Muscle Damage Due to Fusidic Acid-Statin Interaction: Review of 75 Cases From the French Pharmacovigilance Database and Literature Reports.

BACKGROUND/AREA OF UNCERTAINTY: Statins, which reduce cardiovascular risk in both primary and secondary prevention, are one of the most widely prescribed therapeutic classes in the world. Usually well-tolerated, statin-associated muscle symptoms are a well-known adverse effect. Fusidic acid (FA) is a bacteriostatic antibiotic of interest in the treatment of methicillin-resistant Staphylococcus aureus infections. Cases of rhabdomyolysis, sometimes fatal, have been reported after coprescription of FA and a statin. DATA SOURCES/AREA OF UNCERTAINTY: We studied 75 cases of muscle damage related to interaction between FA and a statin reported in the French national pharmacovigilance database (43 cases) and from a literature review (32 cases). RESULTS: Cases were mostly men (72.5%), often overweight (mean body mass index: 29.4). The most commonly reported statins were atorvastatin (60%), simvastatin (22.7%), and rosuvastatin (8.0%). Muscle disorders appeared on average 30 days after initiation of FA. Symptoms were muscle weakness (82%), dark urine (71%), and myalgia (61%). Mean creatine kinase level at diagnosis was 43,890 UI/mL, and acute renal injury occurred more than half of the cases. Outcome was fatal in 22% of cases and 28% kept sequelae at the end of the follow-up (54 days). CONCLUSIONS: Muscle damage induced by interaction between FA and statin is a potentially life-threatening complication, leading to contraindication of this association in France. This is to be reminded especially because FA is about to get FDA approval and should soon be available in the United States.

Nicorandil and cutaneous ulcerations, their misdiagnosis and consequences: Illustration by five cases reports and a review of the French pharmacovigilance database.

While physicians increasingly recognize nicorandil-related mucocutaneous ulcerations, there are still misdiagnoses, particularly in the case of unusual location and late onset ulceration after nicorandil introduction. The goal of our study was to remind clinicians about the link between nicorandil use and the development of cutaneous ulcerations and to highlight the risk of misdiagnosis. We describe five reports diagnosed by the same dermatologist, complemented by an analysis of the French pharmacovigilance database (FPVD) from 1 January 1994 to 5 January 2017. During this period, 28 reports of strict cutaneous ulcerations due to nicorandil, in addition to our five reports, were registered in the FPVD. For those 28 reports, the time to onset between nicorandil introduction and cutaneous ulcerations was quite long and exceeded one year in 16 reports (information specified in 25 reports). The delay between ulcerations observation and nicorandil discontinuation was variable, with immediate diagnosis in seven reports, but ranged from fifteen days to twelve years in 21 reports. The main locations were lower limbs, thorax and face. Ulcerations could be localized on surgery or trauma scars. Regression after nicorandil discontinuation was observed in all but two reports and ranged from three days to three months. Characteristics were comparable in our five patient's series. All patients exposed to nicorandil and healthcare practitioners prescribing nicorandil should be aware of the risk of cutaneous ulcerations to enable early diagnosis and drug withdrawal. The risk of misdiagnosis of this serious adverse drug reaction, along with the risk of sequelae, the costs of unnecessary additional investigations and the recent update on nicorandil as second-line treatment for stable angina, with existing alternative drugs, question about the benefit/risk balance of nicorandil.

Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use.

Direct oral anticoagulants: Current indications and unmet needs in the treatment of venous thromboembolism.

The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor IIa. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase-III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery.

Exposure to aripiprazole during embryogenesis: a prospective multicenter cohort study.

