Liver reactions to oral low-dose tetracyclines

We report on a case of severe liver reaction associated with doxycycline in a previously healthy subject. Furthermore, we estimate the incidence of oral low-dose tetracycline-related liver reactions in relation to sales figures in Sweden and study the clinical and biochemical features of low-dose tetracycline-associated liver injury, on the basis of reports to SADRAC (Swedish Adverse Drug Reactions Advisory Committee) and on the reports in the literature.

All liver reactions reported to SADRAC from 1965 to 1995 were surveyed, and articles on liver reactions resulting from tetracycline published during the period 1966-95 were reviewed.

During this 30-year period, 23 liver reactions with a suspected casual relationship to oral, low-dose tetracycline derivatives were reported to SADRAC. A causal relationship was considered likely in 3 and possible in 8 cases, giving an incidence of roughly 1 in 18 million DDD (defined daily doses). No deaths were observed from these liver reactions, and liver enzyme activities normalized in all cases without any serious clinical consequences. A total of three cases of reported tetracycline liver damage were found in the literature. Of these, two were classified as having a likely relationship, and in one a causal relationship was not determinable because of other concomitant drug administration. The liver injury was designated as cholestatic, hepatocellular, and mixed, with similar frequencies.

Low-dose, oral tetracyclines constitute a likely cause of acute liver damage with a variable biochemical profile. Such reactions are probably very rare.