Exposure to potential drug-antimicrobial agent interactions in primary health care

Background/Aim. Drug-drug interactions involving antimicrobials present important and often unrecognized complications of pharmacotherapy which can be prevented. The aim of the present study was to identify the frequency and type of potential drug-antimicrobial agent interactions among outpatients and to define recommendations for their management. Methods. Crosssectional prescription database study was conducted. The analysis randomly included 823 patients who visited Health Center Novi Sad over 1-month period (November 1–30, 2011) and had prescribed ≥ 2 drugs where at least one drug was antimicrobial agent for systemic use. All interacting drug combinations involving antimicrobials were identified according to Drug Interaction Facts. Additionally, based on the compendium, potential interactions were classified into categories: pharmacological mechanisms, potential clinical outcomes and management advice. Results. Overall, 88 potential clinically significant drug-antimicrobial agent interactions were identified among 69 (8.4%) exposed outpatients [the mean age 61.7 years (SD ± 15.4); the mean number of prescribed drugs 7.5 (SD ± 2.9); 56.5% females]. The most common identified potential interacting pairs were benzodiazepines undergoing oxidative metabolism and clarithromycin or erythromycin, and aminophylline and ciprofloxacin. In 83.0% of all cases underlying mechanism was pharmacokinetic involving primary inhibition of metabolic pathways mediated by CYP3A4 and CYP1A2 isoenzymes. Excessive sedation (22.7%), cardiotoxicity (20.5%), miscellaneous aminophylline adverse effects (13.6%), and bleeding (10.2%) were the most frequently implicated potential clinical outcomes. Risk for adverse interactions could be managed by close monitoring of simultaneous administration of drugs (37.5%), different risk-modifyng strategies (31.8%), and avoiding combinations (30.7%). Conclusion. Among outpatients, there was common potential for clinically significant interactions involving antimicrobials. Information based on the results of the present study could be integrated in existing computerized physician order entry system in the Health Center as a form of clinical support