n patients with newly-diagnosed AMLand other conditions for which DAURISMO is not indicated in the clinical trial are shown in Table 3.
Table 3. Selected Laboratory Abnormalities (≥ 15% )a Within the First 90 Days of Therapy in BRIGHT
AML 1003
Laboratory Abnormality
DAURISMO with Low-Dose
Cytarabine Low-Dose Cytarabine
N All Grades
%
Grade 3 or 4*
% N 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
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
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.
a. 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) afterthe first 90 days of therapy in BRIGHT AML 1003:
hypophosphatemia (8 in 38 patients), creatinine increased (2 in 39 patients), and ALT increased (2 in40 patients).
7 DRUG INTERACTIONS
Table 4. Drug Interactions with DAURISMO
Strong CYP3A Inhibitors
Clinical Impact Co-administration of DAURISMO with strong CYP3A inhibitorsincreased glasdegib plasma concentrations [see Clinical
Pharmacology (12.3)].
Increased glasdegib concentrations may increase the risk of adversereactions including QTc interval prolongation [see Warnings andPrecautions (5.2)].
Prevention or
Management
Consider alternative therapies that are not strong CYP3A4 inhibitorsduring treatment with DAURISMO.
Monitor patients for increased risk of adverse reactions includingQTc interval prolongation [see Warnings and Precautions (5.2)].Strong CYP3A InducersClinical Impact Co-administration of DAURISMO with strong CYP3A inducersdecreased 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 mayincrease the risk of QTc interval prolongation [see Warnings andPrecautions (5.2)].
Prevention or
Management
Avoid co-administration of QTc prolonging drugs with DAURISMOor replace with alternative therapies.
If co-administration of a QTc prolonging drug is unavoidable, monitorpatients for increased risk of QTc interval prolongation [see Warningsand 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-associatedrisk of major birth defects and miscarriage. DAURISMO is not recommended for use during pregnancy.
Conduct pregnancy testing in female patients of reproductive potential |
