Drug interactions common in patients with HIV infection and mycobacterium avium complex disease

Mycobacterium avium complex (MAC) disease, a relatively common opportunistic infection in patients with AIDS, is usually treated with a macrolide-based combination regimen. A macrolide or rifabutin has also been recommended for prevention of MAC infection. However, these drugs and many others used to treat HIV infection and related opportunistic infections interact with the cytochrome P450 (CYP) enzyme system. Thus, complex drug interactions can result when these agents are administered together. Coadministration of clarithromycin, fluconazole or itraconazole with rifabutin markedly increases plasma concentrations of rifabutin and has resulted in increased rifabutin toxicity. These combinations should be avoided if possible or administered under very close monitoring. Delavirdine and most protease inhibitors also substantially increase plasma concentrations of rifabutin, while plasma concentrations of the antiretroviral drugs are often markedly decreased. Efavirenz lowers plasma concentrations of rifabutin. Clarithromycin interacts with most of the drugs which interact with rifabutin. Fluconazole, delavirdine and most protease inhibitors increase clarithromycin plasma concentrations, while plasma concentrations of the antiretroviral drugs are generally increased. However, these interactions do not generally warrant dosage adjustment. Coadministration of clarithromycin with nevirapine or efavirenz lowers plasma concentrations of clarithromycin and these combinations are best avoided. Azithromycin has comparatively few interactions with antiretroviral agents or other drugs used to treat MAC.