Lamiae Bensouda-Grimaldi

Avoidability of Adverse Drug Reactions Spontaneously Reported to a French Regional Drug Monitoring Centre

AbstractBackground: Adverse drug reactions (ADRs) are now recognized as a major category of iatrogenic illness in terms of morbidity and mortality. Objective: To describe the type and frequency of avoidable ADRs spontaneously reported to a regional drug monitoring centre following inappropriate prescribing, as a basis for preventive actions.n Methods: A prospective, observational study of ADRs reported to the Regional Drug Monitoring Centre of Tours, France, between 26 November 2002 and 28 November 2003. The outcome measure was ADRs secondary to inappropriate prescribing that were defined as entirely or partly avoidable, i.e. at least one of the recommendations in various sections of the summary of product characteristics (SPC; indication, route of administration, dose, duration of treatment, dose adaptation, precautions for use, monitoring of treatment, absolute contraindications and contraindicated interactions) had not been respected. The link between the lack of conformity of the drug prescription with the SPC and occurrence of the ADR was evaluated by a working group using two criteria: (i) is nonconformity of the prescription of this drug a known and validated risk factor for this ADR?; and (ii) are there other aetiologies or other risk factors for this ADR?n Results: Three hundred and sixty ADRs in 294 adults and 66 children were analysed. The prescription was considered inappropriate for 213 of the 659 (32%) drugs implicated in ADRs, corresponding to 161 patients (45%). The ADR was adjudged entirely avoidable for 32 (9%) patients, partly avoidable for 28 (8%) patients and unavoidable for 300 (83%) patients. Not taking into account a history of allergy or altered renal function and not respecting the recommended dose were the most frequent causes of entirely avoidable ADRs. Allopurinol and lamotrigine were the drugs most frequently involved in serious avoidable ADRs.n Conclusions: Preventive actions should focus on more systematic allergy checks when prescribing drugs and on dose adaptation in cases of altered renal function.

L'enfant et les médicaments : application à la prescription en pédiatrie

Because of a lack in drug evaluation in children, they receive many off license drugs prescription, which means drugs prescribed in an indication, dosage, formulation or age different from the license terms. However, drug evaluation is crucial in paediatrics population because of pharmacokinetics and pharmacodynamics modifications throughout organism development, which make usually wrong any extrapolation to children of data obtained in adults. Drug safety is generally better in infants except in newborns who are at a particularly high drug-related risk because of high frequency of off license drug use, many drugs association and drugs metabolism immaturity. The lack of evaluation in children, the fact that children are the unique target population of some drugs or the maturation phenomena explain some adverse effects more specific in children. The more the children are young, the more they are exposed to medication or drug utilization errors. Physician must take what the SPC, as found in the Vidal® dictionary, mentions about children into account while prescribing. Drugs with a paediatric license must be preferred overall, however it should be kept in mind that a paediatric license means only that the drug is active in the indication of the license but it doesnt position it regarding other therapeutic alternatives. Off labeling prescription should be based on a supposed benefit, which had to be justified if a severe side effect occurred.

Drug dependence associated with triptans and ergot derivatives: a case/non-case study

IntroductionThe aim of this case/non-case study was to assess and compare the risk of drug dependence associated with different migraine-specific drugs, i.e., ergot derivatives and triptans, using the French pharmacovigilance database.MethodsReports on drug side effects recorded in this database between January 1985 and June 2007 were analyzed, and triptans (almotriptan, eletriptan, naratriptan, sumatriptan, and zolmitriptan) as well as ergot derivatives used in acute migraine were examined. For all reports, cases were defined as those reports corresponding to “drug abuse,” “physical or mental drug dependence,” and “pharmacodependence,” whereas “non-cases” were defined as all the remaining SED reports. The method’s reliability was assessed by calculating the risk associated with a negative (amoxicillin) and a positive (benzodiazepines) control. The risk of dependence associated with each drug and control was evaluated by calculating the odds ratio (OR) with a confidence interval of 95%.ResultsAmong the 309,178 reports recorded in the database, drug dependence accounted for 0.8% (2,489) of the reports, with 10.9% (449) involving a triptan, and 9.33% (332) an ergot derivative. The risk of dependence was similar for triptans and ergot derivatives and did not differ from that of benzodiazepines. In the triptan group, the risk (odds ratio [95% CI]) ranged from 10.3 [4.8–22.3] for sumatriptan to 21.5 for eletriptan [10.1–45.6], while in the ergot derivative group, it ranged from 12 [8–17.9] for ergotamine to 20.6 [8–53] for dihydroergotamine.ConclusionsThese findings confirm the hypothesis that triptans and ergot derivatives are associated with an increased risk of drug dependence.

