Anti-infective drug use and the risk of severe hepatic injury requiring hospitalization

Objectives: To compare the risk of severe hepatic injury requiring hospitalization among telithromycin users with users of other anti-infective agents with similar indications.

Methods: This was a retrospective cohort study using the PHARMetrics Integral Outcomes Database which contains medical and pharmacy insurance claims from managed care organizations across the United States. Patients who had had exposure to telithromycin, amoxicillin-clavulanic acid (Amox-clav), clarithromycin, and moxifloxacin between July 2004 and December 2005, and were 18 years of age or older with at least 1 year of claims history prior to dispensing were eligible for the study. The risk of severe hepatic injury requiring hospitalization following use of any of the above anti-infective agents was calculated. Risk ratios were estimated using the generalized estimating equations (GEE) method.

Results: During the study period, there were 124,413, 93,871, 202,456, and 111,336 eligible patients for telithromycin, Amox-clav, clarithromycin, and moxifloxacin cohorts respectively. The crude risk estimates of severe hepatic injury requiring hospitalization were 8.01 (95% CI 3.28, 12.75), 5.83 (95% CI 1.17, 10.50), 11.65 (95% CI 7.17, 16.13), and 16.93 (95% CI 9.69, 24.16) cases per 100,000 prescriptions for respective drug cohorts. The adjusted risk ratios of severe hepatic injury using Amox-clav as the reference group were 1.44 (95% CI 0.53, 3.89), 1.95 (95% CI 0.80, 4.73), and 2.58 (95% CI 1.04, 6.43) for telithromycin, clarithromycin, and moxifloxacin cohorts, respectively.

Conclusions: Risk of severe hepatic injury requiring hospitalization following telithromycin use is within the range of other antibiotics used for similar indications except moxifloxacin.