Drug Interaction Report

ADJUST DOSE: There is no evidence that cidofovir affects the pharmacokinetics of zidovudine. However, probenecid, which is given in conjunction with cidofovir, reduces the metabolic clearance of zidovudine.

MANAGEMENT: Zidovudine therapy should be temporarily discontinued, or the zidovudine dose should be reduced by 50%, on days when cidofovir and probenecid are administered. The usual zidovudine therapy may be resumed on days when the patient is not receiving cidofovir and probenecid.

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.