Lung TB: Higher dose of rifampicin safe, can boost recurrence-free survival, says ICMR study

New Delhi: A higher dose of rifampicin -- a bactericidal antibiotic used primarily to treat tuberculosis (TB)-may be safe, and its use can potentially lead to recurrence-free survival in patients with pulmonary TB, according to a recent study by the Indian Council of Medical Research (ICMR).

TB is curable but still remains the most common cause of death due to infectious diseases, with an estimated 1.3 million deaths globally in 2022. Rifamycins are a crucial drug group in the anti-TB regimen, which sterilise the lesions and aid in recurrence-free cure.

Currently, rifampicin is administered at 10 mg/kg for six months to all patients with pulmonary TB.

The team reviewed the available evidence from published clinical trials to determine whether higher doses of rifampicin (more than 15 mg/kg) are more efficacious and safer.

“Compared to standard dose, higher doses of rifampicin were found to lead to early sputum conversion in eight weeks and thus faster TB bacteria clearance,” said corresponding author Dr Leeberk Raja Inbaraj, Department of Clinical Research, ICMR- National Institute for Research in Tuberculosis, Chennai.

Early sputum conversion is a valuable tool widely used as a surrogate marker for treatment response and those who are at risk for relapse in pulmonary TB.

“The ability of high-dose rifampicin to achieve early sputum conversion and eliminate the persistent bacteria that cause relapse could potentially lead to recurrence-free survival. Early bacterial clearance is also of public health importance as this could potentially reduce disease transmission in the community,” the researchers said.

Notably, the study showed 20-30mg/kg rifampicin as the best balance.

“This dose range showed better sputum conversion without a significant increase in serious side effects and may be considered in TB treatment,” revealed the study, published in the Indian Journal of Medical Research (IJMR).

On the other hand, doses above 30 mg/kg, although beneficial, came with severe side effects such as serious liver damage (hepatotoxicity) and adverse drug reactions (ADR), leading to treatment discontinuation.

The study showed no reduction in death or treatment failure in people with more than 15 mg/kg doses of rifampicin.

“High doses did not reduce mortality or treatment failure at 6 months compared to standard treatment,” the team said.

“This dose could be administered with close monitoring of adverse events and hepatotoxicity. There is an urgent need for adequately powered trials that assess long-term treatment outcomes, including recurrence,” they added.