Risk of suicide attempt and suicide associated with benzodiazepine: A nationwide case crossover study.

BACKGROUND: Previous studies that found an association between benzodiazepines and suicidal behaviours were confounded by indication bias. AIMS: To limit this bias, a case crossover study (CCO) was conducted to estimate the risk of suicide attempt and suicide associated with benzodiazepines. METHOD: Patients ≥16 years, with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act were selected in the nationwide French reimbursement healthcare system databases (SNDS). For each patient, frequency of benzodiazepine dispensing was compared between a risk period (days -30 to -1 before the event) and two matched reference periods (days -120 to -91, and -90 to -61). RESULTS: A total of 111,550 individuals who attempted suicide and 12,312 suicide victims were included, of who, respectively, 77,474 and 7958 had recent psychiatric history. Benzodiazepine dispensing appeared higher in the 30-day risk period than in reference ones. The comparison yielded adjusted odds ratios of 1.74 for hospitalised suicide attempt (95% confidence interval 1.69-1.78) and 1.45 for suicide (1.34-1.57) in individuals with recent psychiatric history, and of 2.77 (2.69-2.86) and 1.80 (1.65-1.97) for individuals without. CONCLUSION: This nationwide study supports an association between recent benzodiazepine use and both suicide attempt and suicide. These results strengthen the need for screening for suicidal risk carefully before initiation and during treatment when prescribing benzodiazepines. REGISTRATION NO: EUPAS48070 (http://www.ENCEPP.eu).

Impact of the COVID-19 pandemic and its control measures on cardiovascular and antidiabetic drugs use in France in 2020: a nationwide repeated cohort study.

Since pandemic start, patients may have faced difficulties in accessing to care and treatment. This study aimed at assessing the impact of COVID-19 pandemic and its control measures on the use of drugs indicated in cardiovascular prevention and diabetes mellitus in France. From 09/17/2018 to 09/20/2020, a repeated cohort analysis was performed using the French nationwide health insurance databases. The pandemic impact was assessed using time-series analyses and unobserved components model for the weekly number of patients with (i) drug dispensing, (ii) ongoing treatment, (iii) treatment initiation, (iv) treatment disruption. Overall, 14,822,132 patients with cardiovascular drug dispensings and 3,231,618 with antidiabetic ones were identified. After a sharp spike in the amount of dispensings in the week the first national lockdown was announced, the period was marked by decreased levels and trends. Altogether, the estimated impact of the pandemic on dispensings appeared limited over the lockdown period (1-3% lack in dispensings). During lockdown, the weekly numbers of treatment disruptions remained stable whereas a significant decrease in treatment initiations was observed for almost all drug classes (e.g. ß-blockers initiations: - 8.9%). Conversely, the post-lockdown period showed increases in treatment disruptions especially for antihypertensive and lipid lowering drugs (e.g. statins disruptions: + 4.9%). The pandemic and associated measures had a significant impact on cardiovascular and antidiabetic drugs use in France, mostly consisting in decreases of treatment initiations over lockdown and increases in treatment disruptions afterwards. Both could result in increased morbimortality that remains to be assessed.

Risk of first ischaemic stroke and use of antidopaminergic antiemetics: nationwide case-time-control study.

OBJECTIVE: To estimate the risk of ischaemic stroke associated with antidopaminergic antiemetic (ADA) use. DESIGN: Case-time-control study. SETTING: Data from the nationwide French reimbursement healthcare system database Système National des Données de Santé (SNDS). PARTICIPANTS: Eligible participants were ≥18 years with a first ischaemic stroke between 2012 and 2016 and at least one reimbursement for any ADA in the 70 days before stroke. Frequencies of ADA reimbursements were compared for a risk period (days -14 to -1 before stroke) and three matched reference periods (days -70 to -57, -56 to -43, and -42 to -29) for each patient. Time trend of ADA use was controlled by using a control group of 21 859 randomly selected people free of the event who were individually matched to patients with stroke according to age, sex, and risk factors of ischaemic stroke. MAIN OUTCOME MEASURES: Association between ADA use and risk of ischaemic stroke was assessed by estimating the ratio of the odds ratios of exposure evaluated in patients with stroke and in controls. Analyses were adjusted for time varying confounders (anticoagulants, antiplatelets, and prothrombotic or vasoconstrictive drugs). RESULTS: Among the 2612 patients identified with incident stroke, 1250 received an ADA in the risk period and 1060 in the reference periods. The comparison with the 5128 and 13 165 controls who received an ADA in the same periods yielded a ratio of adjusted odds ratios of 3.12 (95% confidence interval 2.85 to 3.42). Analyses stratified by age, sex, and history of dementia showed similar results. Ratio of adjusted odds ratios for analyses stratified by ADA was 2.51 (2.18 to 2.88) for domperidone, 3.62 (3.11 to 4.23) for metopimazine, and 3.53 (2.62 to 4.76) for metoclopramide. Sensitivity analyses suggested the risk would be higher in the first days of use. CONCLUSIONS: Using French nationwide exhaustive reimbursement data, this self-controlled study reported an increased risk of ischaemic stroke with recent ADA use. The highest increase was found for metopimazine and metoclopramide.

