Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Regulatory and Practical Risk Management of Potential Drug-Drug Interactions

Martin Knieps (Abschlußjahr: 2010)

Language: English

Drug-drug interactions may be defined as any modification of the effects of a medicinal product when administered concomitantly with another medicinal product. Possible consequences of drug-drug interactions are diverse and may range from beneficial to fatal, thus representing a potential risk for patients. An overall incidence of drug-drug interaction could not be determined as all approaches conducted so far only estimated the incidence of either any potential or only serious known drug-drug interaction.

The scientific progress in the evaluation of drug-drug interactions has been large in the last decade. The current regulatory guidance documents in the European Union on the investigation of drug-drug interactions did lately not keep up with these developments and need to be updated. Several key issues were briefly discussed in this Master thesis. However, in the end it will remain impossible to cover all risk factors of drug-drug interaction by specific interaction studies and a best possible case by case assessment of available data will always be required.

Most importantly for the (regulatory) management of drug-drug interaction is the adequate and comprehensive transfer of the data on known drug-drug interactions into the information texts. This is because all information, which is distributed by the pharmaceutical industry, whether advertising or not, have to be in agreement with the approved summary of product characteristics (SmPC).

The package information leaflet (PIL) also has to be in accordance with the SmPC. However, in the opinion of the author, the increasing knowledge on drug-drug interactions is too complex to be directly communicated to non-healthcare professionals. Key elements of information on drug-drug interactions for patients were thus defined in this Master thesis. The current transfer of information, exemplified in this thesis in the comparison of the PILs for amitripyline, hypericum perforatum and duloxetine from Germany, Switzerland and the Netherlands, is heterogenous and partially not well suited.

The practical management of drug-drug interaction should be clearly assigned to physicians for medicinal products on prescription and pharmacists for OTC products. At this task, the biggest problem is that contradictory information on drug-drug interaction is currently available from different sources like SmPCs, textbooks or commercial electronic systems. The large amount of alerts on potential drug-drug interactions by electronic systems have led to an “alert fatigue” of healthcare professionals. Unification, simplification and a general reduction of the amount of information is thus required.

Still the SmPC should be used to provide as broad information on drug-drug interactions as available. However, an improvement in structure in the presentation and a categorization of drug-drug interactions by their potential relevance is required. For this purpose, the establishment of a common evaluation scheme is required. The author of this Master thesis has defined the relevance of a drug-drug interaction as follows: "A relevant drug-drug interaction for a patient is an interaction which resulted in any untoward effect of any severity or a treatment outcome less then could reasonably have been expected and (in both cases) required any change of medical treatment or any treatment monitoring. It is either probable that the interaction will also occur in other patients or the possible consequences are serious and will possibly occur in other patients. Exception: A strong theoretic concern may also qualify as a relevant drug-drug interaction". The deduction of this definition, its interpretation and its practical use are presented in this Master thesis.

Other possibilities to regulate or improve the practical management are trainings on the mechanisms of drug-drug interaction for healthcare professionals, general training of patient attitude towards medicinal products and regulation by the control of dispensation of medicinal products.

Overall, there are multiple ways to improve the management of drug-drug interactions and in consequence to reduce the respective risks for patients.

Pages: 46, annexes: 3 pages