İlaç etkileşimlerinin araştırlmasına yönelik EMA (Avrupa İlaç Ajansı) kılavuzu (İng)
New EMA guideline on the investigation of drug interactions
EMA has published a updated guideline on “Investigation of Drug Interactions.” Drug-drug interactions are a common problem during drug treatment and give rise to a large number of hospital admissions as a result of medically important, sometimes serious or even fatal adverse events. Drug-drug interactions can also cause partial or complete abolishment of treatment efficacy. The ageing European population, where polypharmacy is more frequent, increases the likelihood of such interactions and underlines the importance of a scientifically sound understanding of the potential for drug-drug interactions for all new chemical entities. A number of drugs have been withdrawn from the market as a result of drug-drug interactions that were only discovered post-marketing. The potential for drug-drug interactions is considered in the benefit-risk evaluation of a medicinal product and can negatively impact on this balance either through increased incidence of adverse events or reduced efficacy.
The potential for pharmacokinetic interactions between new medicinal products and already marketed drugs should be evaluated. This applies to both effects of the medicinal product on other drugs as well as the effect of other drugs on the medicinal product. Furthermore the effect of concomitant food intake needs to be investigated. The drug-drug interaction potential is usually investigated through in vitro studies followed by in vivo studies. The results of interaction studies are used to predict a number of other interactions based on the mechanisms involved. Treatment recommendations are developed based on the clinical relevance of the interactions and the possibility to make dose adjustments or treatment monitoring. This document aims to provide recommendations on all these issues. General recommendations are also provided for herbal medicinal products.
This guideline outlines a comprehensive, systematic and mechanistic approach to the evaluation of the interaction potential of a drug during its development and offers guidance to ensure that the prescriber receives clear information on the interaction potential as well as practical recommendations on how the interactions should be managed during clinical use.
The aim of the interaction studies performed on new medicinal products under development is to gain knowledge of how the new medicinal product affects the safety and efficacy of other medicinal products and vice versa. The potential for interactions is mainly investigated before marketing of a drug. Knowledge about the interaction potential should be gained as early as practically possible to assure safety during clinical phase II and III studies, as well as during clinical use after approval. Additional studies may be needed post-approval to optimize drug safety and to support treatment recommendations in the labeling and variation applications, e.g. for new indications or new dose recommendations. There may also be a need to perform additional studies due to emerging science or as a result of suspected drug interactions reported post marketing. The marketing authorization holder is advised to perform and report interaction studies as needed during the full life-cycle of the medicinal product.
This document provides recommendations on the pharmacokinetic and pharmacodynamic drug-drug interaction studies as well as food-drug interaction studies to be conducted including advice on study design, presentation of study results and translation of these results to treatment recommendations in the labeling of the drug. General advice is also given for herbal medicinal products.
It is recognized that the program to adress the interaction potential of an individual drug needs to be tailored to the specific drug. Alternative approaches are acceptable if adequately justified and driven by science and the expected clinical consequence of the interaction.