Drug Interaction Report

ADJUST DOSING INTERVAL: Administration of vericiguat with food reduces its pharmacokinetic variability and increases its exposure. Vericiguat is less soluble at neutral pH than at acidic pH. Administration of vericiguat with a high-fat, high-calorie meal or low-fat, high-carbohydrate meal increased time to reach peak plasma concentration (Tmax) from about 1 hour (fasted) to about 4 hours (fed) and increased vericiguat systemic exposure (AUC) by 19% and peak plasma concentration (Cmax) by 9% for the 5 mg tablet and by 44% (AUC) and 41% (Cmax) for the 10 mg tablet as compared with the fasted state. Concurrent treatment with drugs that increase gastric pH, such as proton pump inhibitors or antacids, decrease vericiguat AUC by about 30%. Co-treatment with drugs that increase gastric pH did not affect vericiguat exposure in patients with heart failure when vericiguat was taken as directed with food.

MANAGEMENT: Administer vericiguat with food to ensure maximal exposure and decrease pharmacokinetic variability.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.