A pharmacovigilance study of the association between tetracyclines and hepatotoxicity based on Food and Drug Administration adverse event reporting system data.

Background While tetracycline antibiotics are commonly prescribed in practice, the risk of drug-induced liver injury (DILI) remains controversial. Aim To evaluate the association of DILI with tetracycline antibiotics. Method All DILI cases of tetracycline antibiotics as primary suspected drugs were extracted from the US Food and Drug Administration adverse event reporting system (FAERS). The outcomes included severe DILI, hepatocellular injury, cholestatic injury, and liver failure. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results A total of 1,435 liver injury cases associated with tetracycline antibiotics were identified. The DILI signal was detected in tigecycline, minocycline, and doxycycline. The RORs and the 95% confidence intervals (95% CI) of tigecycline, minocycline, and doxycycline were (ROR 5.85, 95% CI 4.96-6.91), (ROR 6.4, 95% CI 5.76-7.11), and (ROR 2.07, 95% CI 1.86-2.31), respectively. Compared to minocycline (ROR 5.5, 95% CI 4.94-6.12; IC 2.35, 95% CI 1.98-2.68) and doxycycline (ROR 1.91, 95% CI 1.71-2.12; IC 0.91, 95% CI 0.55-1.26), tigecycline showed a stronger association with hepatocellular injury (ROR 7.11, 95% CI 6.13-8.23; IC 2.68, 95% CI 2.16-3.13). Tigecycline also showed a stronger association with cholestatic injury (ROR 12.16, 95% CI 10.13-14.61; IC 3.51, 95% CI 2.79-4) than minocycline (ROR 3.23, 95% CI 2.59-4.04; IC 1.67, 95% CI 0.9-2.37) or doxycycline (ROR 2.86, 95% CI 2.47-3.31; IC 1.5, 95% CI 1-1.97). Tigecycline (ROR 6.56, 95% CI 4.57-9.41; IC 2.69, 95% CI 1.28-3.64) and minocycline (ROR 4.22, 95% CI 3.14-5.66; IC 2.06, 95% CI 1-2.93) showed a significant association with liver failure. Conclusion The data mining of FAERS suggested an association between DILI and tigecycline, minocycline, and doxycycline.