Impact of pregnancy on antidepressant treatment course: a population-based comparative cohort study in France.

The prevention of relapses and the treatment of depression during pregnancy are difficult challenges. The maintenance of antidepressants in pregnancy with its concomitant risks to mother and child needs to be weighed against those associated with not treating the disease. This study aimed at quantifying the impact of the occurrence of pregnancy on the course of antidepressant treatment among newly treated women (< 6 months). We performed a comparative observational cohort study using the nationwide French reimbursement healthcare system database. Women who conceived in 2014 and initiated an antidepressant at any time in the 6 months before pregnancy were compared with nonpregnant women newly exposed to antidepressants with matching on age, antidepressant exposure, history of psychiatric disorders, and area of residence. The primary outcome was a composite of antidepressant discontinuation, switch to another antidepressant, and concomitant use of antidepressants. The secondary outcome was the resumption of antidepressant during follow-up. We used Cox marginal proportional hazards models to compare time to outcomes between pregnant and nonpregnant women. The pregnant cohort included 6593 women, and the comparison cohort 29,347 nonpregnant women. In the period following the first month of treatment, pregnant women were more likely to experience treatment modification, and especially to stop receiving it, compared with nonpregnant women (adjusted hazard ratio (aHR) 1.58; 95%CI, 1.51-1.62). Pregnant women who discontinued treatment had a 41% decreased incidence of antidepressant resumption compared with nonpregnant women (aHR 0.59; 95%CI, 0.56-0.62). Pregnancy was a determinant of antidepressant treatment modification, and especially of discontinuation.

Use of benzodiazepines and z-drugs not compliant with guidelines and associated factors: a population-based study.

Benzodiazepines and z-drugs are primarily indicated for the treatment of sleep disorders and anxiety symptoms. Their frequent long-term use contrasts with the international guidelines that limit treatment duration to a maximum of 4 weeks. The objective of this study was to assess the frequency of their use that was not in accordance with guidelines in the French general population between 2007 and 2012 and associated characteristics. A cohort of 67,550 benzodiazepine new users was set up in an exhaustive database for health-care reimbursements and representative of the French population. Benzodiazepine use not in accordance with guidelines was defined as the concomitant dispensation of several benzodiazepines, the dispensation of treatment over a period longer than recommended, or a new dispensing within the 2 months following the end of a previous treatment of maximum recommended duration, considering that French recommendations distinguish between hypnotic (4 weeks) and anxiolytic benzodiazepines (12 weeks). Benzodiazepine use not in accordance with guidelines was high, in about 30% of new hypnotic users and 20% of new anxiolytic users. Its frequency was stable over the study period. Associated characteristics were similar for new hypnotic or anxiolytic users, i.e.. older age, treatment initiation by a psychiatrist, presence of a chronic disease, hospitalization, or another psychotropic treatment. These findings provide a solid basis for establishing a public health policy to reduce benzodiazepine use not compliant with guidelines. They should be further explored in patients most at risk in the present study, e.g., patients treated by a psychiatrist.

Monitoring of drug misuse or potential misuse in a nationwide healthcare insurance database: A cross-sectional study in France.

