Vizimpro Drug Interactions

Co-administration of dacomitinib with agents that increase gastric pH: The aqueous solubility of dacomitinib is pH dependent, with low (acidic) pH resulting in higher solubility. Data from a study in 24 healthy subjects indicated that co-administration of a single 45 mg dacomitinib dose with the PPI rabeprazole 40 mg once daily for 7 days decreased dacomitinib C_max, AUC_0-96h (area under the concentration-time curve from time 0 to 96 hours), and AUC_inf (AUC from time 0 to infinity) (n=14) by approximately 51%, 39%, and 29%, respectively, when compared to a single 45 mg dose of dacomitinib administered alone. PPIs should be avoided while receiving treatment with dacomitinib (see Precautions).
Based on data from observations in 8 patients in Study A7471001, there was no apparent effect of local antacid administration on C_max and AUC_inf of dacomitinib. Based on pooled data in patients, there was no apparent effect of histamine-2 (H2) receptor antagonists on steady-state trough concentration of dacomitinib (geometric mean ratio of 86% (90% CI: 73; 101). Local antacids and H2 receptor antagonists may be used if needed. Dacomitinib should be administered 2 hours before or at least 10 hours after taking H2 receptor antagonists.
Co-administration of dacomitinib and CYP2D6 substrates: Co-administration of single 45 mg oral dose of dacomitinib increased the mean exposure (AUC_last and C_max) of dextromethorphan, a probe CYP2D6 substrate, 855% and 874%, respectively, compared with administration of dextromethorphan alone. These results suggest that dacomitinib may increase exposure of other medicinal products (or decrease exposure to active metabolites) primarily metabolised by CYP2D6. Concomitant use of medicinal products predominantly metabolised by CYP2D6 should be avoided (see Precautions). If concomitant use of such medicinal products is considered necessary, they should follow their respective labels for dose recommendation regarding co-administration with strong CYP2D6 inhibitors.
Effect of dacomitinib on drug transporters: Based on in vitro data, dacomitinib may have the potential to inhibit the activity of P-glycoprotein (P-gp) (in the gastrointestinal [GI] tract), Breast Cancer Resistance Protein (BCRP) (systemically and GI tract), and organic cation transporter (OCT)1 at clinically relevant concentrations (see Pharmacology: Pharmacokinetics under Actions).