PURPOSE: The main purpose of this study was to evaluate the risk of major malformations after aripiprazole exposure during the embryonic period. The secondary purposes were to assess the risk of miscarriage, prematurity, fetal growth retardation and maternal complications and to describe possible neonatal adverse effects. METHODS: We conducted a cohort study using data prospectively collected by the French Pharmacovigilance Centres participating to the Terappel program and the Centre de Référence sur les Agents Tératogènes between 2004 and 2011. The exposed group consisted of pregnant women exposed to aripiprazole during embryogenesis, and the unexposed group consisted of pregnant women without exposure or exposed to non-teratogenic agents. Two unexposed patients, matched for age and gestational age at call, were randomly selected for each exposed patient. RESULTS: Eighty-six patients were included in the exposed group and 172 in the unexposed group. Exposure to aripiprazole was not significantly associated with an increased rate of major malformations (OR 2.30, 95%CI 0.32-16.7) or miscarriage (1.66, 0.63-4.38) or gestational diabetes (1.15, 0.33-4.04) compared to non-exposure. The study revealed significantly increased rates of prematurity (OR 2.57, 95%CI 1.06-6.27) and fetal growth retardation (2.97, 1.23-7.16) in exposed newborns, difficult to interpret because of the short duration of maternal exposure. Two cases of neonatal complications were reported among the 19 newborns exposed to aripiprazole near delivery. CONCLUSION: This study failed to demonstrate a significant association between aripiprazole exposure during the embryonic period and major malformations. More powerful prospective studies are required to clarify the reproductive safety profile of aripiprazole.

Adverse Drug Reaction Identification and Extraction in Social Media: A Scoping Review.

BACKGROUND: The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients' experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance. OBJECTIVE: A scoping review was undertaken to explore the breadth of evidence about the use of social media as a new source of knowledge for pharmacovigilance. METHODS: Daubt et al's recommendations for scoping reviews were followed. The research questions were as follows: How can social media be used as a data source for postmarketing drug surveillance? What are the available methods for extracting data? What are the different ways to use these data? We queried PubMed, Embase, and Google Scholar to extract relevant articles that were published before June 2014 and with no lower date limit. Two pairs of reviewers independently screened the selected studies and proposed two themes of review: manual ADR identification (theme 1) and automated ADR extraction from social media (theme 2). Descriptive characteristics were collected from the publications to create a database for themes 1 and 2. RESULTS: Of the 1032 citations from PubMed and Embase, 11 were relevant to the research question. An additional 13 citations were added after further research on the Internet and in reference lists. Themes 1 and 2 explored 11 and 13 articles, respectively. Ways of approaching the use of social media as a pharmacovigilance data source were identified. CONCLUSIONS: This scoping review noted multiple methods for identifying target data, extracting them, and evaluating the quality of medical information from social media. It also showed some remaining gaps in the field. Studies related to the identification theme usually failed to accurately assess the completeness, quality, and reliability of the data that were analyzed from social media. Regarding extraction, no study proposed a generic approach to easily adding a new site or data source. Additional studies are required to precisely determine the role of social media in the pharmacovigilance system.

Efficacy of baclofen on abstinence and craving in alcohol-dependent patients: a meta-analysis of randomized controlled trials.

PURPOSE: We conducted a meta-analysis in order to estimate the efficacy of baclofen on the maintenance of abstinence and the decrease of craving in alcohol-dependent patients. METHODS: All randomized controlled clinical trials assessing baclofen for at least four weeks' treatment duration versus placebo or other comparators were included. The primary outcome measure was the percentage of patients who had not consumed alcohol at the end of the treatment. Measures of cumulative abstinence and indexes of craving were also assessed. RESULTS: Compared to placebo, baclofen was associated with a significant increase of 179% in the percentage of abstinent patients at the end of the trial, without heterogeneity. For secondary outcome measures, based on a random-effect model, no significant effect of baclofen was observed compared to placebo. CONCLUSIONS: Our meta-analysis brings weak support towards an efficacy of low dosages of baclofen on the maintenance of abstinence in alcohol-dependent patients.

[Drug-related anaphylactic shocks: under-reporting and PMSI]. / Chocs anaphylactiques d'origine médicamenteuse: sous-notification et PMSI.

