TB: Is a Higher Dose of Rifampin Safe?
Higher daily doses of rifampin appeared to be safe and effective for the treatment of tuberculosis (TB) in a new study, indicating that a treatment period of less than 6 months may be on the horizon.1
In addition to the potential to shorten the standard treatment time for TB, these findings are especially encouraging due to the low cost, potent sterilizing effect, and worldwide accessibility of rifampin capsules.2
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For their study, Gustavo E. Velásquez, MD, MPH, associate physician in the Division of Infectious Diseases at Brigham and Women's Hospital in Boston, Massachusetts, and colleagues evaluated 180 adults with new, drug-susceptible TB in Lima, Peru.
For the first 8 weeks of intensive therapy, participants were randomly assigned to receive either a standard dose of 10 mg/kg/day of rifampin or higher doses of 15 mg/kg/day or 20 mg/kg/day in combination with standard doses of isonaniazid, pyrazinamide, and ethambutol—other first line drugs for TB.
Subsequently, all participants were treated with standard doses of rifampin and isoniazid over throughout 4 months of continuation therapy.
Following adjustment for age, sex, and extent of disease, results of the study showed that each additional 5 mg/kg/day increase in rifampin was associated with a higher elimination rate of TB bacteria from sputum, as well as plasma.
Notably, higher doses of rifampin were not found to be associated with more grade 2 or higher rifampin-associated adverse events. Although liver toxicity and flu-like syndrome are commonly reported with rifampin use, the researchers did not observe any occurrences of flu-like syndrome in this cohort.
However, the researchers noted that their study was not able to determine whether the rates of culture conversion differed between the 3 treatment arms.
“The difference was too modest at the tested doses for successful treatment shortening,” said Dr Velásquez in a press release.2 “However, these results, trial taken together with other recently published reports, support efforts to increase doses of rifampin to 35 mg/kg/day and possibly higher until the maximum tolerable dose is identified.”
—Christina Vogt
Reference:
1. Velásquez 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]. J Respir Crit Care Med. http://www.thoracic.org/about/newsroom/press-releases/resources/rifampin-and-tb.pdf
2. Higher doses of rifampin appear more effective in fighting TB without increasing risk of adverse events [press release]. American Thoracic Society. June 29, 2018. Accessed on June 29, 2018.