Through the looking glass: drug safety in the light of pharmacogenomics, drug interactions and beyond

The monitoring of drug safety is essential so as to be sure that the drugs that are on the market are safe, effective and of good quality. The activity that monitors this drug safety is called pharmacovigilance and consists in detecting, assessing understanding and preventing adverse drug reactions or any other drug-related problem. This thesis aims to describe the process of drug safety throughout the drug’s life-cycle, process that goes hand-in-hand with every stage of the development of the drug but continues also in the postmarketing phase once the drug is given to real-life patients. After going through the history of drug safety and the burden of adverse drug reactions, we attempt to put forward the usefulness of clinical trials in acquiring a first safety profile of a new drug in a carefully selected population but also the limitations of these clinical trials in detecting rare, unknown adverse drug reactions in real-life situations. The different means by which the gaps in drug safety can be further filled in are explained, from spontaneous adverse drug reporting systems to pharmacoepidemiologic studies, means that allow collecting data on special populations such as elderly patients, children and pregnant women or in special situations such as drug misuse, drug-drug interactions and particular pharmacogenetic profiles. Finally, we review how the monitoring of drug safety can be further improved, using new technologies and better communication

Topical corticosteroid-induced skin atrophy: a comprehensive review

Skin atrophy is an adverse effect of topical corticosteroids (TCs) which, as an established non-life-threatening effect, has been poorly reported by trials involving these drugs. Atopic dermatitis and psoriasis are example of disorders that require repeated therapies with TCs; however, assessing the atrophogenic activity of TCs is still an issue. This study aims to review clinical data on skin atrophy induced by TCs. Searches of the PubMed, EMBASE, and Cochrane (Central) databases from 1965 to May 2013 were undertaken using the keywords 'corticosteroid', 'skin', and 'atrophy'. Skin and epidermal thickness values were retrieved from trials on healthy skin, and studies including skin atrophy as a safety endpoint in trials testing the efficacy of TCs were analyzed. Overall, 60 articles were retrieved. Whole skin and epidermal thickness were relevant parameters to measure early skin atrophy on healthy skin before it becomes clinically obvious. Epidermis thickness also seems to be more sensitive than whole skin thickness in detecting early atrophy; however, measuring skin atrophy still requires standardization. Further clinical trials on the atrophic effects of each TC are required to better evaluate their respective atrophic risks and their risk/benefit ratios. However, measuring epidermal or whole skin thickness will not be relevant in acute phases of inflammatory skin disorders treated with TCs because of the thickening induced by inflammation. In addition, skin atrophy seems to be induced by chronic TC use rather than by acute treatments. Long-term safety studies may be more relevant to evaluate atrophic activity

Safety signal detection: the relevance of literature review

Adverse drug reactions (ADRs) represent an important risk for patients and have a significant economic impact on health systems. ADRs are the fifth most common cause of hospital death, with a burden estimated at 197,000 deaths per year in the EU. This has a societal cost of 79 billion per year. Because of this strong impact in public health, regulatory authorities (RAs) worldwide are implementing new pharmacovigilance legislation to promote and protect public health by reducing the burden of ADRs through the detection of safety signals. Although, traditionally, signal detection activities have mainly been performed based on spontaneous reporting from healthcare professionals and national health RAs, the new pharmacovigilance legislation underlines the relevance of other sources of information (such as scientific literature) for the evaluation of the benefit-risk balance of a certain product. This review aims to highlight the relevance of periodic scientific literature screening in the safety signal detection process. The authors present four practical examples where a safety signal that was detected from a literature report had an impact on the lifecycle of a drug. In addition, based on practical experience of the screening of medical and scientific literature for safety purposes, this article analyses the requirements of the new pharmacovigilance guidelines on literature screening and highlights the need for the implementation of a literature review procedure and the main challenges encountered when performing literature screening for safety aspects