AIM: To evaluate the value of research in the case-mix database to identify cases of drug-related anaphylactic or anaphylactoid shock. METHODS: Hospital stays of patients discharged from the University Hospital of Saint-Étienne between July 1st 2009 and June 30th 2012. Five codes from the international classification of diseases were selected: T88.6, T88.2, J39.3, T80.5 and T78.2. RESULTS: Among 89 cases identified by the programme for medicalization of information system (programme de médicalisation des systèmes d'information, PMSI), 40 were selected (45%). Of these, 16 cases were spontaneously reported by physicians. The unspecific code "anaphylactic shock unspecified (T78.2)" was coded for 57.5% of cases. CONCLUSION: The study confirms the interest of the PMSI as a tool for health monitoring, in addition to spontaneous reporting. Nevertheless, coding with insufficient precision about the causal role of the drug, requires a return to the medical record and so an important time consuming process.

[Not Available]. / Chocs anaphylactiques d'origine médicamenteuse : sous-notification et PMSI.

AIM: To evaluate the value of research in the case-mix database to identify cases of drug-related anaphylactic or anaphylactoid shock. METHODS: Hospital stays of patients discharged from the University Hospital of Saint-Étienne between July 1st 2009 and June 30th 2012. Five codes from the international classification of diseases were selected: T88.6, T88.2, J39.3, T80.5 and T78.2. RESULTS: Among 89 cases identified by the programme for medicalization of information system (programme de médicalisation des systèmes d'information, PMSI), 40 were selected (45%). Of these, 16 cases were spontaneously reported by physicians. The unspecific code "anaphylactic shock unspecified (T78.2)" was coded for 57.5% of cases. CONCLUSION: The study confirms the interest of the PMSI as a tool for health monitoring, in addition to spontaneous reporting. Nevertheless, coding with insufficient precision about the causal role of the drug, requires a return to the medical record and so an important time consuming process.

Complications of BCG vaccine SSI® recent story and risk management plan: the French experience.

INTRODUCTION: As of January 2006, the BCG vaccine SSI® became the only BCG vaccine available for tuberculosis vaccination in France. The use of this vaccine led to significant changes in vaccination technique which were accompanied by a rapid increase in the number of adverse reactions (ADRs) reported. A national pharmacovigilance follow-up began in February 2006, and a risk management plan (RMP) was put in place in April 2006, made of three phases (carried out in June 2006, July 2006 and September 2006) with risk minimisation measures. The goal of this study was to evaluate the impact of the RMP on the amount of ADRs reported. METHODS: Based on data collected by the regional pharmacovigilance centres and the MSD laboratory, the cases of locoregional ADRs spontaneously reported were analysed retrospectively from January 2005 to February 2006, and then prospectively up to June 2008, the date at which the national follow-up ended. The locoregional ADRs were divided into three categories: abscesses, local reactions or lymphadenopathy of more than 1 cm and suppurative lymphadenopathy. A parallel was then drawn between these data and the different phases of the RMP. RESULTS: During the entire follow-up period, we note 1050 locoregional ADRs, of which 764 were abscesses (73% of all cases), 266 were local reactions and 20 involved suppurative lymphadenopathy.Locoregional ADRs increased rapidly from January 2006 onward, reaching a peak in August 006 and then falling and stabilising from December 2007 onward.The RMP was implemented when there was an increase in the number of ADRs reported. The drop in the number of these effects began 3 months after the first phase and 2 months after the second phase of the RMP. The third phase was not accompanied by a variation in the number of ADRs reported. CONCLUSION: The RMP appears to have positive effect on the evolution of the number of ADRs, their decrease occurring rapidly after the risk minimisation measures of the first two phases. Nonetheless, these data should be confirmed by other studies on the efficacy of RMPs.

[Severe meprobamate poisoning: description of 146 cases in a French department]. / Intoxications graves au méprobamate : description d'une série de 146 cas dans le département de la Loire.

Meprobamate poisoning are serious and sometimes fatal. Faced with a potential stop of marketing, we conducted a multicenter retrospective study to assess the severity criteria presented by patients admitted to the ICU for severe meprobamate poisoning, whether with alone form or in combination with aceprometazine. One hundred fourty-six patients have been enrolled between January 2005 and June 2011: 38 had a single meprobamate poisoning, 104 to meprobamate and aceprometazine and 4 to both forms. At admission, 88% of patients exhibited coma (Glasgow ≤ 7) and half of them a systolic blood pressure ≤ 90 mmHg. Mortality rate was 3%. Our results did not find any significant between-group difference, either in regard of clinical or biological severity criteria. These data argue for a cessation of marketing of all meprobamate-based specialities.

