Drug Interaction Report

MONITOR: Drugs that affect renal function and/or hydration status may potentiate the adverse renal effects of exenatide. The mechanism of interaction is unknown. Exenatide has not been found to be directly nephrotoxic in preclinical or clinical studies. However, there have been reports of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure during postmarketing use. In some cases, hemodialysis or kidney transplantation was required. Some of these events occurred in patients receiving one or more pharmacologic agents known to affect renal function or hydration status (e.g., ACE inhibitors, nonsteroidal anti-inflammatory drugs, diuretics), and some occurred in patients who had been experiencing nausea, vomiting or diarrhea, with or without dehydration. Most cases were reversible with supportive treatment and discontinuation of potentially causative agents, including exenatide.

MANAGEMENT: Clinicians should be aware of the potential for increased adverse renal effects of exenatide during coadministration with drugs that are known to affect renal function or hydration status.

ADJUST DOSING INTERVAL: Exenatide slows gastric emptying and may reduce the extent and rate of absorption of concomitantly administered oral medications. When acetaminophen 1000 mg was administered simultaneously with exenatide 10 mcg and also one hour, 2 hours, and 4 hours after exenatide injection, acetaminophen systemic exposure (AUC) was decreased by 21%, 23%, 24%, and 14%, respectively; peak plasma concentration (Cmax) was decreased by 37%, 56%, 54%, and 41%, respectively; and time to peak plasma concentration (Tmax) was increased from 0.6 hours in the control period to 0.9 hours, 4.2 hours, 3.3 hours, and 1.6 hours, respectively. These values were not significantly changed when acetaminophen was given one hour before exenatide injection.

MANAGEMENT: Concomitantly administered oral medications that are dependent on threshold concentrations for efficacy (e.g., antibiotics, contraceptives) or that require rapid gastrointestinal absorption (e.g., hypnotics, pain medications) should be administered at least 1 hour before exenatide. If such medications are to be administered with food, patients should be advised to take them with a meal or snack when exenatide is not administered.