Drug Interaction Report

MONITOR: Treatment with pegvisomant may increase glucose tolerance in some diabetic patients, potentially reducing their requirements for insulin and other antidiabetic agents. The mechanism is pegvisomant antagonism of endogenous growth hormone, the latter of which normally decreases insulin sensitivity and opposes the effects of insulin on carbohydrate metabolism. However, clinically relevant hypoglycemia was not observed in diabetic patients who were treated with pegvisomant in premarketing trials.

MANAGEMENT: Close clinical monitoring of glycemic control is recommended when pegvisomant is used in patients receiving insulin or other antidiabetic agents, and the dosages of these agents adjusted as necessary. Likewise, patients may be at risk for hyperglycemia when pegvisomant is withdrawn from their therapeutic regimen.

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.