AIM OF THE STUDY: To provide a tool for drug misuse or potential misuse monitoring by using a healthcare insurance database. METHODS: A cross-sectional study repeated quarterly from 2007 to 2014 was conducted using data from a 1/97th random sample of the French national healthcare reimbursement system. For each drug studied, ad hoc indicators were designed to assess drug misuse, defined as prescriptions that did not comply with the label stipulated in the summary of product characteristics, in terms of the drug (e.g., interactions) or the patient (age, medical history). We focused on specifically identified situations of drug misuse involving non-steroidal anti-inflammatory drugs (NSAIDs), antiemetics in patients with Parkinson's disease and antipsychotics in pediatrics; we also focused on direct anticoagulants, asthma and oral antidiabetic drugs but results for these latter are only shown in supplementary materials. RESULTS: At-risk prescribing of NSAIDs in patients treated by diuretics or renin-angiotensin system inhibitors always remained higher than 14% over the study (maximum: 19%; 2014 quarter 4: 15.4%). Off-label prescribing of contraindicated anti-dopaminergic antiemetics with dopaminergic antiparkinson drugs was marginal (maximum: 2.2%; 2014 quarter 4: 0.5%) but represented at least 5.5% of antiemetic prescriptions. Despite the rise in antipsychotic prescriptions in pediatrics, no dramatic increase in misuse related to age was observed during the study period (2007 quarter 1: 16.1%; 2014 quarter 4: 11.1%). The highest degree of misuse was observed for aripiprazole and for second-generation antipsychotics other than risperidone and aripiprazole. CONCLUSION: This study provides a simple tool to monitor drug misuse or potential misuse using information from a health insurance database. The results highlight the need for the Regulator to rethink risk management information campaigns and to modify the official information on products.

Antidepressants during pregnancy: a French drug utilisation study in EFEMERIS cohort.

BACKGROUND: Previous studies have suggested that exposure to some antidepressants (AD) during pregnancy could be associated with an increased risk of congenital malformations and neurodevelopment disorders for the child. We conducted a study to describe the use of AD during pregnancy in France. METHODS: We performed a drug utilisation study in EFEMERIS, a French cohort of pregnant women. At the time of the present study, 89,170 pregnant women, who were pregnant from 2005 to 2014 in Haute-Garonne were included. Prevalence and incidence of AD prescriptions during pregnancy, characteristics of AD users, and trends in AD use over the 10-year period were studied. RESULTS: During the 10-year study period, 1620 women registered in EFEMERIS (1.8%) received at least one prescription and dispensation for AD during pregnancy: 1363 during the first (1.5%), 591 during the second (0.7%), and 412 during the third (0.5%) trimester. A total of 2874 women (3.2%) got a prescription for an AD during the 3 months before and/or during pregnancy; 2187 of them (76.1%) stopped AD before pregnancy or during the first trimester. Selective serotonin reuptake inhibitors represented the most prescribed class during pregnancy (1.3%). A very slight decrease in the prevalence of AD prescriptions in pregnant women over time (1.7% in 2014 vs 2% in 2005) and some variations within classes were observed. CONCLUSIONS: Nearly, 2% of women received antidepressant drugs during pregnancy. This assessment encourages following research on these drugs including the potential risk of neurodevelopmental disorders in children after an exposure to antidepressants during pregnancy.

[Benzodiazepine use and misuse in France]. / Usages et mésusages des benzodiazépines en population en France.

Benzodiazepine use remains high in France in 2015, especially among the elders. However, encouraging trend is observed regarding hypnotic benzodiazepines initiation: between 2008 and 2015, incident use of hypnotics, including that of Z-drugs, decreased while incident use of anxiolytics remained stable. Most of new benzodiazepine users (86 %) had treatment duration that complies with guidelines. Owing to the high number of user initiating a treatment each year and associated risks, the remaining 14 % of long-term users is of concern. Roughly half of benzodiazepine users presented with comorbidities and concurrent medications increasing the risk of adverse drug reactions, especially central nervous system depressant effects.

Patterns of antidepressant use during pregnancy: a nationwide population-based cohort study.

AIMS: We explored the patterns of antidepressant use during pregnancy. METHODS: A cohort of women who started a pregnancy in 2014 was identified using data from the French reimbursement healthcare system (covering approximately 99% of the population). Antidepressant usage (initiated before or during pregnancy) was assessed. Explored changes in antidepressant treatment were: associations, switches, discontinuation and resumption of antidepressants during pregnancy. RESULTS: The cohort included 766 508 pregnancies (755 519 women). Antidepressant use during pregnancy was 25.7 per 1000 [95% CI: 25.3-26.0]. New use concerned 3.9 per 1000 [95% CI: 3.7-4.0]; the most initiated class during pregnancy was selective serotonin reuptake inhibitors (SSRIs), while the most prescribed individual drug in second and third trimesters was amitriptyline, a tricyclic. Most changes were observed before pregnancy and during the first trimester: 63% of ongoing treatments in the year before pregnancy were discontinued before conception; 68% of treatments maintained after conception were discontinued during the first trimester; switches or antidepressant associations mostly occurred during the periconceptional period or during the first trimester. Regardless of initial antidepressant, switches to sertraline were the most frequent. Associations mainly consisted of a prescription of tri-/tetracyclic or mirtazapine/mianserin in addition to an SSRI. Discontinuation during pregnancy led to treatment resumption in 22% of pregnancies. CONCLUSIONS: These results suggest that pregnancy was planned or the treatment especially adapted in accordance with existing recommendations in a large proportion of women under antidepressants or in whom such treatments have been initiated after starting a pregnancy.

