Daurismo

Last updated on RxList: 1/21/2021
Daurismo Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Daurismo?

Daurismo (glasdegib) 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 older or who have comorbidities that preclude use of intensive induction chemotherapy.

What Are Side Effects of Daurismo?

Common side effects of Daurismo include:

Dosage for Daurismo

The recommended dose of Daurismo is 100 mg orally, once daily.

What Drugs, Substances, or Supplements Interact with Daurismo?

Daurismo may interact with strong CYP3A inhibitors or inducers, and QTc prolonging drugs. Tell your doctor all medications and supplements you use.

Daurismo During Pregnancy and Breastfeeding

Daurismo is not recommended for use during pregnancy; it can harm a fetus. Pregnancy testing in female patients of reproductive potential is conducted prior to initiating Daurismo treatment. Females of reproductive potential are advised to use contraception during treatment with Daurismo and for at least 30 days after the last dose. Male patients with female partners should also 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. Breastfeeding is not recommended while using Daurismo and for at least 30 days after the last dose.

Additional Information

Our Daurismo (glasdegib) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Daurismo Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • irregular or fast heartbeats, shortness of breath, and sudden dizziness (like you might pass out);
  • easy bruising, unusual bleeding, purple or red spots under your skin;
  • low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed, cold hands and feet; or
  • low white blood cell counts--fever, chills, mouth sores, skin sores, sore throat, cough, trouble breathing.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • bleeding, low platelet count;
  • fever, low blood cell counts;
  • mouth sores, changes in your sense of taste;
  • loss of appetite, constipation, nausea;
  • rash;
  • muscle pain;
  • swelling in your arms or legs;
  • feeling tired; or
  • trouble breathing.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Daurismo (Glasdegib Tablets)

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Daurismo Professional Information

SIDE EFFECTS

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

  • QT Interval Prolongation [see WARNINGS AND PRECAUTIONS]

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]. 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 Patientsa,b Within the First 90 Days of Therapy in BRIGHT AML 1003

Body SystemAdverse ReactionsDAURISMO With Low-Dose Cytarabine
N=84
Low-Dose Cytarabine
N=41
All Grades %Grade ≥ 3 %All Grades %Grade ≥ 3 %
Blood and lymphatic system disorderAnemia43414237
Hemorrhagec3664212
Febrile neutropenia31312222
Thrombocytopenia30302724
General disorders and administration site conditionsFatigued3614327
Edemae300202
Mucositisf211120
Pyrexia181222
Chest paing12120
Musculoskeletal andMusculoskeletal painh302172
connective tissue disordersMuscle spasmi15050
Gastrointestinal disordersNausea291122
Constipation201120
Abdominal painj190120
Diarrheak184220
Vomiting182102
Respiratory thoracic andDyspneal2311247
mediastinal disordersCoughm180152
Metabolism and nutrition disordersDecrease appetite21172
Nervous system disordersDysgeusian21020
Dizziness18170
Headache120102
Skin and subcutaneous tissue disordersRasho20272
Infection and infestationsPneumoniap19152422
InvestigationsHyponatremia11600
Platelet count decreased15151010
Weight decreased13020
White blood cell count decreased111152
Cardiac disordersAtrial arrhythmiaq13472
Renal and urinary disordersRenal insufficiencyr195100
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.
a Adverse reactions with ≥10% incidence in the DAURISMO with low-dose cytarabine arm or the low-dose cytarabine arm are included.
b No Grade 5 events in the DAURISMO with low-dose cytarabine or low-dose cytarabine alone arm.
c 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.
d Fatigue includes asthenia and fatigue.
e Edema includes edema peripheral, edema, fluid overload, fluid retention, and swelling face.
f Mucositis includes mucosal inflammation, oropharyngeal pain, stomatitis, anal ulcer, gingival pain, laryngeal inflammation, esophagitis, oral pain, aphthous ulcer, mouth ulceration, and pharyngeal inflammation.
g Chest pain includes chest pain and non-cardiac chest pain.
h Musculoskeletal pain includes pain in extremity, arthralgia, back pain, myalgia, musculoskeletal pain, musculoskeletal chest pain, neck pain, and bone pain.
i Muscle spasms includes muscle spasms and muscle tightness.
j Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower.
k Diarrhea includes diarrhea, colitis, and gastroenteritis.
l Dyspnea includes dyspnea, hypoxia, bronchospasm, and respiratory failure.
m Cough includes cough and productive cough.
n Dysgeusia includes dysgeusia and ageusia.
o Rash includes rash, pruritus, erythema, skin ulcer, rash maculo-papular, and rash pruritic.
p Pneumonia includes pneumonia, pneumonia aspiration, and lung infection.
q Atrial arrhythmia includes atrial fibrillation, bradycardia, tachycardia, and sinus tachycardia.
r 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.

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%)a Within the First 90 Days of Therapy in BRIGHT AML 1003

Laboratory AbnormalityDAURISMO with Low-Dose CytarabineLow-Dose Cytarabine
NAll Grades %Grade 3 or 4* %NAll Grades %Grade 3 or 4* %
Creatinine increased8196140805
Hyponatremia8154739418
Hypomagnesemia8133039230
AST increased8028140230
Blood bilirubin increased8025439333
ALT increased8024040283
Alkaline phosphatase increased8023040283
Hyperkalemia811614083
CPK increased381601760
Hypokalemia8115040230
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.
aMaximum 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).

Read the entire FDA prescribing information for Daurismo (Glasdegib Tablets)

© Daurismo Patient Information is supplied by Cerner Multum, Inc. and Daurismo Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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