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1 Universidad Complutense de Madrid Madrid 2 Service de cardiologie 3 Service de cardiologie et maladies vasculaires 4 LTSI - Laboratoire Traitement du Signal et de l-Image 5 CIC-IT Rennes

Abstract : Purpose The therapeutic index TI is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI NTIDs have a narrow window between their effective doses and those at which they produce adverse toxic effects. Generic drugs may be substituted for brand-name drugs provided that they meet the recommended bioequivalence BE limits. However, an appropriate range of BE for NTIDs is essential to define due to the potential for ineffectiveness or adverse events. Flecainide is an an-tiarrhythmic agent that has the potential to be considered an NTID. This review aims to evaluate the literature surrounding guidelines on generic substitution for NTIDs and to evaluate the evidence for flecainide to be considered an NTID. Methods A review of recommendations from various regulatory authorities regarding BE and NTIDs, and publications regarding the NTID characteristics of flecainide, was carried out. Results Regulatory authorities generally recommend reduced BE limits for NTIDs. Some, but not all, regulatory authorities specify flecainide as an NTID. The literature review demonstrated that flecainide displays NTID characteristics including a steep drug dose–response relationship for safety and efficacy , a need for therapeutic drug monitoring of pharmacokinetic PK or pharmacodynamics measures and intra-subject variability in its PK properties. Conclusions There is much evidence for flecainide to be considered an NTID based on both preclinical and clinical data. A clear understanding of the potential of proarrhythmic effects or lack of efficacy, careful patient selection and regular monitoring are essential for the safe and rational administration of flecainide.

Keywords : Bioequivalence Antiarrhythmic drugs Flecainide Narrow therapeutic index Safety Generic drugs





Autor: Juan Tamargo - Jean-Yves Le Heuzey - Phillipe Mabo -

Fuente: https://hal.archives-ouvertes.fr/



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