Rifapentine: Its role in the treatment of tuberculosis

OBJECTIVE: TO review the pharmacokinetics, efficacy, adverse effects, and c ost of the newest antitubercular drug, rifapentine. DATA SOURCES: A MEDLINE search using key terms such as rifapentine, rifampi n, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted fo r the time period 1966-November 1998. STUDY SELECTION: Animal data were used for basic information and human stud ies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies asses sing the pharmacokinetics of rifapentine. Background articles on the pathop hysiology of tuberculosis and cost of care and noncontrolled studies assess ing drug interactions were also included. DATA SYNTHESIS: Compared with an oral solution, the relative bioavailabilit y of rifapentine is 70% following oral administration of tablets. Food incr eased bioavailability by 55%. Rifapentine accumulated significantly in huma n macrophages and its elimination half-life was longer than that of rifampi n. Comparative studies of rifapentine and rifampin in humans during intensi ve- and continuation-phase treatment of tuberculosis suggest that at curren tly accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse ev ents of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not stat istically significant. If only drug costs were evaluated during the six-mon th treatment of tuberculosis, rifapentine is more expensive than rifampin. CONCLUSIONS: Rifapentine can be administered twice weekly during the intens ive phase of tuberculosis treatment and then once weekly during the continu ation phase of treatment. This may improve patient adherence over some othe r treatments and possibly reduce costs of treatment by preventing developme nt of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar ra te as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifa mpin, although few drug interaction studies have been done with rifapentine . Its efficacy at the currently approved dosage of 600 mg may be slightly l ower than that of rifampin. Studies are needed to determine if equal or gre ater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are need ed to evaluate costs of relapse and failure in patients receiving these age nts.