Antipsychotics use: 2006-2013 trends in prevalence and incidence and characterization of users.

PURPOSE: The present study was conducted to describe antipsychotic (AP) prevalent and incident use, characteristics of AP users, and their trends in the French population. METHODS: A cross-sectional study was repeated yearly from January 1, 2007 to December 31, 2013 (for prevalence analysis) or to December 31, 2012 (for incidence analysis) using the French Health Insurance reimbursement database (Echantillon Généraliste de Bénéficiaires, EGB). For each year studied, prevalent and incident AP users were described in terms of age and gender overall, and according to the type of AP (FGAPs or SGAPs) used at index date. In addition, concurrent medications and comorbidities that a priori contraindicate the use of drugs having atropinic properties were researched. RESULTS: Prevalence and incidence remained relatively stable along the 2007-2013 period. Trends slightly decreased, from 2.07% (n = 10,252) to 2.05% (n = 11,015) for prevalence, and from 0.73% (n = 3461) to 0.66% (n = 3363) for incidence, especially in elderly, in contrast of children and adolescents (+ 39% for prevalence, from 184 to 271). The number of coprescribed drugs was found high (median = 5) and remained constant over time. In 2013, about 7% of prevalent AP users presented with a comorbidity increasing the risk of atropinic ADRs, and 36% used at least one concurrent atropinic drug. In incident AP users, these numbers were of 8 and 29%, respectively. CONCLUSIONS: The present study highlighted a marked shift from FGAPs toward SGAPs, as well as an increase in AP use in children and adolescents in France.

Prevalence and prescription patterns of oral glucocorticoids in adults: a retrospective cross-sectional and cohort analysis in France.

OBJECTIVES: To study trends in use of oral glucocorticoids (GCs) among adults, characteristics of oral GC initiators and prescriptions for the prevention of potential adverse effects associated with GC therapy. DESIGN: First, a cross-sectional study repeated yearly was performed from 2007 to 2014 in a nationwide representative sample. Second, characteristics of initiators and patterns of GC therapy during the year following treatment initiation were described in a cohort of patients who began GC between 2007 and 2013. SETTING: Population-based study using data from the French reimbursement healthcare system (covering approximately 90% of the population) in patients aged ≥18 years. RESULTS: Over the study period, the prevalence of oral GC use ranged from 14.7% to 17.1% (95% CI 17.0%-17.2%) with a significant increase of 14.1% (95% CI +13.5% to +14.8%). The 2007-2013 cohort of oral GC initiators comprised 206 759 individuals. Oral GC use was mostly short-term (68% of unique reimbursement) and more than half of short-term users took concurrent antibiotics or respiratory/otological drugs. Chronic users (≥6 reimbursements/year) represented 1.8% (n=3789) of the cohort. The proportion of chronic users with comorbidities likely to be worsened by GC use (diabetes, psychotic disorders, osteoporosis) was 25%. Among patients at increased risk of osteoporosis, 62% received specific prevention/monitoring measures and only 27% had a bisphosphonate. Half of chronic oral GC users had a concurrent reimbursement of a proton pump inhibitor in the absence of non-steroidal anti-inflammatory drug use. CONCLUSIONS: Oral GC use was highly widespread and increased among adults from 2007 to 2014. The overwhelming short-term use could mainly concern a growing use of unjustified prescriptions rather than situations with a favourable benefit/risk ratio. For chronic users, our findings plead for the development of interventions designed to improve monitoring with regard to the frequent comorbidities at risk and inappropriate prescribing of preventive therapeutic measures.

Road traffic crash risk associated with prescription of hydroxyzine and other sedating H1-antihistamines: A responsibility and case-crossover study.

