42 6 35 2.7
Chemistry
Hypoalbuminemia 44 0 34 0
Increased ALT 40 1.4 63 13
Hyperglycemia 36 1.0 38 2.5
Increased AST 35 0.5 57 8
Hypocalcemia 33 1.4 28 2.0
Hypokalemia 29 7 18 2.0
Hyponatremia 26 2.9 20 1.5
Increased creatinine 24 0 16 0.5
Increased alkaline phosphatase 22 0.5 21 2.0
Hypomagnesemia 22 0.5 9 0
Hyperbilirubinemia 16 0.5 22 0.5
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on VIZIMPRO
Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce VIZIMPRO efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours after taking an H2-receptor antagonist [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].
7.2 Effect of VIZIMPRO on CYP2D6 Substrates
Concomitant use of VIZIMPRO increases the concentration of drugs that are CYP2D6 substrates [see Clinical Pharmacology (12.3)] which may increase the risk of toxicities of these drugs. Avoid concomitant use of VIZIMPRO with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action, VIZIMPRO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on VIZIMPRO use in pregnant women. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss and reduced fetal body weight at doses resulting in exposures near the exposure at the 45 mg human dose (see Data). The absence of EGFR signaling has been shown to result in embryolethality as well as post-natal death in animals (see Data). Advise pregnant women of the potential risk to a fetus [see Use in Special Populations (8.3)].
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
Daily oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss, maternal toxicity, and reduced fetal body weight at 5 mg/kg/day (approximately 1.2 times the exposure based on area under the curve [AUC] at the 45 mg human dose).
Disruption or depletion of EGFR in mouse models has shown EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/post-natal survival and development. Reduction or elimination of embryo-fetal or maternal EGFR signaling in mice can prevent implantation, and can cause embryo-fetal loss during various stages of gestation (through effects on placental development), developmental anomalies, early death in surviving fetuses, |
