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AIM: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe mostly drug-induced cutaneous reactions. Acetaminophen is an over-the-counter drug used worldwide to treat pain and reduce fever. In 2013, the US Food and Drug Administration informed the public that acetaminophen was associated with a rare risk of SJS/TEN. The aim of the present retrospective study was to analyse reports of acetaminophen as a possible suspect in the development of SJS/TEN from the French Pharmacovigilance Database (FPDB). METHODS: Cases of TEN/SJS with acetaminophen as a suspect drug registered in the FPDB, collected from January 2002 to December 2013, were analysed by an expert group. The algorithm of drug causality for epidermal necrolysis (ALDEN) was used as a reference tool for SJS/TEN to assess the causality of each suspect drug. RESULTS: After exclusion of 16 nonvalidated cases, 112 cases (47 TEN, 51 SJS, 14 SJS/TEN overlaps) involving 574 suspected drugs (5â 1/case) were analysed. In 80 cases, the acetaminophen ALDEN score was inferior or equal to that of other drugs, associated with a higher suspicion for causality. In 32 cases, acetaminophen had the highest score but matched with a 'very unlikely' or 'unlikely' causality in 12 cases. For the 20 remaining cases with a 'possible' or ' probable' causality, a protopathic or a confounding bias was likely in 14 cases. CONCLUSIONS: After analysis of the French pharmacovigilance data using the ALDEN algorithm, we found no obvious SJS/TEN risk related to the use of acetaminophen in this large national series.
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Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Síndrome de Stevens-Johnson/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos , Risco , Síndrome de Stevens-Johnson/etiologia , Adulto JovemRESUMO
PURPOSE: Most drugs are excreted in maternal milk and may therefore be ingested by children during breastfeeding. Data concerning the safety of the use of drugs by breastfeeding women are patchy, and almost nothing is known about this issue for many drugs. METHODS: The aim of this study was to describe the adverse drug reactions of drugs transmitted in breast milk on the basis of the data collected in the French Pharmacovigilance Database. All spontaneous reports of adverse drug reactions (ADRs) in breastfed infants recorded in the National Pharmacovigilance Database by the 31 French regional pharmacovigilance centres between 1984 and June 2011 were investigated. RESULTS: Between January 1985 and June 2011, 276 adverse drug reactions in 174 breastfed children were notified to the French Pharmacovigilance Network. The most frequently reported adverse drug reactions were neurological (28.6 %) and gastrointestinal (20.3 %). Sixty-five of the adverse drug reactions recorded were considered to be serious (37.4 %). The results of our study confirm that certain drugs were frequently implicated in serious adverse drug reactions. Two cases of ADRs (1.1 %) had a 'certain' causality score (I4) and 13 (7.5 %) a 'likely' score (I3). The suspected drugs include antiepileptic drugs, opiate analgesics and benzodiazepines. These results also demonstrate that some drugs that were thought to be anodyne or for which no data were available, such as ketoprofen and hydroxyzine, may be implicated in adverse effects. Finally, these data show that certain drugs, like pseudoephedrine, which should not be used during breastfeeding, were nevertheless implicated in several of the adverse drug reactions recorded. CONCLUSION: This study shows that ADR via breastfeeding are rarely reported due to low awareness or low occurrence of ADR via breast milk. These results highlight the need for additional pharmacokinetic, clinical and epidemiological studies, given the paucity of published data. They also demonstrate the need to improve information for the general public about drugs and self-medication during breastfeeding.
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Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Aleitamento Materno/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/efeitos adversos , Pré-Escolar , Feminino , França , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , FarmacovigilânciaRESUMO
To contribute to the development of sustainable composites, this work investigates the effects of moisture on the key AE characteristics related to the damage mechanisms of a bio-based balsa wood core sandwich in 4-point bending tests, including cumulative counts, amplitude, peak frequency, and duration. Novel triple dog-bone balsa wood core sandwich specimens with different MC (moisture content) were studied by comparing microscopic observations and a proposed two-step clustering approach in AE analysis. Three MC states, i.e., dry, 50% MC, and 120% MC, are discussed. GFRP (glass-fiber-reinforced polymer) laminate skin damages were found to be predominant in most GFRP-balsa sandwich specimens, but balsa wood core damages play a more important role as MC increases. The degradation of the bending stiffness of the sandwich was proven to be faster in the first linear stage of the moisture absorption curve, while the decrease in bending strength was more pronounced at the MC saturation level. Finally, for all of the dry and wet sandwich specimens, peak frequency and duration were proven to be more helpful in identifying damages associated with the lighter bio-based balsa wood core, such as balsa core damages and skin/core debonding.
