ACUTE-LIVER-DISEASE ASSOCIATED WITH ERYTHROMYCINS, SULFONAMIDES, AND TETRACYCLINES

Objective: To determine whether erythromycins, sulfonamides, and tetra cyclines are associated with an increased risk for acute hepatitis. De sign: Case-control study. Setting: Medicaid billing data from Michigan and Florida between 1980 and 1987. Patients: The 107 cases included p atients hospitalized with acute symptomatic hepatitis without an ident ifiable cause of liver disease noted in the medical record. Four contr ols per case were randomly selected and were matched for age, sex, and state. Results: Five cases (4.7%) and four controls (0.9%) were expos ed to erythromycins, yielding an odds ratio of 5.2 (95% CI, 1.1 to 26. 6). No case or control was exposed to erythromycin estolate. Eight cas es (7.5%) and three controls (0.7%) were exposed to oral sultonamides, yielding an odds ratio of 11.4 (CI, 2.7 to 67.8). All (except one con trol) had received trimethoprimsulfamethoxazole. Five cases (4.7%) and four controls (0.9%) were exposed to tetracyclines, yielding an odds ratio of 5.2 (CI, 1.4 to 19.7). The results did not change substantive ly for erythromycin or sulfonamides after adjustment using multiple lo gistic regression for age, sex, state, and use of other hepatotoxic dr ugs. With tetracyclines, however, the odds ratio decreased to 3.6 (CI, 0.9 to 14.3). Associations were also seen with isoniazid (P = 0.008) and rifampicin (P = 0.04). The number of patients developing acute sym ptomatic liver disease resulting in hospitalization for each million p atients treated with a 10-day course of erythromycin was 2.28 cases; f or sulfonamides, this figure was 4.8 cases; and for tetracycline, the figure was 1.56 cases. Conclusion: Erythromycin, sulfonamides, and tet racyclines are associated with acute symptomatic hepatitis resulting i n hospitalization. Given the widespread use of these drugs, they will be among the more common drugs associated with hepatitis.