opmental outcomes in multiple organs in embryos/neonates.
8.2 Lactation
Risk Summary
There is no information regarding the presence of dacomitinib or its metabolites in human milk or their effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from VIZIMPRO, advise women not to breastfeed during treatment with VIZIMPRO and for at least 17 days after the last dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating VIZIMPRO [see Use in Specific Populations (8.1)].
Contraception
VIZIMPRO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Females
Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose.
8.4 Pediatric Use
The safety and effectiveness of VIZIMPRO in pediatrics have not been established.
8.5 Geriatric Use
Of the total number of patients (N=394) in five clinical studies with EGFR mutation-positive NSCLC who received VIZIMPRO at a dose of 45 mg orally once daily [ARCHER 1050 (N=227), Study A7471009 (N=38), Study A7471011 (N=83), Study A7471028 (N=16), and Study A7471017 (N=30)] 40% were 65 years of age and older.
Exploratory analyses across this population suggest a higher incidence of Grade 3 and 4 adverse reactions (67% versus 56%, respectively), more frequent dose interruptions (53% versus 45%, respectively), and more frequent discontinuations (24% versus 10%, respectively) for adverse reactions in patients 65 years or older as compared to those younger than 65 years.
8.6 Renal Impairment
No dose adjustment is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min estimated by Cockcroft-Gault). The recommended dose of VIZIMPRO has not been established for patients with severe renal impairment (CLcr <30 mL/min) [see Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
No dose adjustment is recommended in patients with mild (total bilirubin ≤ upper limit of normal [ULN] with AST > ULN or total bilirubin > 1 to 1.5 × ULN with any AST) or moderate (total bilirubin > 1.5 to 3 × ULN and any AST) hepatic impairment. The recommended dose of VIZIMPRO has not been established for patients with severe hepatic impairment (total bilirubin > 3 to 10 × ULN and any AST) [see Clinical Pharmacology (12.3)].
11 DESCRIPTION
Dacomitinib is an oral kinase inhibitor with a molecular formula of C24H25ClFN5O2 ∙ H2O and a molecular weight of 487.95 Daltons. The chemical name is: (2E)-N-{4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}-4-(piperidin-1-yl)but-2-enamide monohydrate and its structural formula is:
Chemical Structure
Dacomitinib is a white to pale yellow powder.
VIZIMPRO tablets contain 45, 30, or 15 mg of dacomitinib with the following inactive ingredients in the tablet core; lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, and magnesium stearate. The film coating consists of Opadry II® Blue 85F30716 containing: Polyvinyl alcohol – partially hydrolyzed, Talc, Titanium dioxide, Macrogol/PEG 3350, and FD&C Blue #2/Indigo Carmine Aluminum Lake.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Dacomitinib is an irreversib |
