Drug Interaction Report

GENERALLY AVOID: Concomitant use of the cytidine analog nucleoside reverse transcriptase inhibitors (NRTI) lamivudine and emtricitabine may inhibit the intracellular phosphorylation of one another to their respective active derivative in vivo. This could result in diminished antiretroviral effects of these drugs. However, clinical experience on the coadministration of cytidine analogs is lacking. This interaction may also occur with zalcitabine. In addition, the therapeutic efficacy of these drugs in combination appears limited, since lamivudine and emtricitabine have similar resistance profiles via mutation of the same viral reverse transcriptase gene (M184V).

MANAGEMENT: The use of the cytidine analog NRTIs lamivudine, emtricitabine, or zalcitabine in any combination in an antiretroviral treatment regimen that consists of two NRTIs is not recommended. Local antiretroviral treatment experts should be consulted for current practice.

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.

Zalcitabine bioavailability may be decreased by 14% if taken with meals. The mechanism and clinical significance are unknown.