Surprescription des inhibiteurs de la pompe à protons

Overutilization of proton pump inhibitors (PPI) is obvious despite available recommendations, with clinical and economical issues. This overuse is due to abusive stress ulcer prophylaxis and to automatic represcription, particularly during transitions from intensive care unit to other inhospital units and at hospital discharge. Withdrawal symptoms may contribute to the difficulty of PPI interruption. It is mandatory to limit initiation of PPI treatment outside of appropriate indications and to regularly reassess the need of this treatment

Reduction of polypharmacy in the elderly: a systematic review of the role of the pharmacist

Polypharmacy in the elderly complicates therapy, increases cost, and is a challenge for healthcare agencies. In the context of the evolving role of the pharmacist, this systematic review examines the effectiveness of interventions led by pharmacists in reducing polypharmacy. A computerised search was conducted using Medline, Embase geriatrics and gerontology (2001 edition), the Cochrane Library and International Pharmaceutical Abstracts (IPA) databases. A manual search of articles on polypharmacy and the role of pharmacists in the therapy of the elderly and of the reference sections of all retrieved articles was also carried out. Search terms used were 'polypharmacy', 'elderly', 'aged', 'intervention' and 'pharmacist(s)'. Articles that fulfilled the following criteria were included: only elderly people were included in the study, or all ages were included but the study gave separate results for the elderly; the outcome was expressed as a reduction in the number of medications; a pharmacist participated in the study; and the study was a controlled or a randomised controlled study. We initially identified 106 articles, but only 14 studies met our four inclusion criteria. Reduction in the number of medications was not the major purpose of most selected studies but often a secondary outcome. Objectives differed, the general aim being to enhance the quality of prescribing in elderly patients. These controlled studies argued in favour of the effectiveness of pharmacists' interventions, even though the number of medications eliminated was small. Most studies were not designed to demonstrate the impact of reducing the number of drugs on the clinical consequences of polypharmacy (nonadherence, adverse drug reactions, drug-drug interactions, increased risk of hospitalisation, and medication errors). The most frequently reported outcome related to cost savings. It was therefore difficult to assess whether the interventions benefited the patient. The methodological quality of many identified studies was poor. In particular, the study objectives were often very broad and ill-defined. Polypharmacy itself has been defined in different ways and the appropriate definition may differ according to the patient population and the study setting. Further studies are needed to find the most effective way to reduce polypharmacy, especially in the frail elderly population, and to quantify the real advantages of simplifying their drug regimens in terms of improved quality of life

Importance et particularités de la pharmacovigilance en pédiatrie

Les essais cliniques sont le plus souvent effectués sur une durée limitée et une population sélectionnée, excluant les enfants. Ils fournissent un premier profil de sécurité des médicaments, souvent partiel, ne mettant en évidence que les effets indésirables les plus fréquents. En pédiatrie, les phénomènes de croissance et de maturation peuvent être à l’origine de réactions aux médicaments différentes que chez l’adulte et empêchent la simple extrapolation à l’enfant des données, notamment de sécurité, obtenues chez l’adulte. La pharmacovigilance repose sur la notification spontanée des effets indésirables. Elle permet d’affiner le rapport risques/ bénéfices et d’augmenter la sécurité des médicaments une fois commercialisés. Cet article a pour but de souligner l’importance de la pharmacovigilance, en particulier dans la population pédiatrique, et de rappeler les modalités d’annonces

Effet analgesique des opiaces en usage cutane: quelle est leur efficacite?

Recent research has revealed the presence of opioid receptors in inflamed peripheral tissues. This gives rise to the possibility of treating the pain caused by wounds with the advantage of reducing the secondary effects related to the use of opioids and at the same time rendering their use more efficacious. The theory of a peripheral analgesic action of opioids has been tested in a variety of situations, in particular in brachial plexus blocks and intra-articular injections. In addition, the analgesic effect of opioids has been tested by cutaneous application for various conditions but on only a limited number of patients. On the basis of these case reports, we cannot conclude that the peripheral use of opioids is efficacious and the topical use of opioids cannot be recommended unless done within the framework of a controlled clinical trial