Once-weekly
rifapentine 600 mg plus
isoniazid (INH) during the continuation phase treatment of
tuberculosis is associated with a relapse rate higher than that of twice-weekly
rifampin plus INH. The safety and tolerability of higher
rifapentine doses need to be determined. We conducted a prospective, randomized, double-blind trial of
rifapentine at three doses (600, 900, and 1,200 mg) plus INH 15 mg/kg once weekly in the continuation phase treatment of culture-positive
tuberculosis in 150 human immunodeficiency virus-seronegative adults. Outcome measures were discontinuation of
therapy for any reason and adverse events on
therapy. Treatment was discontinued in 3 of 52 (6%), 2 of 51 (4%), and 3 of 47 (6%) in the
rifapentine 600-, 900-, and 1,200-mg treatment arms, respectively. Only one discontinuation, in the
rifapentine 1,200-mg arm, was due to an adverse event possibly associated with study
therapy. There was a trend toward more adverse events, possibly associated with study
therapy, in the highest-dose arms (p = 0.051).
Rifapentine 900-mg, once-weekly dosing appears to be safe and well tolerated and is being evaluated in Phase III efficacy trials of treatment of
latent tuberculosis. Further evaluation of the safety and tolerability of
rifapentine 1,200 mg is warranted.