Drug Interactions between abacavir / lamivudine / zidovudine and rifabutin

MONITOR: Coadministration with rifamycins may decrease the plasma concentrations of zidovudine. The proposed mechanism is rifamycin induction of hepatic zidovudine glucuronidation and/or first-pass metabolism. In eight HIV-positive subjects, rifampicin (600 mg orally once a day for 14 days) decreased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and urine recovery of zidovudine (200 mg orally every 8 hours) by 43%, 47% and 37%, respectively, compared to administration of zidovudine alone. Zidovudine oral clearance increased by 89% and formation clearance to the glucuronide metabolite increased by 100% during combination treatment. Pharmacokinetic values returned to within 26% of baseline 14 days after stopping rifampicin. An earlier study comparing four HIV patients receiving the combination against a reference population of 69 patients receiving zidovudine without rifampicin revealed similar findings. Likewise, rifabutin also reportedly decreased zidovudine AUC by 32% and increased its clearance by 43% in one study. The interaction has not been investigated using rifapentine. However, in vitro and in vivo enzyme studies have suggested rifapentine induction potential to be less than that of rifampicin but greater than that of rifabutin.

MANAGEMENT: Clinicians may consider monitoring antiretroviral response more closely whenever a rifamycin is added to or withdrawn from therapy in patients stabilized on their existing HIV regimen. Most experts do not consider the interaction with rifamycins significant enough to warrant an empiric dosage adjustment of zidovudine when it is used as part of an effective antiretroviral regimen. However, interactions with other antiretroviral agents in the regimen (e.g., protease inhibitors, non-nucleoside reverse transcriptase inhibitors) may preclude the use of rifamycins, particularly rifampicin, or necessitate modification of the existing antiretroviral regimen. In general, treatment of tuberculosis (TB) in the context of antiretroviral therapy is complex and requires an individualized approach. Experts in the treatment of HIV-related TB should be consulted, and TB and HIV care providers should work in close coordination throughout treatment.