BACKGROUND: H1 antihistamines differ from each other by their ability to cross the blood-brain barrier. The resulting sedating effect can be sought in therapy but may be a driving hazard. The aim of this study was to estimate the impact of sedating H1-antihistamines on the risk of road traffic crash, with a particular focus on hydroxyzine which is also indicated as an anxiolytic in France. METHODS: The study consisted in extracting and matching data from three French nationwide databases: the national healthcare insurance database, police reports and the police national database of injurious crashes. All sedating H1-antihistamines, including hydroxyzine, were considered in the study. A case-control analysis, in which responsible drivers were cases and non-responsible were controls was performed. A case-crossover analysis, comparing for the same subject exposure during a period immediately before the crash with exposure during an earlier period, was also conducted. RESULTS: The extraction and matching procedures over the July 2005-December 2011 period led to the inclusion of 142,771 drivers involved in an injurious road traffic crash. The responsibility study found an increased risk of being responsible for an injurious road traffic crash in hydroxyzine users who were registered with a long-term chronic disease (mostly psychiatric disorders) on the day of the crash (OR=1.67 [1.22-2.30]). Among them, the risk was even higher in drivers with highest exposure levels (OR=2.60 [1.23-5.50]). There was no impact of sedating H1 antihistamine treatment initiation on the risk of crash. CONCLUSION: Even if it is difficult to disentangle the part of the increased risk that would be causally related to hydroxyzine and the part related to behaviours of patients with a heavy psychiatric disorder, our study raises the alarm on the crash risk linked to hydroxyzine utilization in countries in which the anxiolytic indication is widespread.

Trends in incident use of benzodiazepines and Z-drugs in France from 2006 to 2012: a population-based study.

PURPOSE: To study trends in incident use of benzodiazepines in France between 2006 and 2012. METHODS: A cross-sectional study repeated yearly was conducted using data from the French national healthcare insurance system. New benzodiazepine users were defined as users without any benzodiazepine dispensing in the year prior to the first dispensing of benzodiazepine in each year. Relative changes in incidence of use were calculated with the year 2006 as reference; confidence intervals for changes were estimated using the bootstrap method. RESULTS: Over the study period, the incident use of benzodiazepines decreased from 6.2% to 5.9%; this corresponded to a 5.1% decrease (95%CI: -6.8% to -4.2%) for 2012 compared to 2006. The decrease mainly concerned hypnotics (-15.5%; -21.2% to -15.3%) and appeared more pronounced in people aged 18-44 years. Incident use of anxiolytics remained stable overall during the period (4.0% of the population). Within anxiolytics, incident use of long half-life benzodiazepines (bromazepam, prazepam) decreased in favor of short half-life benzodiazepines (alprazolam, oxazepam). This change concerned patients aged 65-79 and patients aged 80 years and over. Nevertheless, in 2012, nearly one third of incident users aged 65 years and over started a treatment with a long half-life benzodiazepine, mostly bromazepam. CONCLUSIONS: A limited decrease in incident benzodiazepine use was observed in France between 2006 and 2012 that concerned only hypnotics. Although congruent with recommendations, this improvement appears insufficient with regard to the level of exposure to these drugs in France. New actions especially targeting anxiolytic benzodiazepine use should be undertaken to consolidate these results. Copyright © 2016 John Wiley & Sons, Ltd.

Comorbidities and concurrent medications increasing the risk of adverse drug reactions: prevalence in French benzodiazepine users.

PURPOSE: To estimate benzodiazepine prevalence of use and to quantify, in benzodiazepine users, the prevalence of comorbidities and concurrent medications increasing the risk of adverse drug reactions (ADRs). METHODS: Cross-sectional study performed using data from the French national healthcare insurance system. The prevalence of use was estimated by considering as users, patients who had at least one benzodiazepine reimbursement during the year 2013. Patients at increased risk for benzodiazepine ADRs were those who had (i) drug-drug interactions at risk for central nervous system and respiratory depression and (ii) comorbidities at risk for adverse respiratory effects, or for falls or fractures. RESULTS: Overall, the prevalence of benzodiazepine use in 2013 was estimated to be 13.8 %; it was higher among women and increased with age. This prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at increased risk for benzodiazepine ADRs; this proportion increased with age. Drug-drug interactions represented the most prevalent condition (39.3 % of benzodiazepine users). The drugs most frequently involved were opioids: analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine users had comorbidities at increased risk for adverse respiratory effects (13.9 % in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or fractures (13.4 % in those aged ≥80). CONCLUSIONS: This study found that benzodiazepine use remained high in France, and that roughly half of the users presented with comorbidities and concurrent medications increasing the risk of ADRs. These findings are of concern, given that benzodiazepines are frequently used, and especially among the elderly.

