Drug Interaction Report

MONITOR: Coadministration of zidovudine with other bone marrow depressive or cytotoxic agents may increase the risk and/or severity of zidovudine hematologic toxicity. Zidovudine has been associated with hematologic toxicities such as: neutropenia, granulocytopenia and severe anemia that required blood transfusions particularly in patients with advanced HIV disease.

MANAGEMENT: Hematological parameters should be closely monitored. Some authorities recommend dosages of one or both agents may be adjusted if necessary.

MONITOR: The concomitant or sequential administration of multiple antineoplastic agents may result in additive toxicities, particularly in the bone marrow, gastrointestinal tract and heart.

MANAGEMENT: Close clinical and laboratory monitoring for hematologic and nonhematologic toxicities are recommended when antineoplastic agents are administered concurrently or during close intervals. Dosing adjustments may be necessary. The manufacturers' recommendations and institutional protocols for dosage, treatment regimens, monitoring, and management of toxicities should be consulted.

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.