Safety of Triple-Dose Rifampin in Tuberculosis Treatment: A Systematic Review and Meta-Analysis

Area of Science:

• Tuberculosis Treatment
• Pharmacovigilance
• Systematic Review and Meta-Analysis

Background:

• Growing interest in high-dose rifampin for tuberculosis treatment.
• Recent studies suggest potential safety concerns with triple-dose rifampin (TDR; ≥30 mg/kg/day).

Purpose of the Study:

• To systematically review and update evidence on the safety and efficacy of TDR compared to standard-dose rifampin (SDR) in tuberculosis treatment.

Main Methods:

• Systematic search of multiple databases (Embase, MEDLINE, Cochrane) and clinicaltrials.gov for randomized-controlled trials (RCTs) up to February 2024.
• Meta-analysis of pooled incidence rate ratio (IRR) for severe adverse events (SevAE) and relative risk (RR) for death.
• Assessment of heterogeneity (I2) and bias (Cochrane Risk of Bias 2).

Main Results:

• 17 RCTs with 2313 SDR, 2238 double-dose rifampin (DDR), and 1199 TDR participants were included.
• TDR was associated with a significant increase in SevAE compared to SDR (IRR 1.48), primarily driven by hepatic events (IRR 1.96).
• No significant difference in the risk of death was observed between TDR and SDR groups (RR 1.19).

Conclusions:

• Regimens utilizing TDR are linked to an increased incidence of severe adverse events in human tuberculosis treatment.
• The safety profile of TDR warrants careful consideration due to elevated risks, particularly hepatic events.