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PURPOSE: To assess the prevalence of adverse drug reactions (ADRs) occurring in patients with Alzheimer's disease (AD) or other dementia in France. METHODS: A cross-sectional multicentre study was conducted by the French network of the 31 regional pharmacovigilance centres on a given day. The subjects were selected by random draw to be a representative sample of French patients with dementia: consultations of dementia clinics, nursing-homes, acute and long care geriatric units, rehabilitation care geriatric units. The staff of each medical structure together with that of the pharmacovigilance centre defined a day for including the patients. Socio-demographic data, history, ADR and drugs given were registered. RESULTS: There were 1332 subjects included, 51.1% living at home, 48.8% in institutions, aged 82.0 ± 8.0 years (46-108); 61.3% suffered from AD. Mean number of drugs was 6.3 ± 3.1. Anti-dementia drugs were given to 66.4% subjects. ADR prevalence was 5.0% (95% CI: 3.9-6.2) without a significant difference between at home and institutionalized patients. ADR consisted of gastro-intestinal (23.2%), central nervous system (17.4%) and psychiatric disorders (8.7%). Of the ADR, 31.9% were serious, and 47.8% preventable. The drugs most often involved were anti-dementia (28.9%), cardio-vascular (28.9%) and psychotropic drugs (26.4%, anxiolytics, hypnotics, antidepressants, neuroleptics). CONCLUSION: This national scale study showed that iatrogenesis in patients with AD and related dementia can at times be serious and preventable. Therefore, special attention is required when prescribing psychotropic and anti-dementia drugs, as they are frequently used and induce half of the ADR in this population.
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Doença de Alzheimer/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Farmacovigilância , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Estudos Transversais , Demência/complicações , Demência/tratamento farmacológico , Demência/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , França/epidemiologia , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores SocioeconômicosRESUMO
Red yeast rice (RYR) is a dietary supplement containing monacolins obtained by fermentation of Monascus purpureus strains. Because of its structural homology with lovastatin, monacolin K inhibits HMG-CoA reductase and shows hypocholesterolemic properties comparable to synthetic statins. We studied all cases of myopathy involving RYR reported in the French national pharmacovigilance database (6 cases) and in scientific literature (9 cases). Among these cases, 9 showed elevated creatine kinase, 3 rhabdomyolysis and 2 myalgia. Recent studies seem to show good efficacy of the RYR, however, our work reports the existence of related muscular disorders. In addition, dietary supplements currently available on the market may show considerable variability of formulation and/or the presence of contaminants. When clinicobiological disorders occur, physicians should consider the eventual use of an herbal treatment.
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Non-viral gene delivery into the liver generally mediates a transient transgene expression. A comparative analysis was performed using two gene vectors, pFAR4 and pKAR4, which differ by the absence or presence of an antibiotic resistance marker, respectively. Both plasmids carried the same eukaryotic expression cassette composed of a sulfamidase (Sgsh) cDNA expressed from the human alpha antitrypsin liver-specific promoter. Hydrodynamic injection of the pFAR4 construct resulted in prolonged sulfamidase secretion from the liver, whereas delivery of the pKAR4 construct led to a sharp decrease in circulating enzyme. After induction of hepatocyte division, a rapid decline of sulfamidase expression occurred, indicating that the pFAR4 derivative was mostly episomal. Quantification analyses revealed that both plasmids were present at similar copy numbers, whereas Sgsh transcript levels remained high only in mice infused with the pFAR4 construct. Using a chromatin immunoprecipitation assay, it was established that the 5' end of the expression cassette carried by pKAR4 exhibited a 7.9-fold higher heterochromatin-to-euchromatin ratio than the pFAR4 construct, whereas a bisulfite treatment did not highlight any obvious differences in the methylation status of the two plasmids. Thus, by preventing transgene expression silencing, the pFAR4 gene vector allows a sustained transgene product secretion from the liver.