[Drug induced hyponatremia. About a series of 54 cases notified to the regional center of pharmacovigilance of Saint-Étienne]. / Hyponatrémies d'origine médicamenteuse. À propos d'une série de 54 cas notifiés au Centre Régional de Pharmacovigilance de Saint-Étienne.

OBJECTIVE: Analyze the most frequently reported drug in iatrogenic hyponatremia, explaining the mechanism in question. METHODS: Retrospective study on 54 notified cases between the Jan.1(st) 2003 and Dec. 31(st) 2009. The analysis focuses on drug classes, accountability and mechanism; risk factors, severity and the evolution of the case. RESULTS: Fourty-nine cases have been retained, 75,5% of the time it was an inappropriate secretion of antidiuretic hormone (SIADH) involving a selective serotonin reuptake inhibitor (SSRI) in 15 cases, an anticonvulsant in 7 cases, a proton pump inhibitor (PPI) in 7 cases or other drugs in 11. The hypo-osmolar hypovolemic hyponatremia was 12.2% of cases, incriminating a thiazide diuretic once in two. The mechanism was different or indeterminate in 12.2% of cases. In 67% cases were serious. The evolution was often favourable. CONCLUSION: Drug induced hyponatremia can be serious. It must control natremia with patients at risk or symptomatic and conduct the etiological diagnosis.

Use of Social Media for Pharmacovigilance Activities: Key Findings and Recommendations from the Vigi4Med Project.

The large-scale use of social media by the population has gained the attention of stakeholders and researchers in various fields. In the domain of pharmacovigilance, this new resource was initially considered as an opportunity to overcome underreporting and monitor the safety of drugs in real time in close connection with patients. Research is still required to overcome technical challenges related to data extraction, annotation, and filtering, and there is not yet a clear consensus concerning the systematic exploration and use of social media in pharmacovigilance. Although the literature has mainly considered signal detection, the potential value of social media to support other pharmacovigilance activities should also be explored. The objective of this paper is to present the main findings and subsequent recommendations from the French research project Vigi4Med, which evaluated the use of social media, mainly web forums, for pharmacovigilance activities. This project included an analysis of the existing literature, which contributed to the recommendations presented herein. The recommendations are categorized into three categories: ethical (related to privacy, confidentiality, and follow-up), qualitative (related to the quality of the information), and quantitative (related to statistical analysis). We argue that the progress in information technology and the societal need to consider patients' experiences should motivate future research on social media surveillance for the reinforcement of classical pharmacovigilance.

Pharmacology and social media: Potentials and biases of web forums for drug mention analysis-case study of France.

The aim of this study is to analyze drug mentions in web forums to evaluate the utility of this data source for drug post-marketing studies. We automatically annotated over 60 million posts extracted from 21 French web forums. Drug mentions detected in this corpus were matched to drug names in a French drug database (Theriaque®). Our analysis showed that a high proportion of the most frequent drug mentions in the selected web forums correspond to drugs that are usually prescribed to young women, such as combined oral contraceptives. The most mentioned drugs in our corpus correlated weakly to the most prescribed drugs in France but seemed to be influenced by events widely reported in traditional media. In this article, we conclude that web forums have high potential for post-marketing drug-related studies, such as pharmacovigilance, and observation of drug utilization. However, the bias related to forum selection and the corresponding population representativeness should always be taken into account.

Case report: Recurrent peripheral facial paralysis following two influenza vaccinations in 2009 and 2016.

A 57-year-old female experienced two successive peripheral facial paralysis (PFP) episodes following influenza immunization in 2009 and 2016 with two different vaccines. The similarity of chronology and semiology between the two events and the absence of alternative etiology plead for intrinsic accountability. Extrinsic accountability relies on previous case reports of PFP related to flu vaccination (26 cases in the French pharmacovigilance database and 4 cases in the medical literature).

Serious adverse reactions of bupropion for smoking cessation: analysis of the French Pharmacovigilance Database from 2001 to 2004.

