TB Drug Interaction and Absorption
E.II Given the expected drug interactions that would result in markedly decreased serum levels of antiretroviral agents, and given the overlapping toxicities, the coadministration of rifampin with any of the protease inhibitors or with NNRTIs, as well as the coadministration of rifabutin with ritonavir, hard-gel saquinavir (Invirase), or delavirdine, is contraindicated.

A.II The potent effect of rifampin as a CYP450 inducer, which lowers the serum concentration of protease inhibitors and NNRTIs, is expected to continue up to at least 2 weeks following the discontinuation of rifampin. Therefore, to diminish the likelihood of adverse effects on drug metabolism, clinicians should plan the start of therapy with protease inhibitors or NNRTIs at least 2 weeks after the date of the last dose of rifampin.

A.II Rifabutin is a less potent CYP450 inducer than rifampin and thus can be used (with adjustments in dosages) concurrently with the NNRTIs nevirapine or efavirenz or with certain protease inhibitors (e.g., indinavir, nelfinavir, and possibly soft-gel saquinavir Fortovase{} and amprenavir). No rating Indinavir serum concentrations are decreased by rifabutin-related induction of the hepatic cytochrome P450; therefore, when indinavir is used incombination with rifabutin, the dose of indinavir usually is increased from 800 mg every 8 hours to 1,200 mg every 8 hours. No rating Nelfinavir serum concentrations are also decreased when nelfinavir is used in combination with rifabutin (Table 1A of Appendix); however, the resultant metabolite of nelfinavir is known to be active against HIV. Nevertheless, some experts suggest increasing the dose of nelfinavir from 750 mg three times per day to 1,000 mg three times per day when used in combination with rifabutin. No rating Experts do not know whether dose-modifications are needed for soft-gel saquinavir (Fortovase ), amprenavir, nevirapine, or efavirenz if these agents are used in combination with rifabutin. No rating Many other medications commonly used by patients with HIV infection have drug interactions with the rifamycins (rifampin or rifabutin) of sufficient magnitude to require interventions such as dose adjustments or use of alternative therapies. Some examples of these drugs are hormonal contraceptives, dapsone, ketoconazole, fluconazole, itraconazole, narcotics (including methadone), anticoagulants, corticosteroids, cardiac glycosides, hypoglycemics (sulfonylureas), diazepam, beta-blockers, anticonvulsants, and theophylline. No rating Malabsorption of antituberculosis drugs has been demonstrated in some patients with HIV infection, and in some cases, it has been associated with TB treatment failures and the selection of drug-resistant M. tuberculosis bacilli (141-145). Therapeutic drug monitoring has been advocated by some experts as an adjunct in the management of HIV-related TB (146). This approach might be useful when evaluating patients with TB treatment failure or relapse and in the treatment of multidrug-resistant (MDR) TB. However, the role of therapeutic drug monitoring in the routine management of TB among HIV-infected patients has not been established and is not presently recommended.

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