Higher Rifampin Dose Effective and Safe in Tuberculosis

Higher daily dosages of rifampin are as effective as the standard of care for tuberculosis without increasing adverse effects, according to a recent study published in the American Journal of Respiratory Critical Care Medicine.

Researchers of this phase 2 study examined the efficacy and safety of rifampin when used at dosages of 10, 15, or 20 mg/kg/d. Patients who tested positive for tuberculosis (N=180) were randomly assigned to 1 of 3 treatment groups and then monitored for reductions in Mycobacterium tuberculosis and toxicities.

Both 15 mg and 20 mg doses showed a rapid decline in bacteria. For each 5 mg/kg increase in rifampin dose in the modified intention-to-treat population, the researchers estimated a difference of –0.011 log₁₀ colony forming units/mL/d (95% CI, –0.025 to –0.002 log₁₀ colony forming units/mL/d) in elimination rate between treatment groups (P =.230). Meanwhile, in the per-protocol population, the difference was even higher at –0.022 log₁₀ colony forming units/mL/d (95% CI, –0.046 to –0.002 log₁₀ colony forming units/mL/d; P =.022).

Similar grade 2 adverse event frequencies were also seen across the treatment groups (43.3%, 51.7%, and 38.3% of participants in the 10, 15, and 20 mg/kg/d groups, respectively). The rate of bacterial sterilization was proportionally related to the increase in doses of rifampin. The most common adverse events were hepatic, gastrointestinal, musculoskeletal, and respiratory related. 

The effects of higher doses of rifampin need to be further evaluated. In this study, the 20 mg/kg/d resulted in only a slightly higher total dose than the 15 mg/kg/d. This was due to the average weight of patients in the 20 mg group being lower than those in the15 mg group. The researchers also did not find a significant difference in the efficacy of the two higher doses, and it was hypothesized that there would be a greater effect if the dosage was increased.

Reference

Veláquez GE, Brooks MB, Coit JM, et al. Efficacy and safety of high-dose rifampin in pulmonary tuberculosis: a randomized controlled trial [published online June 29, 2018]. Am J Respir Crit Care Med. doi: 10.1164/rccm.201712-2524OC