The impact of rifampin drug interactions on tuberculosis preventive treatment completion and safety

BACKGROUND Rifamycin TB preventive treatment (TPT) is critical to TB elimination. However, clinicians may be reluctant to recommend it over concerns related to drug-drug interactions (DDI). In this secondary analysis of data from the 2R² randomised clinical trial (comparing standard dose rifampin to high-dose rifampin for TPT), we investigate if participants taking medications with potential rifampin DDI had similar TPT completion, safety, and follow-up visits compared to those without. METHODS Data on concomitant medications, adverse events, treatment completion, and follow-up visits were compared between participants with and without potential rifampin DDI. Analyses were conducted with R, reporting risk difference (RD) using g-computation with logistic regression. RESULTS 282 of 1,368 participants (21%) were taking essential medications with potential rifampin DDI. There was no RD in TPT completion (RD 0.04 [95% confidence interval (CI): -0.02; 0.09]) or adverse events (RD 0.02 [95% CI: -0.01; 0.06]) between participants with and without these medications. Individuals talking medications with potential DDI had a higher percentage of two or more unscheduled visits (12%) compared to those not taking them (5%) (P = 0.0001). CONCLUSION In participants taking medications with potential rifampin DDI, rifampin TPT can be used safely without impacting completion rates. However, additional follow-up visits should be anticipated. .