The prevalence of potential clinically significant drug interactions with angiotensin-converting enzyme inhibitors in Slovenia

M Pal1, B Leskošek2, P Ferk1. 1University of Maribor, Faculty of Medicine, Department of Pharmacology and Experimental Toxicology, 2000, Slovenia, 2University of Ljubljana, faculty of Medicine, Institute for Biostatistics and Medical Informatics, 1000, Slovenia

Objective: The aim of our study was to assess the prevalence of potential clinically significant drug interactions with angiotensin-converting enzyme (ACE) inhibitors among 296.558 Slovene patients, who received an ACE inhibitor at least once in 2010.

Design and methods: Potential clinically significant drug interactions with ACE inhibitors were identified by three sources: Stockley’s Drug Interactions book and two on-line databases, Lexi-Interact (payable) and Drug Interaction Checker at Drugs.Com (free access). Concerning ACE inhibitors, the major interactions from Drug Interaction Checker and the interactions of levels D and X from Lexi-Interact were selected to be investigated in our study. The data on drug consumption in Slovene patients who had received an ACE inhibitor at least once in 2010 were obtained from the Health Insurance Institute of Slovenia database of drugs dispensed by all Slovene community pharmacies. We identified 204 drug interacting pairs and counted all the cases when the pairs of drugs were dispensed to patients on the same day. Because of the large data quantity (number of prescriptions), the data was normalized and transformed to an SQL database (MySQL); afterwards, it was analyzed using our own software (written in Perl) designed for browsing, (SQL) querying and searching for drug interactions.

Results: In our study sample, which is representative of all regions of Slovenia, the prevalence of drug interactions with ACE inhibitors, dispensed on the same day, was relatively low. The numbers of cases and patients with a drug-drug interacting pair dispensed on the same day in 2010 are presented below (Table 1). The highest prevalence of drug interactions with ACE inhibitors was observed for allopurinol, heparin, potassium-sparing diuretics, potassium salts and tizanidine.

Table 1: Numbers of cases and patients with a drug-drug interacting pair dispensed on the same day in 2010

Conclusions: According to the results of our study, we emphasize the importance of monitoring potential drug interactions with ACE inhibitors especially for allopurinol, heparin, potassium-sparing diuretics, potassium salts and tizanidine. Fortunately, the majority of the interactions can be managed by clinical and laboratory monitoring of patients or by dosage adjustments of one or both agents. Additionally, our approach and the results may serve as a basis for future evaluation of the prevalence of clinically manifested drug interactions with ACE inhibitors and also for improving the ACE inhibitors prescribing in Slovenia and elsewhere in Europe.