Perez GS, Garcia Rodriguez LA. The increased risk of hospitalizations for acute liver injury in a population with exposure to multiple drugs. Epidemiology. 1993 Nov 1;4(6):496-501.

We conducted a nested case-control study to estimate and compare the relative risks for hospitalizations for newly diagnosed acute liver injury associated with the use of non-steroidal antiinflammatory drugs (NSAIDs) and other hepatotoxic drugs and their interaction. The source population comprised 228,392 members of the Saskatchewan Health Plan from 1982 to 1986. We used hospital records and the databases of the Department of Health. Thirty-four cases with confirmed liver injury were hospitalized. We randomly selected 500 controls from the source population. Crude risks ranged from 1 case per 100,000 prescriptions in current users of methyldopa, ampicillin, or NSAIDs to 14 cases per 100,000 prescriptions in current users of erythromycin estolate. The age-adjusted odds ratios for current users of NSAIDs was 1.8 [95% confidence interval (CI) = 0.8-3.7] and for other hepatotoxic drugs 5.9 (95% CI = 2.8-12.4). The adjusted relative excess risk due to the interaction between current exposure to both categories of drugs was 3.6, accounting for 31% of the cases of acute liver injury among those with exposure to both types of drugs. We conclude that the risk of hospitalization for acute noninfectious liver injury is different among users of various individual potentially hepatotoxic drugs. Concomitant current exposure to two or more drugs increases this risk above what would merely be expected from the sum of the individual risks.

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