1. J Antimicrob Chemother. 2011 Jul;66(7):1431-46. Epub 2011 May 17.

Hepatic safety of antibiotics used in primary care.

Andrade RJ, Tulkens PM.

Hepatology Unit, Gastroenterology Service, Virgen de la Victoria University
Hospital Department of Medicine, University of Málaga, Spain.

Antibiotics used by general practitioners frequently appear in adverse-event
reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse
reaction cannot be predicted from the drug's pharmacological profile or from
pre-clinical toxicology tests) and occur via an immunological reaction or in
response to the presence of hepatotoxic metabolites. With the exception of
trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude
incidence remains globally low but variable. Thus, amoxicillin/clavulanate and
co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates
that make them visible in general practice (cases are often isolated, may have a 
delayed onset, sometimes appear only after cessation of therapy and can produce
an array of hepatic lesions that mirror hepatobiliary disease, making causality
often difficult to establish). Conversely, hepatotoxic reactions related to
macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) 
are much rarer, and are identifiable only through large-scale studies or
worldwide pharmacovigilance reporting. For antibiotics specifically used for
tuberculosis, adverse effects range from asymptomatic increases in liver enzymes 
to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single 
out individual drugs, as treatment always entails associations. Patients at risk 
are mainly those with previous experience of hepatotoxic reaction to antibiotics,
the aged or those with impaired hepatic function in the absence of close
monitoring, making it important to carefully balance potential risks with
expected benefits in primary care. Pharmacogenetic testing using the new
genome-wide association studies approach holds promise for better understanding
the mechanism(s) underlying hepatotoxicity.

PMCID: PMC3112029
PMID: 21586591  [PubMed - in process]