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OBJECTIVE: To evaluate in real conditions the role of drugs in heat-related adverse effects. METHODS: We performed a multicentric case-control study in 3 university hospitals in France, including 36 cases (patients older than 65 years hospitalized with hyperthermia or dehydration between 1st July and 31st August 2007) and 51 controls. We compared drugs and changes in drug dosage according to the values of renal function. RESULTS: At inclusion, clearance creatinine was available for only 12 patients (mean = 31.6 ml/min), and three-fold higher in controls (p < 0.001). Cases took more drugs than controls (4.3 vs. 3.9; p < 0.001), particularly neuroleptic drugs (3.6% vs. 0.5%; p = 0.007). CONCLUSION: Despite its small size, our study shows that patients suffering from dehydration in summer are those with more severe renal impairment, taking more drugs (particularly neuroleptics). This pilot work could allow to improve methodology of further studies on drugs during heat waves.
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Desidratação/tratamento farmacológico , Tratamento Farmacológico , Febre/tratamento farmacológico , Temperatura Alta/efeitos adversos , Tempo (Meteorologia) , Idoso , Estudos de Casos e Controles , Feminino , França , Humanos , MasculinoRESUMO
The anti-angiogenic and neurogenic pigment epithelium-derived factor (PEDF) demonstrated a potency to control choroidal neovascularization in age-related macular degeneration (AMD) patients. The goal of the present study was the development of an efficient and safe technique to integrate, ex vivo, the PEDF gene into retinal pigment epithelial (RPE) cells for later transplantation to the subretinal space of AMD patients to allow continuous PEDF secretion in the vicinity of the affected macula. Because successful gene therapy approaches require efficient gene delivery and stable gene expression, we used the antibiotic-free pFAR4 mini-plasmid vector to deliver the hyperactive Sleeping Beauty transposon system, which mediates transgene integration into the genome of host cells. In an initial study, lipofection-mediated co-transfection of HeLa cells with the SB100X transposase gene and a reporter marker delivered by pFAR4 showed a 2-fold higher level of genetically modified cells than when using the pT2 vectors. Similarly, with the pFAR4 constructs, electroporation-mediated transfection of primary human RPE cells led to 2.4-fold higher secretion of recombinant PEDF protein, which was still maintained 8 months after transfection. Thus, our results show that the pFAR4 plasmid is a superior vector for the delivery and integration of transgenes into eukaryotic cells.
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Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal blood vessels growing into the subretinal space, leading to retinal pigment epithelial (RPE) cell degeneration and vision loss. Vessel growth results from an imbalance of pro-angiogenic (e.g., vascular endothelial growth factor [VEGF]) and anti-angiogenic factors (e.g., pigment epithelium-derived factor [PEDF]). Current treatment using intravitreal injections of anti-VEGF antibodies improves vision in about 30% of patients but may be accompanied by side effects and non-compliance. To avoid the difficulties posed by frequent intravitreal injections, we have proposed the transplantation of pigment epithelial cells modified to overexpress human PEDF. Stable transgene integration and expression is ensured by the hyperactive Sleeping Beauty transposon system delivered by pFAR4 miniplasmids, which have a backbone free of antibiotic resistance markers. We demonstrated efficient expression of the PEDF gene and an optimized PEDF cDNA sequence in as few as 5 × 103 primary cells. At 3 weeks post-transfection, PEDF secretion was significantly elevated and long-term follow-up indicated a more stable secretion by cells transfected with the optimized PEDF transgene. Analysis of transgene insertion sites in human RPE cells showed an almost random genomic distribution. The results represent an important contribution toward a clinical trial aiming at a non-viral gene therapy of nvAMD.
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The ability of the gut hormone ghrelin to promote positive energy balance is mediated by the growth hormone secretagogue receptor (GHSR). GHSR is a G protein-coupled receptor (GPCR) that is found centrally and peripherally and that can signal in a ligand-independent manner basally or when heterodimerized with other GPCRs. However, current Ghsr knockout models cannot dissect ghrelin-dependent and ghrelin-independent signaling, precluding assessment of the physiological importance of these signaling pathways. An animal model carrying a Ghsr mutation that preserves GHSR cell surface abundance, but selectively alters GHSR signaling, would be a useful tool to decipher GHSR signaling in vivo. We used rats with the Ghsr(Q343X) mutation (Ghsr(M/M)), which is predicted to delete the distal part of the GHSR carboxyl-terminal tail, a domain critical for the signal termination processes of receptor internalization and ß-arrestin recruitment. In cells, the GHSR-Q343X mutant showed enhanced ligand-induced G protein-dependent signaling and blunted activity of processes involved in GPCR signal termination. Ghsr(M/M)rats displayed enhanced responses to submaximal doses of ghrelin or GHSR agonist. Moreover, Ghsr(M/M)rats had a more stable body weight under caloric restriction, a condition that increases endogenous ghrelin tone, whereas under standard housing conditions,Ghsr(M/M)rats showed increased body weight and adiposity and reduced glucose tolerance. Overall, our data stress the physiological role of the distal domain of GHSR carboxyl terminus as a suppressor of ghrelin sensitivity, and we propose using the Ghsr(M/M)rat as a physiological model of gain of function in Ghsr to identify treatments for obesity-related conditions.
