Daurismo glasdegib 100 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Hedgehog Pathway Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Glasdegib is used along with cytarabine as a first treatment for acute myeloid leukemia (AML; a type of cancer that begins in the white blood cells) in people over 75 years of age, or in adults who have other medical conditions and can not be treated with other chemotherapy medications. Glasdegib is in a class of medications called hedgehog pathway inhibitors. It works by blocking the action of a protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells.
Read the full MedlinePlus article ↗- Daurismo is a treatment for a type of blood cancer called acute myeloid leukemia, or AML. It's specifically approved for people who are 75 or older, or who have other health condit...
- What is Daurismo actually for, and why is it combined with another medicine?
- You take Daurismo as a tablet by mouth once a day — you can take it with or without food, whichever works for you. The key things to remember are: swallow it whole (don't split or...
- How do I take Daurismo, and does it matter if I take it with food?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Glasdegib — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII AG9B65PV6B
A starch derivative made from corn that helps tablets and capsules break apart quickly when swallowed. It acts as a disintegrant, allowing the medicine to dissolve and be absorbed in your stomach and intestines.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII XHX3C3X673
Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
11 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $777.56 | $23,326.74 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Daurismo 100 mgthis 00069-1531-30 | Pfizer | 30 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11168066 ↗ | Method of use | U-3254 | Apr 13, 2036 |
| US 11168066 ↗ | Method of use | U-3254 | Apr 13, 2036 |
| US 11891372 ↗ | Method of use | U-3254 | Apr 13, 2036 |
| US 11891372 ↗ | Method of use | U-3254 | Apr 13, 2036 |
| US 8148401 ↗ | Drug substance | — | Nov 21, 2032 |
| US 10414748 ↗ | Drug substance | — | Apr 13, 2036 |
| US 8431597 ↗ | Drug product | — | Jun 29, 2028 |
| US 8431597 ↗ | Drug product | — | Jun 29, 2028 |
| US 8148401 ↗ | Drug substance | — | Nov 21, 2032 |
| US 10414748 ↗ | Drug substance | — | Apr 13, 2036 |
Is there a generic version of DAURISMO 100 MG TABLET?
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00069-1531-30 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (0069-1531-30) | 2018-12-10 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
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) ] .
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 Usage ▾
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. 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 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended dosage: 100 mg orally once daily. ( 2.1 )
2.1Recommended Dosage and Schedule The recommended dosage of DAURISMO is 100 mg orally once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control. For patients without unacceptable toxicity, treat for a minimum of 6 cycles to allow time for clinical response. Administer DAURISMO with or without food.
Do not split or crush DAURISMO tablets. Administer DAURISMO about the same time each day. If a dose of DAURISMO is vomited, do not administer a replacement dose; wait until the next scheduled dose is due.
If a dose of DAURISMO is missed or not taken at the usual time, administer the dose as soon as possible and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses of DAURISMO within 12 hours.
2.2Monitoring and Dosage Modifications Assess complete blood counts, electrolytes, renal, and hepatic function prior to the initiation of DAURISMO and at least once weekly for the first month. Monitor electrolytes and renal function once monthly for the duration of therapy. Obtain creatine phosphokinase (CPK) levels prior to initiating DAURISMO and as indicated clinically thereafter (e.g., if muscle symptoms are reported).
Monitor electrocardiograms (ECGs) prior to the initiation of DAURISMO, approximately one week after initiation, and then once monthly for the next two months to assess for QTc prolongation. 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 dosage modification guidelines for patients who develop an adverse reaction. Table 1.
Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Recommended Action Abbreviations: CPK = creatine phosphokinase, ULN = upper limit of normal. QTc interval prolongation on at least 2 separate electrocardiograms (ECGs) [see Warnings and Precautions (5.2) ] 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 than 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) ] .
Interrupt DAURISMO. Resume DAURISMO at a reduced dosage 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 dosage 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. Musculoskeletal adverse reactions [see Warnings and Precautions (5.3) ] Grade 3 Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. or serum CPK elevation between 2.5 and 10 times upper limit of normal (ULN) Obtain CPK and serum creatinine levels at least weekly until resolution of clinical signs and symptoms.
Interrupt DAURISMO until symptoms reduce to mild or return to baseline. Resume DAURISMO at the same dose level, or at a reduced dose of 50 mg. If toxicity recurs, discontinue DAURISMO.
Grade 4 or serum CPK elevation greater than 10 times ULN Discontinue DAURISMO. Hematologic toxicity [see Adverse Reactions (6.1) ] Platelets less than 10 Gi/L for more than 42 days in the absence of disease Discontinue DAURISMO and low-dose cytarabine per…
💊 Dosage Forms and Strengths ▾
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. Tablets: 100 mg, 25 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 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 ) • Musculoskeletal Adverse Reactions: Obtain creatine phosphokinase (CPK) and serum creatinine levels prior to initiating DAURISMO and as indicated clinically thereafter. Temporary dose interruption, dose reduction, or discontinuation of DAURISMO may be required for musculoskeletal adverse reactions or serum CPK elevation. ( 2.2 , 5.3 )
5.1Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal embryo-fetal developmental toxicity studies, DAURISMO can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. There are no clinical data on the use of DAURISMO in pregnant women. In animal embryo-fetal developmental toxicity studies, glasdegib caused embryotoxicity, fetotoxicity and teratogenicity at maternal exposures that were less than the human exposure at the recommended human dose of 100 mg [see Use in Specific Populations (8.1 , 8.2) , Clinical Pharmacology (12.1) ] .
