Search

Temporary Recommendations for Use (TRU) are a unique framework created by a French law (2011) to regulate and ensure a better safety for some off-label prescriptions.This measure was first applied to baclofen, widely prescribed off-label for treatment of alcohol use disorders by general practitioners since 2008. This off-label prescription involves over 10 000 prescribers and 100 000 patients. A TRU was thereby created to frame this prescription in March 2014, but one year later only 5000 patients were enrolled.Using qualitative research, we have studied the obstacles and incentives for the application of this TRU. We interviewed individually 15 general practitioners about their experience with the TRU. The main obstacles were the complexity of the TRU in everyday practice, and the lack of information, even though prescribers often wanted to participate to pharmacovigilance or to support baclofen. Some practitioners were suspicious and anxious, and considered the TRU a method of surveillance ; but generally the idea of regulating off-label drug use was thought necessary.This results in a non or incomplete application of the TRU. A revision of the TRU including its simplification is planned while waiting for a probable drug approval in the future.; Le dispositif des RTU (Recommandations Temporaires d’utilisation), unique au monde, a été créé dans le cadre de la loi relative au renforcement de la sécurité sanitaire du médicament de 2011 afin d’encadrer, sécuriser et suivre certaines prescriptions hors AMM.La première RTU concerne le baclofène et est à ce jour la seule qui concerne les médecins généralistes. Depuis 2008, la prescription hors AMM du baclofène dans l’indication du traitement des troubles de l’usage de l’alcool s’est fortement développée et concerne plus de 100 000 patients et 10 000 prescripteurs. Cette RTU, très demandée, a été accordée en mars 2014. Or les premiers bilans sont décevants : un net manque de participation des prescripteurs est constaté avec seulement 5000 patients inscrits en un an.Par une méthode qualitative, nous avons étudié les freins et motivations à l’application de cette RTU. 15 médecins généralistes aux profils variés ont été interrogés individuellement au sujet de leur vécu de la RTU. Les principaux freins sont la lourdeur du dispositif et la difficulté de son application pratique en médecine générale, ainsi que le manque d’information, malgré souvent un souhait de participer dans un objectif de pharmacovigilance ou de soutien au médicament. Nombre de praticiens ont exprimé une méfiance sur ce dispositif, anxiogène, et perçu comme une surveillance du médecin. Le principe d’un encadrement du hors AMM est souvent qualifié de nécessaire, à condition qu’il soit plus adapté. Il en résulte une non application ou une application incomplète du dispositif. Une révision et une simplification de la RTU est prévue prochainement dans l’attente d’une éventuelle AMM.

Bone morphogenetic proteins (BMP) are recombinant osteoinductive proteins with their primary role being to promote bone formation. The off-label use of BMP in orthopaedic surgery has dramatically increased. However, reports of complications with BMP have emerged, and the safety of these proteins in orthopaedics is questioned. The purpose of this review was to evaluate safe situations in which BMP should be used and situations in which their use should be restricted.We recorded all studies from PubMed database from 2002 (date of first authorisation for both BMPs) until January 2014 using "BMP" or "bone morphogenetic protein". Then we screened and extracted all studies dealing with orthopaedic surgery. All situations in which BMP were used, even cases reports, were considered, and complications reported were then listed.Situations in which it seems safe and efficient to use BMP are long-bone nonunions, or arthrodesis as an alternative or combined to autograft in small-bone loss. Surgeons and patients should be aware of transient aseptic wound swelling when BMP is located superficially. The use of BMP in spine surgery for intersomatic fusion is efficient but should be restricted to approaches that respect the vertebral canal to avoid neurological complications.This review is an off-label map of BMP use in orthopaedics during the past 10 years. Our results could provide a useful tool to help decisions around when to use a BMP in a specific complex, and sometimes off-label, situation.

International audience; Mineralocorticoid receptor (MR) antagonism is a well-established treatment modality for patients with hypertension, heart failure, and left ventricular systolic dysfunction (LVSD) post-myocardial infarction (MI). There are emerging data showing potential benefits of MR antagonists in other cardiovascular conditions. Studies have shown association between MR activation and the development of myocardial fibrosis, coronary artery disease, metabolic syndrome, and cerebrovascular diseases. This review examines the preclinical and clinical data of MR antagonists for novel indications including heart failure with preserved ejection fraction (HFPEF), pulmonary arterial hypertension (PAH), arrhythmia, sudden cardiac death, valvular heart disease, metabolic syndrome, renal disease, and stroke. MR antagonists are not licensed for these conditions yet; however, emerging data suggest that indication for MR antagonists are likely to broaden; further studies are warranted.

International audience; Used in the treatment of spasticity at low doses, baclofen is also prescribed off-label at high doses for the treatment of alcohol dependence. Several cases of baclofen intoxication have been reported, but only 1 case deals with the treatment of alcohol dependence. Thus, we report the first death in the context of baclofen off-label use of an alcohol-dependent patient with a high blood baclofen concentration after intentional drug intoxication. The safety profile of baclofen in the treatment of alcohol dependence is reviewed and discussed, underlining the obligatory caution that may support any prescription of high doses of baclofen in this off-label indication and especially in patients with concomitant psychiatric disorders.

International audience