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AIMS The objective of this study was to estimate the risk of acute liver injury associated with individual acid-suppressing drugs and assess the role of dose and duration of treatment. METHODS We used a nested case-control study design within a cohort of over 100,000 users of cimetidine, famotidine, omeprazole and ranitidine. The primary source of information was the General Practitioners Research Database. We identified 108,981 persons aged 20-74 years who received at least one prescription for cimetidine, famotidine, omeprazole, or ranitidine during 1990-93, and we ascertained the first occurrence of clinically acute liver injury referred to a specialist or admitted to a hospital. RESULTS After review of medical records, 33 patients were considered eligible cases of idiopathic acute liver injury with no fatal cases. The type of liver injury was hepatocellular in almost half of the cases, and 80% of all cases presented with jaundice. Twelve cases occurred among current users of cimetidine, five among ranitidine users and one in an omeprazole user. The absolute risk of acute liver injury associated with cimetidine was estimated to be slightly greater than one per 5000 users of cimetidine. The adjusted relative risk (RRs) and 95% CI of developing acute liver injury associated with current use of cimetidine compared to non-use was 5.5 (1.9-15.9), with omeprazole 2.1 (0.2-19.2) and with ranitidine 1.7 (0.5-5.8). In the absence of concomitant use of other hepatotoxic drugs, the RR with cimetidine was 14.4 (2.9-73.7). Among users of cimetidine, the risk was especially high in the first 2 months of starting therapy (RR: 11.3, 3.7-35.1) and at daily doses of 800 mg or greater (RR: 8.8, 3.0-26.0). CONCLUSIONS Cimetidine was the individual anti-ulcer drug with the highest risk of developing symptomatic acute liver disease. Further data are required to confirm this finding. Our study indicates that there is a dose relationship and a short latent period between cimetidine treatment and acute liver injury.

Purpose: Recently, the Blue Mountains Eye Study reported an association between the use of topical timolol and cardiovascular mortality (Lee et al. Ophthalmology 2006). The purpose of the present study was to confirm or falsify this clinically very important finding, using data from the population-based Rotterdam Study. Methods: 6971 participants of the Rotterdam Study, a longitudinal population based study of all residents aged 55 years and older from a district of Rotterdam, The Netherlands, were followed from 1991 onwards. Medication use and morbidity were recorded continuously during follow-up. For the current analysis, baseline use of topical beta-blockers and systemic cardiovascular medication as well as baseline cardiovascular morbidity were used, aiming to follow the design of the Blue Mountains Eye Study as close as possible. Cause of death was registered up to 1-1-2005. Data were analysed using Cox regression; Hazard ratios of topical beta-blocker use were adjusted for age, sex, cardiovascular morbidity and use of systemic cardiovascular medication. Results: Mean age at baseline was 69 years (SD 9 years); 146 participants were using topical beta-blockers at baseline. 2726 participants died during follow-up (all cause mortality 40.1%), 611 (9.0%) had a cardiovascular cause of death. Hazard ratio of topical beta-blocker use was 0.80 (95% confidence interval 0.63-1.02; P=0.07) for all cause mortality and 0.78 (0.46-1.29; P=0.32) for cardiovascular mortality. Conclusions: In our data, the use of topical beta-blockers at baseline was not associated with either all cause mortality or cardiovascular mortality during follow-up.

BACKGROUND: Anaphylactic reactions to cotrimoxazole are often ascribed to the sulphamethoxazole component of this antibacterial drug. OBJECTIVE: To determine whether the trimethoprim component can be the cause of an anaphylactic reaction. METHODS: An analysis was made of reports on anaphylaxis attributed to trimethoprim, as notified to the Drug Safety Unit of the Dutch Inspectorate for Health Care. RESULTS: In the period between September 1981 and November 1995, 13 such reports were received. Nine were classified as probable anaphylaxis. Of these, the causal relationship between exposure to trimethoprim and anaphylaxis was classified as definite in three reports, and as probable in the other six. The remaining four reports were classified as possible anaphylaxis. In one of these, the causal relationship was classified as definite, and in three as probable. CONCLUSION: Although anaphylaxis due to trimethoprim seems to be rare, it may be more common than previously thought. Apparently, anaphylaxis to cotrimoxazole is not always caused by sulphamethoxazole.