BACKGROUND: Bupropion was the first alternative to nicotine replacement therapy in the pharmacological treatment for smoking cessation. Its safety profile has been monitored in France via spontaneous reporting. OBJECTIVE: To describe all serious adverse reactions (SARs) reported in France since the marketing authorization for bupropion in September 2001, and to analyse risk factors for these SARs. DESIGN: We collected all spontaneous reports of adverse reactions to bupropion received by all French Regional Pharmacovigilance Centres and by GlaxoSmithKline, the manufacturer of bupropion, during the first 3 years of marketing of this agent. We identified the characteristics of the population to whom bupropion was prescribed from the Thales database, which contains information obtained from a representative sample of general practitioners in France. We then compared the population with SARs with the population prescribed the drug (exposed population) to identify possible risk factors such as sex, age and daily dose for the most frequent SARs. RESULTS: Bupropion was prescribed to 698 000 patients during the first 3 years of marketing in France. In these patients, 1682 cases of adverse reactions were reported; 28% of these involved SARs, mainly cutaneous or allergic reactions (31.2%), including angioedema and serum sickness-like reactions. Serious neurological reactions were frequent (22.5%), mostly comprising seizures; however, questioning revealed that almost half of these patients had a history of seizures or other risk factors. Of the serious neuropsychiatric adverse events reported (17.3%), suicide attempts/suicides were a cause for concern, although risk factors (history of depression, suicide attempts, etc.) were described for 66% of patients experiencing these events. Patients reporting angioedema and serum sickness-like reactions, and those involved in suicide attempts/suicides, were significantly younger than the exposed population. A dose-dependent effect was also apparent for angioedema and for seizures. Cardiovascular SARs, such as ischaemic heart disease (10.1%) or sudden death (2.3%), were very often associated with pre-existing coronary artery disease induced by smoking. All these SARs occurred within a median of 12-14 days after drug initiation. CONCLUSION: To ensure safer use of bupropion, health professionals must respect the strict contraindications and warnings about use of this drug in patients with a history of seizures. Seizures, angioedema and serum sickness-like reactions were the most frequently reported SARs to bupropion treatment in our study. Moreover, younger people appeared to be more at risk for cutaneous SARs generally, and younger women for angioedema in particular, perhaps because of weight-related differences in pharmacokinetics. A dose-dependent effect for angioedema and the results of skin tests were suggestive of a histamine liberation mechanism. Our analysis showed that taking more notice of the contraindications to use of bupropion could have prevented half the seizures reported to the database. The sex and age characteristics of patients with ischaemic heart disease and suicide attempts in the study population were similar to those of the French population as a whole. Whether bupropion is associated with an increase in these potential adverse effects of therapy can be determined only by epidemiological studies that take into account specific risk factors in the smoking population. Finally, the median time to onset of the SARs identified in this study suggests that prescribers should monitor patients exposed to bupropion more carefully during the first 2 weeks of treatment.

Evaluating Twitter as a complementary data source for pharmacovigilance.

BACKGROUND: Social media are currently considered as a potential complementary source of knowledge for drug safety surveillance. Our primary objective was to estimate the frequency of adverse drug reactions (ADRs) experienced by Twitter users. Our secondary objective was to determine whether tweets constitute a valuable and informative source of data for pharmacovigilance purposes, despite limitations on character number per tweet. RESEARCH DESIGN AND METHODS: We selected a list of 33 drugs subject to careful monitoring due to safety concern in France and Europe, and extracted tweets using the streaming API from 30 September 2014 to 5 April 2015. Two pharmacovigilance centers classified these tweets manually as potential ADR case reports. RESULTS: Among 10,534 tweets, 848 (8.05%) implied or mentioned an ADR without meeting the four FDA criteria required for reporting an ADR, and 289 (2.74%) tweets were classified as 'case reports.' Among them 20 (7.27%) tweets mentioned an unexpected ADR and 33 (11.42%) tweets mentioned a serious ADR. CONCLUSIONS: With the use of dedicated tools, Twitter could become a complementary source of information for pharmacovigilance, despite a major limitation regarding causality assessment of ADRs in individual tweets, which may improve with the new limitation to 280 characters per tweet.