Mise au pointL'enfant et les médicaments : application à la prescription en pédiatriePrescription in children

Because of a lack in drug evaluation in children, they receive many off license drugs prescription, which means drugs prescribed in an indication, dosage, formulation or age different from the license terms. However, drug evaluation is crucial in paediatrics population because of pharmacokinetics and pharmacodynamics modifications throughout organism development, which make usually wrong any extrapolation to children of data obtained in adults. Drug safety is generally better in infants except in newborns who are at a particularly high drug-related risk because of high frequency of off license drug use, many drugs association and drugs metabolism immaturity. The lack of evaluation in children, the fact that children are the unique target population of some drugs or the maturation phenomena explain some adverse effects more specific in children. The more the children are young, the more they are exposed to medication or drug utilization errors. Physician must take what the SPC, as found in the Vidal® dictionary, mentions about children into account while prescribing. Drugs with a paediatric license must be preferred overall, however it should be kept in mind that a paediatric license means only that the drug is active in the indication of the license but it doesnt position it regarding other therapeutic alternatives. Off labeling prescription should be based on a supposed benefit, which had to be justified if a severe side effect occurred.

Prescription of drugs contraindicated in children: a national community survey

Many drugs are prescribed off-label, which means outside the terms of the summary of product characteristics (SPC) i.e. indication, dosage, contraindication, etc, in children. Among the numerous studies about off-label use, no data have focused on drug use despite contraindication in children. The aim of this survey was to assess the frequency of prescription despite a contraindication for age in France. Drugs were defined as contraindicated for age if the SPC (as quoted in the French compendium Le Dictionnaire Vidal), indicated clearly that the drug is contraindicated in the age group of the patient receiving the prescription [1]. For each drug contraindicated, the reason given in the SPC for the contraindication for age was classified as “toxic effects described in children”, “insufficient data for use in children”, “unsuitable dosage strength or formulation for the age” or no explanation given. Moreover, to investigate avoidability of a contraindication transgression we searched for an available alternative defined as a product with the same active substance, the same route of administration but in a dosage licensed for children. The study population was children younger than 16 years, affiliated to the French mandatory national health fund (Caisse Nationale d’Assurance Maladie), refunded for prescriptions from office-based practice over 2 months. The use of this database did not need parents’ consent or ethics committee agreement. A total of 276,472 prescriptions including 1,068,705 drugs were refunded for children younger than 16 years. Of these, 11,138 prescriptions (4%) included at least one drug contraindicated for age i.e. 12,333 drugs contraindicated for age (1.2%). This percentage of contraindicated drugs is slightly higher than that found in two other studies (0.9% [7] 0.04% [5]), but the aim of the latter was to assess offlabel use. We found that the rate of prescriptions contraindicated for age increased with age (Table 1), while the frequency of off-label prescription decreased with age in other studies [4, 6]. The lower rates of drugs contraindicated for age in younger children is probably partly due to a greater reluctance on the part of physicians to go beyond contraindication for age in this group. Among 5,911 prescribers, 48.4% prescribed at least one drug contraindicated for age. This rate was highest among general practitioners (78.6%) and paediatricians (74.4%). Therapeutic classes most frequently prescribed that were contraindicated for age were topical and systemic drugs for ear, nose and throat (ENT) symptoms (24.5%), topical Eur J Clin Pharmacol (2007) 63:99–101 DOI 10.1007/s00228-006-0227-7

