Critical Drug Interactions With Agents Used for Prophylaxis and Treatment of Mycobacterium avium Complex Infections

Abstract

Drug interactions occur through drug-induced hepatic enzyme induction or inhibition, or alterations in drug absorption or renal elimination. Three gene families of the cytochrome P-450 enzyme system, CYP1, CYP2, and CYP3, and five cytochrome P-450 isozymes, CYP 1A2, 2C9, 2D6, 2E1, and 3A4, are involved with the most frequently recognized drug interactions for agents used in the treatment of HIV disease and its complications. Major interactions occur when clarithromycin and/or rifabutin, used for prophylaxis or treatment of Mycobacterium avium complex (MAC), are administered together or with the azoles, the antiretroviral protease inhibitors, or the nonnucleoside reverse transcriptase inhibitors. Clarithromycin is an inhibitor of the activity of CYP 3A4. Rifabutin is a moderately potent inducer of the activity of CYP 3A4. Although still under investigation, azithromycin does not appear to affect the CYP 3A system. Ritonavir is both an inhibitor and an inducer of the activity of CYP 3A4, depending on the metabolic pathway utilized by specific drugs. Indinavir appears to be a reversible and less potent inhibitor of CYP 3A4 than ritonavir. Nevirapine is an inducer of CYP 3A4. The metabolism of other drugs that utilize this isozyme metabolic pathway in particular may be adversely affected when given concomitantly with any of these drugs. It is important for clinicians to be aware of such drug interactions in order to avoid adverse outcomes when prescribing prophylaxis or treatment for disseminated MAC.