Descriptions of Adverse Drug Reactions Are Less Informative in Forums Than in the French Pharmacovigilance Database but Provide More Unexpected Reactions.

Background: Social media have drawn attention for their potential use in Pharmacovigilance. Recent work showed that it is possible to extract information concerning adverse drug reactions (ADRs) from posts in social media. The main objective of the Vigi4MED project was to evaluate the relevance and quality of the information shared by patients on web forums about drug safety and its potential utility for pharmacovigilance. Methods: After selecting websites of interest, we manually evaluated the relevance of the content of posts for pharmacovigilance related to six drugs (agomelatine, baclofen, duloxetine, exenatide, strontium ranelate, and tetrazepam). We compared forums to the French Pharmacovigilance Database (FPVD) to (1) evaluate whether they contained relevant information to characterize a pharmacovigilance case report (patient's age and sex; treatment indication, dose and duration; time-to-onset (TTO) and outcome of the ADR, and drug dechallenge and rechallenge) and (2) perform impact analysis (nature, seriousness, unexpectedness, and outcome of the ADR). Results: The cases in the FPVD were significantly more informative than posts in forums for patient description (age, sex), treatment description (dose, duration, TTO), and outcome of the ADR, but the indication for the treatment was more often found in forums. Cases were more often serious in the FPVD than in forums (46% vs. 4%), but forums more often contained an unexpected ADR than the FPVD (24% vs. 17%). Moreover, 197 unexpected ADRs identified in forums were absent from the FPVD and the distribution of the MedDRA System Organ Classes (SOCs) was different between the two data sources. Discussion: This study is the first to evaluate if patients' posts may qualify as potential and informative case reports that should be stored in a pharmacovigilance database in the same way as case reports submitted by health professionals. The posts were less informative (except for the indication) and focused on less serious ADRs than the FPVD cases, but more unexpected ADRs were presented in forums than in the FPVD and their SOCs were different. Thus, web forums should be considered as a secondary, but complementary source for pharmacovigilance.

[Severe renal adverse events with arylcarboxylic non-steroidal anti-inflammatory drugs: results of a eight-year French national survey]. / Atteintes rénales graves au cours d'un traitement par anti-inflammatoires non stéroidiens arylcarboxyliques: bilan d'une enquête nationale de pharmacovigilance.

The non-steroidal anti-inflammatory drugs (NSAID) especially the arylcarboxylic, are widely prescribed for their different properties. The renal adverse events are rare but often serious. We have reviewed the French experience for the following eight years period: January 1995 to December 2002. Three hundred and nine cases have been reported to the French Pharmacovigilance system during that period including 275 adults, 29 children and 5 new-born babies. In 247 cases (80%), the presentation was an acute renal failure occurring few days after treatment onset but not always of the prerenal type. Overall 34 patients needed one or more dialysis session; the majority recovered either completely or partially, but nevertheless, we had to deplore 5 deaths. These major renal complications were observed with all available NSAID on the French market, including ibuprofen which was often prescribe as pain-reliever. With this data together with international information, the French Drug Agency decided to modify the summary of products characteristics of these NSAID.

[Not Available]. / Atteintes rénales graves au cours d'un traitement par anti-inflammatoires non stéroïdiens arylcarboxyliques : bilan d'une enquête nationale de pharmacovigilance.

The non-steroidal anti-inflammatory drugs (NSAID) especially the arylcarboxylic, are widely prescribed for their different properties. The renal adverse events are rare but often serious. We have reviewed the French experience for the following eight years period: January 1995 to December 2002. Three hundred and nine cases have been reported to the French Pharmacovigilance system during that period including 275 adults, 29 children and 5 new-born babies. In 247 cases (80%), the presentation was an acute renal failure occuning few days after treatment onset but not always of the prerenal type. Overall 34 patients needed one or more dialysis session; the majority recovered either completely or partially, but nevertheless, we had to deplore 5 deaths. These major renal complications were observed with all available NSAID on the French market, including ibuprofen which was often prescribe as pain-reliever. With this data together with international information, the French Drug Agency decided to modify the summary of products characteristics of these NSAID.