RESUMEN
Paraphenylenediamine is an aromatic amine used as a hair dye; it is responsible for poisoning characterized by respiratory distress involving life-threatening. The objective of this work is the development and validation of an assay of para-phenylenediamine in the whole blood. The method is based on the determination of paraphenylene diamine in whole blood by gas chromatography-mass spectrometry after liquid-liquid extraction and derivatization. The validation protocol has included the study of the recovery factor of extraction, the measurement range, accurency, repetability and intermediate precision. The calibration curve was linear between 98 and 1350 µg/L (r = 0.999), the limit of detection and quantification were 37 µg/L and 63 µg/L respectively. The accuracy were 94.7%. Coefficients of variation were (2.3/6.8/9.7%) for repeatability and (4.4/8.7/9.8%) for intermediate precision. The method is suitable for quantification of PPD in acute poisoning situations. A method for the determination of the paraphenylene diamine in the whole blood by gas chromatography coupled to mass spectrometry was developed. The validation of the method showed good linearity, good accuracy and low limit of quantification.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Tinturas para el Cabello/metabolismo , Fenilendiaminas/sangre , Calibración , Colorantes/metabolismo , Cromatografía de Gases y Espectrometría de Masas/métodos , Tinturas para el Cabello/envenenamiento , Humanos , Extracción Líquido-Líquido/métodos , Fenilendiaminas/envenenamiento , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
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.
Asunto(s)
Antidepresivos de Segunda Generación/efectos adversos , Bupropión/efectos adversos , Cese del Hábito de Fumar , Adolescente , Adulto , Anciano , Angioedema/inducido químicamente , Angioedema/epidemiología , Antidepresivos de Segunda Generación/uso terapéutico , Bupropión/uso terapéutico , Trastornos Cerebrovasculares/inducido químicamente , Trastornos Cerebrovasculares/epidemiología , Bases de Datos Factuales , Muerte Súbita Cardíaca/epidemiología , Erupciones por Medicamentos/epidemiología , Sobredosis de Droga/epidemiología , Femenino , Francia/epidemiología , Humanos , Masculino , Trastornos Mentales/inducido químicamente , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Persona de Mediana Edad , Isquemia Miocárdica/inducido químicamente , Isquemia Miocárdica/epidemiología , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/epidemiología , Vigilancia de Productos Comercializados , Factores de Riesgo , Convulsiones/inducido químicamente , Convulsiones/epidemiología , Enfermedad del Suero/inducido químicamente , Enfermedad del Suero/epidemiología , Suicidio/estadística & datos numéricos , Intento de Suicidio/estadística & datos numéricos , Adulto JovenAsunto(s)
Bloqueadores de los Canales de Calcio/efectos adversos , Enfermedades del Esófago/inducido químicamente , Morfolinas/efectos adversos , Bloqueadores de los Canales de Calcio/química , Medicamentos Genéricos/efectos adversos , Enfermedades del Esófago/patología , Humanos , Morfolinas/química , Úlcera/inducido químicamente , Úlcera/patologíaRESUMEN
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.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Renales/inducido químicamente , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Niño , Recolección de Datos , Femenino , Francia/epidemiología , Humanos , Recién Nacido , Enfermedades Renales/diagnóstico , Enfermedades Renales/patología , MasculinoRESUMEN
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.
RESUMEN
The HIMAGE study, conducted in partnership with the principal Public Health Insurance Funds of the Loire region, analysed medicinal prescriptions during pregnancy on the basis of a representative sample of 911 pregnant women resident in this region of France. Altogether 93.5% received at least one prescription, with a mean of 10.9 different drugs per woman. The prescriptions were predominantly for drugs of the following Anatomical Therapeutic Chemical (ATC) classes: "alimentary tract and metabolism" (78%); "genito-urinary system and sex hormones" (62%); "nervous system" (62%); and "blood and blood-forming organs" (57%). Iron supplements, paracetamol, folic acid, magnesium, progesterone, oxaceprol, phloroglucinol, amoxicillin, domperidone and diosmine were the most frequently prescribed drugs. In total, 4.6% of the women were exposed to drugs involving a risk during pregnancy: principally nonsteroidal anti-inflammatory drugs (NSAIDs) prescribed from the sixth month onwards. This study revealed a high frequency of prescription of drugs to pregnant women, largely motivated by non-rational and to some extent culture-specific considerations, and it also highlighted the prescription of drugs known to involve risk during pregnancy. These results provide a basis for advising clinicians on the rational and safe use of drugs during pregnancy.
Asunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Embarazo , Adulto , Utilización de Medicamentos , Femenino , Francia , HumanosRESUMEN
BACKGROUND: A possible association between low-molecular-weight heparins (LMWHs) and thrombocytosis was suspected from spontaneous reports to the French Pharmacovigilance System. This association is not mentioned in LMWH's summary of product characteristics. METHODS: All case records in the French Pharmacovigilance database were reanalyzed for relevance and causality, and the case/noncase approach was used including reports of thrombocytosis as cases and all other reports as noncases. RESULTS: Fifty-one patients treated with LMWHs had platelet counts >500 x 10(3)/mm(3). All patients were asymptomatic, and 1 had a positive rechallenge. There were 143 cases of thrombocytosis among the 174 213 reports in the database, with 61 of 4644 involving LMWHs. The calculated relative reporting ratio is 27.5 (p < 0.0001; 95% CI 19.5 to 38.9). CONCLUSIONS: There is a highly significant association of thrombocytosis reported with LMWH treatment.