponatremia 11 6 0 0

Platelet count decreased 15 15 10 10

Weight decreased 13 0 2 0

White blood cell count

decreased

11 11 5 2

Cardiac disorders Atrial arrhythmia

13 4 7 2

Renal and urinary

disorders

Renal insufficiency

19 5 10 0

Abbreviations: N = number of patients.

Preferred terms were retrieved by applying the Medical Dictionary for Regulatory Activities (MedDRA) version 19.1.

BRIGHT AML 1003 used National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Adverse reactions include events that commenced within 28 days after the last treatment dose.

Adverse reactions with ≥10% incidence in the DAURISMO with low-dose cytarabine arm or the low-dose cytarabine arm are included.

No Grade 5 events in the DAURISMO with low-dose cytarabine or low-dose cytarabine alone arm.

Hemorrhage includes petechiae, epistaxis, hematoma, contusion, rectal hemorrhage, anal hemorrhage, ecchymosis, gingival bleeding, hematuria,

mouth hemorrhage, purpura, cerebral hemorrhage, eye contusion, eye hemorrhage, gastric hemorrhage, gastrointestinal hemorrhage, hematemesis,

hemoptysis, hemorrhage, implant site hematoma, injection site bruising, retroperitoneal hematoma, thrombotic thrombocytopenic purpura, tracheal

hemorrhage, conjunctival hemorrhage, disseminated intravascular coagulation, eyelid hematoma, hematochezia, hemorrhage intracranial,

hemorrhoidal hemorrhage, lower gastrointestinal hemorrhage, retinal hemorrhage, and subdural hematoma.

Fatigue includes asthenia and fatigue.

Edema includes edema peripheral, edema, fluid overload, fluid retention, and swelling face.

Mucositis includes mucosal inflammation, oropharyngeal pain, stomatitis, anal ulcer, gingival pain, laryngeal inflammation, esophagitis, oral pain,

aphthous ulcer, mouth ulceration, and pharyngeal inflammation.

Chest pain includes chest pain and non-cardiac chest pain.

Musculoskeletal pain includes pain in extremity, arthralgia, back pain, myalgia, musculoskeletal pain, musculoskeletal chest pain, neck pain, and

bone pain.

Muscle spasms includes muscle spasms and muscle tightness.

Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower.

Diarrhea includes diarrhea, colitis, and gastroenteritis.

Dyspnea includes dyspnea, hypoxia, bronchospasm, and respiratory failure.

Cough includes cough and productive cough.

Dysgeusia includes dysgeusia and ageusia.

Rash includes rash, pruritus, erythema, skin ulcer, rash maculo-papular, and rash pruritic.

Pneumonia includes pneumonia, pneumonia aspiration, and lung infection.

Atrial arrhythmia includes atrial fibrillation, bradycardia, tachycardia, and sinus tachycardia.

Renal insufficiency includes acute kidney injury, blood creatinine increased, oliguria, and renal failure.

The adverse reactions muscle spasms (4 in 12 patients) and decreased appetite (2 in 10 patients) worsened (i.e.

progressed from Grades ≤ 2 to Grade 3 or higher) after the first 90 days of therapy in BRIGHT AML 1003.

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Additional clinically-significant adverse reactions occurring in < 10% of patients treated with DAURISMO and

low-dose cytarabine in BRIGHT AML 1003 include:

 Dental disorders: loose tooth and toothache

 Skin and subcutaneous tissue disorders: alopecia

 Cardiac disorders: QT interval prolonged

Changes in selected post-baseline laboratory values that were observed in patients with newly-diagnosed AML

and other conditions for which DAURISMO is not indicated in the clinical trial are shown in Table 3.

Table 3. Selected Laboratory Abnormalities (≥ 15% )

Within the First 90 Days of Therapy in BRIGHT

AML 1003

Laboratory Abnormality

DAURISMO with Low-Dose

Cytarabine

Low-Dose Cytarabine

All Grades

Grade 3 or 4

All Grades

Grade 3 or 4

Creatinine increased 81 96 1 40 80 5

Hyponatremia 81 54 7 39 41 8

Hypomagnesemia 81 33 0 39 23 0

AST increased 80 28 1 40 23 0

Blood bilirubin increased 80 25 4 39 33 3

ALT increased 80 24 0 40 28 3

Alkaline phosphatase

increase

80 23 0 40 28 3

Hyperkalemia 81 16 1 40 8 3

CPK increased 38 16 0 17 6 0

Hypokalemia 81 15 0 40 23 0

Abbreviations: N = number of patients; AST = aspartate aminotransferase; ALT = alanine aminotransferase; CPK = creatinine

phosphokinase.