Drug use in French children: a population-based study.

BACKGROUND AND OBJECTIVE: To provide an overview of drug use in outpatient children in France, a population-based study using a national reimbursement claims database representative of 90% of the French population was conducted. DESIGN: Cross-sectional study performed between January and December 2011 using the EGB database (Echantillon Généraliste de Bénéficiaires), a 1/97th sample of the national healthcare insurance system beneficiaries. Drug use in children <18 years old was estimated through reimbursements for prescribed drugs excluding vaccines. Prevalences of use were calculated for different levels of the Anatomical Therapeutic Chemical classification by considering as users children who had at least one reimbursement during the study period. RESULTS: In 2011, 133,800 children were included in the study. The overall prevalence of drug use was 84% and the median number of different drugs per child was 5. Drug use was greatest in children aged <2 years. The most widely used drugs were paracetamol, systemic anti-infectives, nasal corticosteroids and decongestants, and anti-histamines. 21% children <2 years received domperidone. CONCLUSIONS: There is widespread use of medicines that are unlikely to be effective and may have significant toxicity in French children. Irrational use of medicines appears to be greatest in children aged 5 years and under.

Incidence of hospital admissions due to adverse drug reactions in France: the EMIR study.

To assess the incidence of hospital admissions related to adverse drug reactions (ADRs) in France and the frequency of preventable ADRs in France, a prospective study was conducted among a representative randomly selected sample of medical wards in public hospitals between December 2006 and June 2007; all patients admitted during a 2-week period were included. An ADR-related hospitalization case was defined as a hospital admission because of an ADR, and an independent committee reviewed and validated all potential cases. Preventability was assessed using the French ADR preventability scale. Data were extrapolated to the population of France. Among 2692 admissions, 97 were related to an ADR (incidence 3.6%, 95% confidence interval, CI [2.8-4.4]). Patients admitted for an ADR were significantly older than those admitted for other reasons (P < 0.001). A third (32.0%) of ADR-related hospitalizations were 'preventable', 16.5% 'potentially preventable'. Drug interactions accounted for 29.9% of ADR-related hospitalizations. The most frequent causes of ADR-related hospitalizations were vascular disorders (20.6%), mainly bleeding complications, central nervous system disorders (11.3%), gastrointestinal disorders, and general disorders (9.3%). Antithrombotic and antineoplastic agents were the most frequently involved (12.6% each), followed by diuretics and analgesics (9.0% each). Vitamin-K-antagonists (VKAs) were the most common drugs associated with admission. The estimated annual number of ADR-related hospitalizations in France was 143 915 (95% CI [112 063-175 766]). ADRs were a significant cause of hospital admission in 2006-2007, in particular those due to VKAs. As new oral anticoagulants (NOACs) have been marketed, more attention needs to be paid to ensure a safe use of antithrombotic agents.

Cutaneous adverse effects of ketoprofen for topical use: clinical patterns and costs.

BACKGROUND: Since its introduction in France, ketoprofen for topical use has been associated with a large number of cutaneous adverse effect reports. Therefore, the French Medicine Agency progressively introduced warnings and contraindications to its use. Despite this, serious adverse drug reactions (ADRs) still occur. OBJECTIVE: To describe clinical patterns and estimate costs of spontaneously reported cutaneous ADRs of topical ketoprofen. METHODS: All cases of cutaneous ADRs of topical ketoprofen reported to the Bordeaux regional pharmacovigilance center between January 1989 and December 2006 were included. Clinical patterns, in respect of adherence to recommendations, causality, seriousness, and direct costs incurred by the ADRs, were assessed. RESULTS: A total of 136 cases were reported (median age: 42 years, 55.9% women). Proper use of topical ketoprofen regarding indications, warnings, and contraindications was not respected by one-third of the patients. Almost all cases occurred during sunny months. Symptoms consisted predominantly of bullous eruptions (29.4%) or contact dermatitis (27.2%). Generalized lesions were observed in 37.5% of patients. Causality was considered at least possible for most of the cases (92.6%). These ADRs induced hospital admission in 15 cases (11.0%). The total estimated cost was euro 42,962 ($US 66,559), corresponding to euro 316 per case. This mean cost was nine times higher for serious ADRs. CONCLUSION: Topical ketoprofen is used to treat benign symptoms but can be associated with serious and costly cutaneous ADRs. Furthermore, the number of cases and the calculated costs may have been greatly under-estimated in the present study.