Drug Interactions between boceprevir and levamlodipine

MONITOR: Coadministration with the hepatitis C virus (HCV) NS3/4A protease inhibitors, boceprevir and telaprevir, may increase the plasma concentrations and pharmacologic effects of calcium channel blockers, especially the dihydropyridines (e.g., amlodipine, felodipine, nicardipine, nifedipine, nisoldipine). The mechanism involves inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of most calcium channel blockers. In 19 study subjects, administration of a single 5 mg dose of amlodipine during treatment with telaprevir (750 mg every 8 hours for 7 days) increased the amlodipine peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 27% and 179%, respectively, compared to administration alone. No data are available for boceprevir; however, a similar interaction is expected.

MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if calcium channel blockers are used in combination with boceprevir or telaprevir. Dosage reduction may be required for the calcium channel blocker, particularly if it is a dihydropyridine. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.