BRIGHT AML 1003 used National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.

Maximum severity based on the number of patients with available on-study laboratory data.

The following laboratory abnormalities worsened (i.e. progressed from Grades ≤ 2 to Grade 3 or higher) after

the first 90 days of therapy in BRIGHT AML 1003:

 hypophosphatemia (8 in 38 patients), creatinine increased (2 in 39 patients), and ALT increased (2 in

40 patients).

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7 DRUG INTERACTIONS

Table 4. Drug Interactions with DAURISMO

Strong CYP3A Inhibitors

Clinical Impact

 Co-administration of DAURISMO with strong CYP3A inhibitors

increased glasdegib plasma concentrations [see Clinical

Pharmacology (12.3)].

 Increased glasdegib concentrations may increase the risk of adverse

reactions including QTc interval prolongation [see Warnings and

Precautions (5.2)].

Prevention or

Management

 Consider alternative therapies that are not strong CYP3A4 inhibitors

during treatment with DAURISMO.

 Monitor patients for increased risk of adverse reactions including

QTc interval prolongation [see Warnings and Precautions (5.2)].

Strong CYP3A Inducers

Clinical Impact

Co-administration of DAURISMO with strong CYP3A inducers

decreased glasdegib plasma concentrations [see Clinical Pharmacology

(12.3)].

Prevention or

Management

Avoid co-administration of DAURISMO with strong CYP3A4 inducers.

QTc Prolonging Drugs

Clinical Impact

Co-administration of DAURISMO with QTc prolonging drugs may

increase the risk of QTc interval prolongation [see Warnings and

Precautions (5.2)].

Prevention or

Management

 Avoid co-administration of QTc prolonging drugs with DAURISMO

or replace with alternative therapies.

 If co-administration of a QTc prolonging drug is unavoidable, monitor

patients for increased risk of QTc interval prolongation [see Warnings

and Precautions (5.2)].

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

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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 C

max

(rat) and AUC (rabbit)]. Doses of ≥ 10 mg/kg in rat [approximately

0.6-times the human exposure (C

max

) 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)].

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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.

10 OVERDOSAGE

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 events reported were nausea, vomiting, dehydration, fatigue and dizziness.

11 DESCRIPTION

DAURISMO (glasdegib) is a potent small molecule inhibitor of Smoothened (SMO) for oral use. It is

formulated with the maleate salt of glasdegib. The molecular formula for glasdegib maleate is C

. The

molecular weight for glasdegib maleate is 490.51 Daltons. The chemical name of glasdegib maleate is

1-((2R,4R)-2-(1H-benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea maleate. The

molecular structure is shown below:

Glasdegib maleate is a white to pale colored powder with pKa values of 1.7 and 6.1. The aqueous solubility of

glasdegib maleate is 1.7 mg/mL.

Reference ID: 4353045

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

DAURISMO (glasdegib) is supplied as a film-coated tablet for oral use containing either 100 mg glasdegib

(equivalent to 131.1 mg glasdegib maleate) or 25 mg of glasdegib (equivalent to 32.8 mg glasdegib maleate)

together with microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and

magnesium stearate as inactive ingredients in the tablet. The film-coating consists of Opadry II

Beige

(33G170003) and Opadry II

Yellow (33G120011) containing: hypromellose, titanium dioxide, lactose

monohydrate, macrogol, triacetin, iron oxide yellow, and iron oxide red.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Glasdegib is an inhibitor of the Hedgehog pathway. Glasdegib binds to and inhibits Smoothened, a

transmembrane protein involved in hedgehog signal transduction.

In a murine xenotransplant model of human AML, glasdegib in combination with low-dose cytarabine,

inhibited increases in tumor size and reduced the percentage of CD45+/CD33+ blasts in the marrow to a greater

extent than glasdegib or low-dose cytarabine alone.

12.2 Pharmacodynamics

Cardiac Electrophysiology

The effect of glasdegib administration on corrected QT interval (QTc) was evaluated in a randomized,

single-dose, double-blind, 4-way crossover, placebo- and open-label moxifloxacin-controlled study in

36 healthy subjects. At therapeutic plasma concentrations for the recommended dose, achieved with a single

dose of 150 mg DAURISMO, the largest placebo and baseline-adjusted QTc interval change was 8 ms (90% CI:

6, 10 ms). At a two-fold therapeutic plasma concentration, achieved with a single dose of 300 mg DAURISMO,

the QTc change was 13 ms (90% CI: 11, 16 ms). Glasdegib is associated with concentration-dependent QTc

prolongation.

