Drug-induced liver injury incidence

The incidence of drug-induced liver injury with rosiglitazone has been calculated at 0.02% for alanine transaminase activity 10 times the upper end of the reference range and 0.001% for jaundice (120). The above case report is unusual because, although liver damage is rare, hepatic necrosis occurs more commonly than cholestatic hepatitis. 

Meier, Y., et al., Incidence of drug-induced liver injury in medical inpatients. EurJ Clin Pharmacol, 2005. 61(2) p. 135 3. 

Hepatitis and jaundice caused by the combination of amoxicillin and clavulanic acid were first identified in 1988. The combination of the two drugs is associated with a higher incidence of liver injury than the administration of amoxicillin alone. The risk of this drug-induced liver injury, mostly cholestatic in nature, increases with age and by about a factor of 3 after 2 or more consecutive courses of drug. 

Hepatitis is an inflammation of the liver and is usually viral in origin however, certain chemicals, usually drugs, can induce a hepatitis that closely resembles that produced by viral infections (Table 14.1). This type of liver injury is not usually demonstrable in laboratory animals and is often manifest only in susceptible individuals. Fortunately, the incidence of this type of disease is very low. 

The relative contributions of amoxicillin and clavula-nate to co-amoxiclav-induced hepatotoxicity are incompletely understood. In patients with co-amoxiclav hepatotoxicity, previous use of amoxicillin and rechallenge with amoxicillin were both uneventful, pointing to clavulanic acid as the more likely culprit (16). In a report from the UK, the incidence of liver injury with amoxicillin alone was 0.3 per 10000 prescriptions versus 1.7 with co-amoxiclav (32). The risk increased after multiple use and with increasing age to 1 per 1000 prescriptions of co-amoxiclav. The main message is that the combination should be used with caution in elderly patients. A patient who has had documented hepatotoxicity related to co-amoxiclav should be well informed about this adverse drug reaction and any future use should be prohibited. 

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