Corticothérapie postnatale chez le prématuré: étude des pratiques des centres français de néonatologie en 2006

BACKGROUND AND AIMnIn 1999, 80% of French neonatal centers used corticosteroids, mainly betamethasone (BMT), to prevent or treat bronchopulmonary dysplasia (BPD) [Lee SK, McMillan DD, Ohlson A, et al. Variations in practice and outcomes in the canadian NICU Network 1996-1997. Pediatrics 2000;106:1070-9]. As many data suggested a low risk-benefit ratio, an updated assessment of this use was necessary [Desnoulez L, Empana J, Anceschi M, et al. Prise en charge de limmaturité pulmonaire en néonatologie : enquête sur les pratiques européennes. Arch Pediatr 2005;12:4-9; Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (less than 96h) corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2003:CD001146; Yeh TF, Lin YJ, Lin HC, et al. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 2004;350:1304-13; Lin YJ, LKin CH, Wu JM, et al. The effects of early postnatal dexamethasone therapy on pulmonary outcome in premature infants with respiratory distress syndrome: a 2-year follow-up study. Acta Paediatr 2005;94:310-16].nnnMETHODSnQuestionnaires addressing the use of and indications for corticosteroids were sent to all French neonatal centers.nnnRESULTSnThe study was conducted over 5 months (July to November 2006). Of 202 questionnaires sent out, 186 (92%) were completed. Of these 186 centers, 147 (79%) had a standard protocol for corticosteroid use, covering systemic and inhaled steroids (76 units), only systemic steroid therapy (30 units) and only inhaled steroids (41 units). Systemic corticosteroids were used in 106 centers for hemodynamic purposes in 42 cases (40%), prevention of BPD in 1 case (1%), early treatment of BPD (day 4 to day 21) in 23 cases (22%) and late treatment of BPD (after day 21) in 74 cases (70%). Hemisuccinate hydrocortisone (HSHC) was the only corticoid used for hemodynamic failure. The steroid used for early treatment of BPD was BMT (21 out of 23). The duration of treatment was less than 4 days in 10 centers (43%). The steroid most often used for late treatment was BMT (67 out of 74). The duration of treatment was less than 4 days in 29 centers, between 4 and 8 days in 22 centers, and longer than 8 days in 26 centers. Among 117 centers administering corticosteroids by inhalation, 74% used budesonide. Use of corticosteroids was higher in teaching hospitals (86%) than in others (49%), likely due to the immaturity of the neonates hospitalized in these centers.nnnCONCLUSIONnWe showed a still frequent use of corticosteroids in preterm infants in France but only after the fourth day of life to treat BPD and not as a prevention therapy. We also found a marginal use of DXM in accordance with both short-term and long-term adverse side effects, suggesting an unbalanced risk-benefit ratio even though it has a beneficial effect on respiratory status. Our findings indicate the need for national recommendations and trials to assess oral BMT treatment in premature neonates with BPD.

De l'évaluation à la prescription des médicaments en pédiatrie

De nombreux medicaments destines aux enfants sont donnes hors amm. Cela s’explique par l’etroitesse du marche pediatrique qui n’incite pas les industriels a developper les specialites adaptees a l’enfant, par l’absence de mesure incitative pour ce developpement, par des difficultes techniques et par les contraintes d’application de la loi portant sur la protection des personnes. L’evaluation d’un medicament destine a l’enfant est pourtant indispensable en raison des particularites pharmacocinetiques et pharmacodynamiques propres a l’enfant. Le retard d’evaluation des medicaments soustrait l’enfant a certains progres therapeutiques et l’expose a un risque medicamenteux accru. La prescription en pediatrie doit obeir a un certain nombre de regles qui dependent de la situation administrative du medicament et de la prise en compte du rapport benefice-risque, surtout en prescription hors amm. Dans tous les cas, une contre-indication fondee sur un risque reel chez l’enfant ne doit pas etre outrepassee.