12.3 Pharmacokinetics

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

tau

). Steady-state plasma levels are reached by 8 days of daily dosing. The median accumulation ratio of

glasdegib ranged from 1.2 to 2.5 following once-daily dosing.

At DAURISMO 100 mg once daily, the geometric mean (geometric coefficient of variation, % CV) of

glasdegib C

max

was 1252 ng/mL (44%) and AUC

tau

was 17210 ng*hr/mL (54%) in patients with cancer.

Absorption

The mean absolute bioavailability of DAURISMO is 77%. Following 100 mg once daily dosing, glasdegib

median time to peak concentrations (T

max

) at steady-state ranged from 1.3 hours to 1.8 hours.

Effect of Food: A high-fat, high-calorie meal (total 800-1000 calories: 500-600 fat calories, 250 carbohydrate

calories and 150 protein calories) reduced area under the curve over time to infinity (AUC

inf

) by 16% and C

max

by 31%.

Distribution

Glasdegib is 91% bound to human plasma proteins in vitro. The geometric mean (%CV) apparent volume of

distribution (V

/F) was 188 L (20%) in patients with hematologic malignancies.

Reference ID: 4353045

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Elimination

Glasdegib has a mean ( SD) half-life of 17.4 h (3.7) and geometric mean (%CV) apparent clearance of

6.45 L/h (25%) following 100 mg once daily dosing in patients with hematologic malignancies.

Metabolism

Glasdegib is primarily metabolized by the CYP3A4 pathway, with minor contributions by CYP2C8 and

UGT1A9. Glasdegib accounts for 69% of the total circulating drug related material in plasma.

Excretion

Following a single oral dose of 100 mg radiolabeled glasdegib, 49% (17% unchanged) of the administered dose

was eliminated in the urine and 42% (20% unchanged) of the administered dose was eliminated in the feces.

Specific Populations

Age (25 to 92 years), sex, race (White, Black, Asian), body weight (43.5 to 145.6 kg), mild hepatic impairment

(total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1-1.5 x ULN and any AST) or mild to moderate renal

impairment (creatinine clearance [CLcr] 30-89 mL/min) did not have clinically meaningful effects on the

pharmacokinetics of glasdegib. The effect of moderate (total bilirubin 1.5-3 x ULN and any AST) and severe

(total bilirubin > 3 x ULN and any AST) hepatic impairment or severe renal impairment (CLcr 15-29 mL/min)

on glasdegib pharmacokinetics is unknown.

Drug Interaction Studies

Clinical Studies

Effect of Strong CYP3A4 Inhibitors on Glasdegib:

Coadminstration of ketoconazole (a strong inhibitor of CYP3A4) with DAURISMO increased the glasdegib

AUC

inf

by 2.4-fold and C

max

by 1.4-fold over glasdegib given alone [see Drug Interactions (7)].

Effect of Strong CYP3A4 Inducers on Glasdegib:

Coadminstration of rifampin (a strong inducer of CYP3A4) with DAURISMO decreased glasdegib AUC

inf

70% and C

max

by 35% [see Drug Interactions (7)].

Effect of Gastric Acid Reducing Agents on Glasdegib:

Coadministration of rabeprazole (a proton pump inhibitor) with DAURISMO did not alter glasdegib AUC

inf

but

decreased C

max

by 20%.

In Vitro Studies

Effect of Glasdegib on Cytochrome P450 (CYP) Substrates:

Glasdegib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A, and does

not induce CYP1A2, CYP2B6, and CYP3A in vitro.

Effect of Transporters on Glasdegib:

Glasdegib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

Effect of Glasdegib on Transporters:

Glasdegib inhibits P-gp, BCRP, multidrug and toxin extrusion (MATE) protein 1, and MATE-2K, but not

organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, and

organic cation transporter (OCT)2 in vitro.

Reference ID: 4353045

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with glasdegib.

Glasdegib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in

the in vitro chromosome aberration assay in human lymphocytes. Glasdegib was not clastogenic or aneugenic in

the rat micronucleus assay.

