Drug Interaction Report

MONITOR: Clearance of hepatitis C virus (HCV) infection with direct acting antiviral agents (DAAs) may lead to changes in hepatic function which may result in altered blood glucose control. Serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. These cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment.

MANAGEMENT: Blood glucose should be closely monitored during treatment of HCV with DAAs, particularly during the first 3 months, and appropriate changes made to the antidiabetic drug regimen as needed. The patient as well as the healthcare providers in charge of diabetic care should be apprised of the risk of hypoglycemia. Patients should be aware of the potential signs and symptoms of hypoglycemia such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. For antidiabetic medications that are not glucose-dependent, reduction in the dosage should be considered to mitigate the risk of hypoglycemia.

ADJUST DOSING INTERVAL: Pramlintide slows gastric emptying and may delay the absorption of concomitantly administered oral medications. In a pharmacokinetic study of 24 patients with type 2 diabetes, coadministration with pramlintide (120 mcg) decreased the peak plasma concentration (Cmax) of acetaminophen (1000 mg) by 29% and increased its time to peak plasma concentration (Tmax) based on the time of acetaminophen administration relative to pramlintide injection. Pramlintide significantly increased acetaminophen Tmax (range 48 to 72 minutes) when acetaminophen was administered simultaneously with or up to 2 hours following pramlintide injection, but it had negligible effect when acetaminophen was administered 1 to 2 hours before pramlintide injection.

MANAGEMENT: When rapid onset of a concomitantly administered oral medication is critical to its effectiveness, the medication should be administered at least 1 hour before or 2 hours after pramlintide injection.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of simeprevir, although the type of food does not seem to matter. In healthy study subjects, administration of simeprevir after a high-fat, high-caloric (928 kcal) breakfast increased systemic exposure (AUC) by 61% and delayed absorption by 1 hour, while administration after a normal caloric (533 kcal) breakfast increased AUC by 69% and delayed absorption by 1.5 hours.

MANAGEMENT: To ensure maximal oral absorption, simeprevir should be administered with food.