DAURISMO™ (glasdegib) 6 ADVERSE REACTIONS

(glasdegib)

Prescribing Information

6 ADVERSE REACTIONS

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)]

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 3.

Table 3. Adverse Reactions Occurring in ≥10% of Patients*† 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 %
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. Þ Chest pain includes chest pain and non-cardiac chest pain. ß Musculoskeletal pain includes pain in extremity, arthralgia, back pain, myalgia, musculoskeletal pain, musculoskeletal chest pain, neck pain, and bone pain. à Muscle spasms includes muscle spasms and muscle tightness. è Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower. ð Diarrhea includes diarrhea, colitis, and gastroenteritis. ø Dyspnea includes dyspnea, hypoxia, bronchospasm, and respiratory failure. ý Cough includes cough and productive cough. £ Dysgeusia includes dysgeusia and ageusia. ¥ Rash includes rash, pruritus, erythema, skin ulcer, rash maculo-papular, and rash pruritic. Œ Pneumonia includes pneumonia, pneumonia aspiration, and lung infection. œ Atrial arrhythmia includes atrial fibrillation, bradycardia, tachycardia, and sinus tachycardia. Ɖ Renal insufficiency includes acute kidney injury, blood creatinine increased, oliguria, and renal failure.
Blood and lymphatic system disorder	Anemia	43	41	42	37
	Hemorrhage‡	36	6	42	12
	Febrile neutropenia	31	31	22	22
	Thrombocytopenia	30	30	27	24
General disorders and administration site conditions	Fatigue§	36	14	32	7
	Edema¶	30	0	20	2
	Mucositis#	21	1	12	0
	Pyrexia	18	1	22	2
	Chest painÞ	12	1	2	0
Musculoskeletal and connective tissue disorders	Musculoskeletal painß	30	2	17	2
Musculoskeletal and connective tissue disorders	Muscle spasmà	15	0	5	0
Gastrointestinal disorders	Nausea	29	1	12	2
	Constipation	20	1	12	0
	Abdominal painè	19	0	12	0
	Diarrheað	18	4	22	0
	Vomiting	18	2	10	2
Respiratory thoracic and mediastinal disorders	Dyspneaø	23	11	24	7
Respiratory thoracic and mediastinal disorders	Coughý	18	0	15	2
Metabolism and nutrition disorders	Decrease appetite	21	1	7	2
Nervous system disorders	Dysgeusia£	21	0	2	0
	Dizziness	18	1	7	0
	Headache	12	0	10	2
Skin and subcutaneous tissue disorders	Rash¥	20	2	7	2
Infection and infestations	PneumoniaŒ	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 arrhythmiaœ	13	4	7	2
Renal and urinary disorders	Renal insufficiencyƉ	19	5	10	0

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.

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 4.

Table 4. Selected Laboratory Abnormalities (≥15%)* Within the First 90 Days of Therapy in BRIGHT AML 1003
	DAURISMO with Low-Dose Cytarabine			Low-Dose Cytarabine
Laboratory Abnormality	N	All Grades %	Grade 3 or 4† %	N	All Grades %	Grade 3 or 4† %
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.
* Maximum severity based on the number of patients with available on-study laboratory data. † Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening.
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 increased	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

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).

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:

•: 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.

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.
•: have muscle pain or spasms.
•: have kidney problems.
•: 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?

•: 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 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.
•: 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.
•: 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?

•: 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.
•: 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:

•: low red blood cell count (anemia)
•: tiredness
•: bleeding
•: fever with low white blood cell count
•: muscle pain
•: swelling of arms or legs
•: low platelet count

•: nausea
•: shortness of breath
•: decreased appetite
•: 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, 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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