Drug Interaction Report

GENERALLY AVOID: Sorbitol may decrease the serum concentration of lamivudine. The mechanism of interaction has not been established. In an open-label, randomized sequence, 4-period, crossover study of 16 healthy adult subjects, a single 300 mg dose of lamivudine oral solution was administered alone or in combination with a single 3.2 g, 10.2 g, or 13.4 g dose of sorbitol oral solution. Coadministration of lamivudine with sorbitol resulted in dose-dependent decreases in lamivudine AUC (14%, 32%, and 36%) and Cmax (28%, 52%, and 55%).

MANAGEMENT: When possible, avoid use of lamivudine with products that contain osmotic polyalcohols (e.g., sorbitol) or monosaccharide alcohols (e.g., lactitol, mannitol). If coadministration cannot be avoided, more frequent monitoring of viral load should be considered.

ADJUST DOSING INTERVAL: Lactitol may decrease the absorption of concomitantly administered oral medications.

MANAGEMENT: Lactitol should be administered at least 2 hours before or 2 hours after concomitant oral medications.

Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.