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Adiposidade/efeitos dos fármacos , Apetite/efeitos dos fármacos , Grelina/farmacologia , Mutação , Receptores de Grelina/genética , Adiposidade/genética , Administração Intravenosa , Animais , Apetite/genética , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Restrição Calórica , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/genética , Feminino , Grelina/administração & dosagem , Grelina/metabolismo , Teste de Tolerância a Glucose , Hormônio do Crescimento/metabolismo , Células HEK293 , Humanos , Masculino , Microscopia Confocal , Oligopeptídeos/farmacologia , Ratos , Receptores de Grelina/agonistas , Receptores de Grelina/metabolismo , Transdução de Sinais/genética , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismoRESUMO
Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions. The objectives were to examine recent data on etifoxine-related ADR by reviewing Individual Case Safety Reports (ICSRs) recorded in France especially unexpected ADRs. Etifoxine-related ICSRs were extracted from the French Pharmacovigilance database from 1 January 2000 to 30 April 2012 and data from the marketing authorization holder up to 31 December 2011 were also obtained. Of the 350 cases retained for analysis, 123 (35%) were considered serious. Dermatological or acute hypersensitivity reactions were the most frequent ADRs (59%) mainly isolated cutaneous eruptions. However, there were 24 cases of severe toxidermia (DRESS in 5, erythema multiforme in 10 and Stevens-Johnson syndrome in 5) with etifoxine as the most suspected drug in 11 patients, and seven cases of vasculitis or serum sickness-like reaction. Liver disorders were reported in 34 patients of whom 25 developed acute hepatitis with a cytolytic biological pattern in 16. Other unexpected ADRs included 16 reversible cases of metrorrhagia with positive rechallenge in 5, and three cases of biopsy-proven microscopic colitis of which one recurred after etifoxine re-administration. Although etifoxine has been marketed for more than 30 years, this survey identified a number of unexpected and sometimes serious ADRs, in particularly severe toxidermia and acute cytolytic hepatitis. A recent update of the French etifoxine summary of the product characteristics (SPC) was based on these findings.
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Oxazinas/efeitos adversos , Farmacovigilância , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Criança , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
To report three cases of bullous pemphigoid in patients treated with vildagliptin. Case 1: An 86-year-old woman presented with bullous pemphigoid after 1 month of treatment with vildagliptin and metformin. After introduction of clobetasol, the symptoms resolved although vildagliptin was continued. However, the skin lesions reappeared 3 months later. Sustained remission was achieved only after definitive withdrawal of vildagliptin. Case 2: A 79-year-old man presented with bullous pemphigoid after 37-month treatment with gliclazide, vildagliptin and metformin. The disease at first responded to clobetasol but 3 months later the lesions reappeared. They finally regressed when the gliptin was discontinued. Case 3: A 77-year-old woman, treated with gliclazide and vildagliptin for 26 months, presented with bullous pemphigoid, which responded well to discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules for treatment of type 2 diabetes mellitus, which have been suspected of implication in bullous pemphigoid. Such cases have been described in the literature (seven with vildagliptin and three with sitagliptin). In nine of these cases, the gliptin was associated with metformin, but the latter had never been considered responsible. The mechanism implicated in the development of bullous pemphigoid has not yet been clearly identified, but may involve a modified immune response or alteration of the antigenic properties of the epidermal basement membrane. These reports support the risk of bullous pemphigoid in patients exposed to gliptins.
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Adamantano/análogos & derivados , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Nitrilas/efeitos adversos , Penfigoide Bolhoso/induzido quimicamente , Pirrolidinas/efeitos adversos , Adamantano/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , VildagliptinaRESUMO
OBJECTIVE: To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. DESIGN: The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. SETTING: Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. PATIENTS: The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. RESULTS: The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (nâ=â27), worsening of respiratory distress during respiratory tract infection (nâ=â35), dyspnoea (nâ=â18), cough aggravation or prolongation (nâ=â11), and bronchospasm (nâ=â1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. CONCLUSION: Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.