Advise pregnant women of the potential risk to the fetus. Females of Reproductive Potential DAURISMO is not recommended for use during pregnancy. Conduct pregnancy testing in female patients of reproductive potential prior to initiating DAURISMO treatment.
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.
5.2QTc 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) ] .
5.3Musculoskeletal Adverse Reactions Musculoskeletal adverse reactions, which may be accompanied by CPK elevations, have occurred with DAURISMO and other drugs which inhibit the hedgehog (Hh) path…
🤒 Adverse Reactions ▾
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) ] Most common adverse reactions (incidence ≥20%) are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 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. 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.
Blood and lymphatic system disorder Anemia 43 41 42 37 Hemorrhage Hemorrhage includes petechiae, epistaxis, hematoma, contusion, rectal hemorrhage, anal hemorrhage, ecchymosis, gingival bleeding, hematuria, mouth hemorrhage, purpura, cerebral hemorrhage, eye contusion, eye hemorrha…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 5. 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 and Moderate CYP3A Inducers Clinical Impact Co-administration of DAURISMO with strong and moderate CYP3A inducers decreased glasdegib plasma concentrations [see Clinical Pharmacology (12.3) ] . • Decreased glasdegib concentrations may reduce efficacy. Prevention or Management • Avoid co-administration of DAURISMO with strong and moderate CYP3A4 inducers. • If co-administration of DAURISMO with moderate CYP3A4 inducers cannot be avoided, increase the dose of DAURISMO [see Dosage and Administration (2.3) ] . 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) ]. • Strong CYP3A4 Inhibitors: Consider alternative therapies that are not strong CYP3A4 inhibitors or monitor for increased risk of adverse reactions, including QTc interval prolongation. ( 7 ) • Strong CYP3A4 Inducers: Avoid concomitant use with DAURISMO.
( 7 ) • Moderate CYP3A4 Inducers: Avoid concomitant use with DAURISMO. If, concomitant use cannot be avoided, increase the dose of DAURISMO. ( 2.3 , 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 ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed. ( 8.2 )
8.1Pregnancy 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 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.
8.2Lactation 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.
8.3Females 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…
🤰 Pregnancy ▾
8.1Pregnancy 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 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.
🧒 Pediatric Use ▾
8.4Pediatric 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.
🧓 Geriatric Use ▾
8.5Geriatric 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.
🆘 Overdosage ▾
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 reactions that were dose limiting were nausea, vomiting, dehydration, hypotension, fatigue, and dizziness.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics 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.
12.3Pharmacokinetics DAURISMO at 5 mg to 600 mg once daily (0.05 to 6 times the recommended dose) result in a dose proportional increase in glasdegib peak concentrations (C max ) and area under the curve over the dosing interval (AUC 0-Tau ). Steady-state plasma levels are reached by 8 days of daily dosing. 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 0-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 0-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 z /F) was 188 L (20%) in patients with hematologic malignancies.
Elimination Glasdegib has a mean (± SD) half-life of 17.4 h (3.7) and geometric mean (%CV) apparent clearance of
6.45L/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 × ULN and any AST), and mild renal impairment (creatinine clearance 60–89 mL/min) did not have clinically meaningful effects on the pharmacokinetics of glasdegib.
Patients with Renal Impairment Following administration of a single dose of DAURISMO 100 mg, glasdegib AUC 0-INF increased by 2.1-fold in subjects with moderate (eGFR 30 to 59 mL/min) and severe (eGFR 15 to 29 mL/min) renal impairment compared to subjects with normal renal function (eGFR ≥90 mL/min). The pharmacokinetics of glasdegib have not been studied in patients with end stage renal disease requiring hemodialysis. Patients with Hepatic Impairment Following administration of a single dose of DAURISMO 100 mg, glasdegib AUC 0-INF increased by 11% in subjects with moderate hepatic impairment (Child-Pugh B)…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING DAURISMO is supplied in the following strengths and package configurations: DAURISMO film-coated tablets Package Configuration Tablet Strength (mg) NDC Print (description) 30 count bottle 100 mg 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 mg 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).
📦 Storage and Handling ▾
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).
📋 Description ▾
11 DESCRIPTION DAURISMO (glasdegib) is a hedgehog pathway inhibitor. It is formulated with the maleate salt of glasdegib. The molecular formula for glasdegib maleate is C 25 H 26 N 6 O 5 .
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. 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.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). 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) ] . QTc Interval Prolongation • Inform patients of signs and symptoms that may be indicative of significant QTc 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) ]. Musculoskeletal Adverse Reactions • Advise patients starting therapy with DAURISMO of the risk of muscle-related adverse reactions. • Advise patients to report promptly any new unexplained muscle pain, tenderness, or weakness occurring during treatment or that persists after discontinuing DAURISMO [see Warnings and Precautions (5.3) ] .
💬 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 tr…