Based on nonclinical safety findings, glasdegib has the potential to impair reproductive function in males. Men

should seek advice on effective fertility preservation before treatment. In repeat-dose toxicity studies in rats,

findings observed in the male reproductive tract included adverse testicular changes with glasdegib at doses

50 mg/kg/day, and consisted of minimal to severe hypospermatogenesis characterized by partial to complete

loss of spermatogonia, spermatocytes and spermatids and testicular degeneration. Hypospermatogenesis did not

recover whereas testicular degeneration did recover. The dose at which testicular effects were observed in male

rats was identified as 50 mg/kg/day with corresponding systemic exposures that were approximately 6.6-times

(based on AUC) those associated with the observed human exposure at the 100 mg once daily dose.

14 CLINICAL STUDIES

The efficacy of DAURISMO in combination with low-dose cytarabine was evaluated in a multicenter, open-

label, randomized study (Study BRIGHT AML 1003, NCT01546038) that included 115 patients age 55 years

or older with newly-diagnosed AML who met at least one of the following criteria: a) age > 75 years, b) severe

cardiac disease, c) baseline Eastern Cooperative Oncology Group (ECOG) performance status of 2, or

d) baseline serum creatinine >1.3 mg/dL. Patients were randomized 2:1 to receive DAURISMO at a 100 mg

daily dose with low-dose cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle

(N=77) or low-dose cytarabine alone (N=38) in 28-day cycles until disease progression or unacceptable

toxicity. Patients were stratified by cytogenetic risk (good/intermediate or poor).

The baseline demographic and disease characteristics are shown in Table 5. The two treatment arms were

generally balanced with respect to the baseline demographics and disease characteristics (see Table 5).

Reference ID: 4353045

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Table 5. Baseline Demographic and Disease Characteristics in Patients with AML

Demographic and Disease

Characteristics

DAURISMO With

Low-Dose Cytarabine

(N=77)

Low-Dose Cytarabine Alone

(N=38)

Demographics

Age

Median (Min, Max) (Years)

≥ 75

ears N (%)

77 (64, 92)

47 (61)

76 (58, 83)

23 (61)

Sex, N (%)

Male

Female

59 (77)

18 (23)

23 (61)

15 (39)

Race, N (%)

White

Black or African American

Asian

75 (97)

1 (1)

38 (100)

0 (0)

Disease History, N (%)

De Novo AML

Secondary AML

38 (49)

39 (51)

18 (47)

20 (53)

Prior Hypomethylating Agent Use 11 (14) 6 (16)

ECOG PS

, N (%)

0 to 1

35 (46)

41 (53)

20 (53)

18 (47)

Cytogenetic Risk Status, N (%)

Good/Intermediate

Poo

48 (62)

29 (38)

21 (55)

17 (45)

Baseline Severe Cardiac Disease 51 (66) 20 (53)

Baseline Serum Creatinine >1.3 mg/dL 15 (19) 5 (13)

Abbreviations: AML = acute myeloid leukemia; N = number of patients; ECOG PS = Eastern Cooperative Oncology Group Performance Status.

Baseline ECOG PS was not reported for one patient in the DAURISMO with low-dose cytarabine arm.

Efficacy was established on the basis of overall survival (OS) from the date of randomization to death from any

cause. With a median follow-up of approximately 20 months, the DAURISMO with low-dose cytarabine arm

was superior to low-dose cytarabine alone arm (Figure 1). The efficacy results are shown in Table 6.

Improvement in OS was consistent across prespecified cytogenetic risk subgroups.

Table 6. Efficacy Results From BRIGHT AML 1003

Endpoint/Study Population DAURISMO With

Low-Dose Cytarabine

Low-Dose Cytarabine Alone

OS N=77 N=38

Median survival, months (95% CI) 8.3 (4.4, 12.2) 4.3 (1.9, 5.7)

Hazard ratio (95% CI)

0.46 (0.30, 0.71)

p-value

0.0002

CR N=14 N=1

CR rate (in %, 95% CI) 18.2 (10.3, 28.6) 2.6 (0.1, 13.8)

Abbreviations: AML = acute myeloid leukemia; N = number of patients; OS = overall survival; CI = confidence interval; CR = complete response.

Hazard ratio (DAURISMO with low-dose cytarabine/low-dose cytarabine alone) based on the Cox Proportional hazards model stratified by

cytogenetic risk.

1-sided p-value from log-rank test stratified by cytogenetic risk.

Reference ID: 4353045

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For current labeling information, please visit https://www.fda.gov/drugsatfda

Figure 1. BRIGHT AML 1003 – Kaplan-Meier Plot of Overall Survival for Patients with AML

Abbreviations: CI = confidence interval; OS = overall survival; LDAC = low-dose cytarabine.

