Liver Reactions to Oral Low-Dose Tetracyclines

Abstract

Background: 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. Methods: 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. Results: During this 30-year period, 23 liver reactions with a suspected causal 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. Conclusions: Low-dose, oral tetracyclines constitute a likely cause of acute liver damage with a variable biochemical profile. Such reactions are probably very rare.

Key Words:

• Adverse drug reactions
• liver damage
• tetracyclines