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Acetilcisteína/efeitos adversos , Carbocisteína/efeitos adversos , Expectorantes/efeitos adversos , Inquéritos Epidemiológicos , Doenças Respiratórias/tratamento farmacológico , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Lactente , MasculinoAssuntos
Apendicite/complicações , Buprenorfina/efeitos adversos , Erros de Diagnóstico , Hipestesia/induzido quimicamente , Perfuração Intestinal/complicações , Antagonistas de Entorpecentes/efeitos adversos , Peritonite/diagnóstico , Abscesso/complicações , Adulto , Analgésicos Opioides/efeitos adversos , Apendicite/diagnóstico , Buprenorfina/uso terapêutico , Humanos , Perfuração Intestinal/diagnóstico , Masculino , Antagonistas de Entorpecentes/uso terapêutico , Peritonite/etiologia , Prisioneiros , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/tratamento farmacológicoRESUMO
PURPOSE: This study proposes to complete declarative studies by describing the prescriptions of anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002. METHODS: This cross-sectional study analyzes all the hypnotic, anxiolytic, and antidepressant prescriptions (ATC codes beginning with N05B, N05C, and N06A, respectively) sent by adolescents (aged 13-17 years) to the French Health Insurance system of the study region for reimbursement during one year (2002). It was performed in a southern France area with 120,908 adolescents covered by this insurance scheme. Adverse drug reactions (ADRs) recorded in the Pharmacovigilance database were also studied. RESULTS: Three thousand two hundred and eighty-six adolescents (2.7% of adolescent population) had at least one prescription of the studied drugs. This prevalence increased with age and female sex, leading to a maximum of 6.3% for the 17-year-old girls. Two thousand four hundred and thirty-one of adolescents were dispensed anxiolytics, 935 antidepressants, and 548 hypnotics. The most dispensed drugs were zolpidem, zopiclone, and niaprazine for hypnotics; hydroxyzine, etifoxine, and bromazepam for anxiolytics; and paroxetine, sertraline, and fluoxetine for antidepressants. Zolpidem, hydroxyzine, and paroxetine accounted, respectively, for 82.9%, 57.1%, and 59.8% of the prescriptions. 75.5% of hypnotics users had only one prescription, 77.4% for anxiolytics, and 57.4% for antidepressants. Three ADRs were reported. CONCLUSIONS: This study confirms the large use of psychotropics in French adolescents and the influence of age and sex. Also, the results underline treatment for most adolescents is short, which may be beneficial for hypnotics and anxiolytics but not for antidepressants.
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Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Adolescente , Sistemas de Notificação de Reações Adversas a Medicamentos , Ansiolíticos/efeitos adversos , Antidepressivos/efeitos adversos , Estudos Transversais , Prescrições de Medicamentos , Uso de Medicamentos , Feminino , França , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Estações do Ano , Fatores de TempoRESUMO
BACKGROUND: Zoledronic acid-associated renal impairment leading to renal failure has been recently reported in a cohort of US patients. However, the presence of such toxicity in other populations has not yet been determined. OBJECTIVE: To analyze French cases of zoledronic acid-associated nephrotoxicity. METHODS: We evaluated available cases with acute deterioration of renal function associated with zoledronic acid therapy drawn from the French Adverse Event Reporting System database until July 1, 2004. RESULTS: We identified 4 men and 3 women between the ages of 52 and 70 years, with multiple myeloma or different types of metastatic cancer, who had experienced renal impairment during zoledronic acid therapy. Four patients developed de novo acute renal failure, while the other 3 patients experienced acute deterioration of preexisting chronic renal failure. Renal failure occurred after various durations of zoledronic acid therapy (1-120 days). Three patients completely recovered and one partially recovered their previous renal function after discontinuation of zoledronic acid, but renal impairment was associated with a fatal outcome in 2 cases; the outcome of the other case was unknown. Our data confirm the previously reported risk factors for zoledronic acid-associated nephrotoxicity such as advanced cancer, multiple myeloma, preexisting renal failure, diabetes, hypertension, and concomitant use of nephrotoxic drugs. CONCLUSIONS: These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.