16 HOW SUPPLIED/STORAGE AND HANDLING

DAURISMO is supplied in the following strengths and package configurations:

DAURISMO fil

-coated tablets

Packa

e Confi

uratio

Tablet Stren

th (m

) NDC Print(description)

30 count bottle

100

0069-1531-30

100 mg strength: 11 mm

round, pale orange

film-coated tablet

debossed with “Pfizer”

on one side and “GLS

100” on the other

60 count bottle

25 m

0069-0298-60

25 mg strength: 7 mm

round, yellow

film-coated tablet

debossed with “Pfizer”

on one side and “GLS

25” on the other

Store at 20

C to 25

C (68

F to 77

F); excursions permitted between 15

C to 30

C (59

F to 86

F).

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Advise patients of the risks of DAURISMO treatment:

Reference ID: 4353045

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Embryo-Fetal Toxicity

 Advise female patients of the potential risk to a fetus and to inform their healthcare provider of a known

or suspected pregnancy. Advise female patients and female partners of male patients to contact their

healthcare provider with a known or suspected pregnancy [see Warnings and Precautions (5.1), Use in

Specific Populations (8.1, 8.3)].

Females and Males of Reproductive Potential

 Advise females of reproductive potential to use effective contraception during treatment with

DAURISMO and for at least 30 days after the last dose.

 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 [see Use in Specific Populations (8.3)].

Semen Donation

 Advise males not to donate semen during treatment with DAURISMO and for at least 30 days after the

last dose of DAURISMO[see Use in Specific Populations (8.3)].

Lactation

 Advise women not to breastfeed during treatment with DAURISMO and for at least 30 days after the

last dose of DAURISMO [see Use in Specific Populations (8.2)].

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 of DAURISMO [see Warnings and Precautions (5.1)].

Infertility

 Advise males of reproductive potential of the potential for impaired fertility from DAURISMO. Advise

male patients to seek advice on effective fertility preservation before treatment [see Use in Specific

Populations (8.3), Nonclinical Toxicology (13.1)].

QT Interval Prolongation

 Inform patients of signs and symptoms that may be indicative of significant QT interval prolongation.

Advise patients to contact their healthcare provider immediately in the event of syncope, pre-syncopal

symptoms, and cardiac palpitations [see Warnings and Precautions (5.2)].

This product’s label may have been updated. For current full prescribing information, please visit

www.DAURISMO.com.

LAB-1284-0.6

Reference ID: 4353045

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

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:

 You should talk to your healthcare provider about the risks of DAURISMO to your unborn child.

 Your healthcare provider will do a pregnancy test within 7 days before you start taking DAURISMO.

 You should not use DAURISMO during pregnancy.

 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.

 Talk to your healthcare provider right away if you have unprotected sex or if you think that your birth control has

failed.

 Tell your healthcare provider right away if you become pregnant or think that you may be pregnant.

For males:

 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:

 are 75 years of age or older, or

 have other medical conditions that prevent the use of standard chemotherapy

DAURISMO has not been studied in people with severe kidney problems or moderate-to-severe liver problems.

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:

 have heart problems, including a condition called long QT syndrome.

 abnormal blood salt (electrolytes) levels.

 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.

Reference ID: 4353045

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

How should I take DAURISMO?

 Take DAURISMO with the medicine cytarabine exactly as your healthcare provider tells you.

 Take DAURISMO 1 time each day, at about the same time each day.

 Take DAURISMO with or without food.

 Do not chew, split or crush DAURISMO tablets.

 If you miss a dose, 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.

 If you vomit after taking a dose of DAURISMO, do not take an extra dose, just take your next dose at your regular

time.

 Your healthcare provider will perform certain tests to check you for side effects before and during treatment with

DAURISMO.

 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.

What should I avoid while taking DAURISMO?

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

dose.

 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:

 See “What is the most important information I should know about DAURISMO?”

 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.

The most common side effects of DAURISMO with cytarabine include:

 low red blood cell count (anemia)



low platelet count

 tiredness



shortness of breath

 bleeding



decreased appetite

 fever with low white blood cell count

 muscle pain

 nausea

 swellin

of arms or le



changes in taste



pain or sores in your mouth or throat



constipation



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?

 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,

macro

ol, triacetin, iron oxide

ellow, and iron oxide red.

Reference ID: 4353045

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

LAB-1285-0.6

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. Issued: November 2018

Reference ID: 4353045

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda