Objective The aim was to develop a drug-drug interaction database (SFINX) to be integrated into decision support systems or to be used in website solutions for clinical evaluation of interactions. Methods Key elements such as substance properties and names, drug formulations, text structures and references were defined before development of the database. Standard operating procedures for literature searches, text writing rules and a classification system for clinical relevance and documentation level were determined. ATC codes, CAS numbers and country-specific codes for substances were identified and quality assured to ensure safe integration of SFINX into other data systems. Much effort was put into giving short and practical advice regarding clinically relevant drug-drug interactions.Results SFINX includes over 8,000 interaction pairs and is integrated into Swedish and Finnish computerised decision support systems. Over 31,000 physicians and pharmacists are receiving interaction alerts through SFINX. User feedback is collected for continuous improvement of the content. Conclusion SFINX is a potentially valuable tool delivering instant information on drug interactions during prescribing and dispensing.
We conclude that co-medication in warfarin-treated in-patients is common and should be carefully evaluated to decrease the bleeding risk associated with warfarin therapy.
Coadministration of drugs that potentially result in inhibition of prodrug activation present a common and unrecognized source of irrational prescribing.
Abstract. Tirkkonen T, Heikkilä P, Huupponen R, Laine K (University of Turku; Turku University Hospital; and StatFinn Ltd; Turku, Finland). Potential CYP2C9-mediated drug-drug interactions in hospitalized type 2 diabetes mellitus patients treated with the sulphonylureas glibenclamide, glimepiride or glipizide. J Intern Med 2010; 268: 359-366.Objectives. Sulphonylureas are widely used in the treatment of type 2 diabetes mellitus (T2DM). Based on laboratory findings, we determined the clinical significance of potential CYP2C9-mediated drug-drug interactions in hospitalized patients receiving glibenclamide, glimepiride or glipizide, all of which are metabolized by CYP2C9, together with a CYP2C9 inhibitor.Design, setting and subjects. An observational pharmacoepidemiological database study was performed in a university hospital setting with 3884 patients with T2DM.Main outcome measures. Efficacy and safety of sulphonylurea therapy during the potential interaction (sulphonylurea treatment with a CYP2C9 inhibitor) vs. control periods (sulphonylurea treatment without a CYP2C9 inhibitor) were estimated using laboratory parameters.Results. Almost 20% of patients were exposed to a potential drug-drug interaction with a CYP2C9 inhibitor during sulphonylurea treatment. More than 75% of the potential interactions occurred with trimethoprim, metronidazole and fluconazole. When all sulphonylureas were pooled and adjusted for age, gender, ward and sulphonylurea dose, mean and maximum fasting plasma glucose concentrations as well as maximum values of glycosylated haemoglobin were significantly lower during the interaction periods compared with control periods, whereas mean and minimum activities of alanine amino transferase and gamma-glutamyl transferase were higher. The minimum fasting plasma glucose values were more often below the target range in patients with potential interactions. The sulphonylurea dose did not differ significantly between patients who were or were not concomitantly treated with a potentially interacting drug.Conclusions. Concomitant use of a CYP2C9 inhibitor results in exaggerated pharmacodynamic effects of sulphonylureas and increases the risk of hypoglycaemia in T2DM patients receiving glibenclamide, glimepiride or glipizide.
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