The FDA and Roche notified healthcare providers about drug-induced hepatitis with marked transaminase elevations, which has occurred in healthy volunteers receiving rifampin 600 mg once daily in combination with ritonavir 100 mg/saquinavir 1,000 mg twice daily (ritonavir boosted saquinavir).
The report emerged from a Phase I trial in healthy volunteers during a 28-day study period. Among these subjects, transaminase elevations of up to more than 20 times the upper limit of normal values were noted, and one subject was admitted to the hospital with marked transaminase elevations. Dosing of all study medications was immediately ended in all subjects and the study was discontinued. After drug discontinuation, liver function tests in all affected subjects began to return to normal, clinical symptoms abated, and no deaths from this clinical study have been reported.
Roche now advises prescribers that rifampin should not be administered to patients also receiving saquinavir/ritonavir as part of combination antiretroviral therapy for HIV infection. Appropriate changes will be made to the package insert as soon as possible.