Drug associated hepatic reactions in New Zealand: 21 years experience.

Aims: To review spontaneous reports of drug-associated adverse hepatic reactions.

Methods: Reports of drug-associated adverse hepatic reactions received by the New Zealand Centre for Adverse Reactions Monitoring over the 21 year period January 1974 to December 1994 were reviewed. Subdivision into three 7 year periods was undertaken to compare patterns.

Results: Of a total of 22,455 adverse medicine reaction (AMR) reports there were 943 reports of liver injury (4.2%). Two hundred and five drugs were associated with hepatic reactions. The top 20 drugs accounted for 57% of all liver reactions. Fifty-seven percent were reported in females. Hepatotoxicity was most commonly reported among patients 50-80 years old. Liver reactions were associated with a 3.3% mortality, but were responsible for 7.4% of all fatal occurrences. There was a steady increase in the number of reports over the 21 years. Although the largest number of reports of liver injury were received between 1988 and 1994, mortality was lowest during this period. There were substantial differences in the medicines associated with hepatic reactions during each of the three periods, although erythromycin was the commonest cause throughout. Erythromycin was associated with two deaths. Halothane and perhexilene were the most frequent cause of death and were two of the most important causes of liver injury during the first and second periods. Diclofenac, Augmentin and flucloxacillin were important causes of hepatotoxicity during period 3 but were not associated with a fatal outcome.

Conclusion: Hepatic reactions accounted for 4.2% of all adverse medicine reactions and 7.4% of all fatal occurrences. The top 20 drugs were responsible for 57% of all liver reactions. Despite a steady increase in the number of reports during the 21 years, mortality was lowest during the last 7 years. Differences in the medicines causing liver injury during the three periods influenced the number of fatalities. Erythromycin was the most commonly reported cause of hepatic reactions but was usually associated with a favourable outcome. There were no reported deaths with diclofenac, Augmentin or flucloxacillin.