Sales of macrolides, lincosamides, streptogramins, and amoxicillin/clavulanate in the in- and outpatient setting in 10 European countries, 2007-2010

Monitoring the use of antibiotics is relevant due to the public health impact of microbial resistance, adverse effects, and costs. We present data on the consumption of macrolides, lincosamides, streptogramins and amoxicillin/clavulanate (AMC) between 2007 and 2010 in the in-and outpatient healthcare setting in 10 European countries provided by IMS Health. Antibiotics were classified according to the anatomical therapeutic chemical classification and consumption was expressed in defined daily doses/1000 inhabitants/day (DIDs). We analysed the number of prescriptions by diagnostic codes between 2008 and 2010, based on the International Classification of Diseases, 10th revision (ICD-10). These ICD-10 codes were grouped into four main categories: respiratory infections, genitourinary infections, other infections and other diagnoses. In 2010, the consumption of macrolides and lincosamides ranged from 0.45 DIDs (Sweden) to 5.46 DIDs (Italy),and from 0.04 DIDs (Denmark) to 1.00 DID (Germany),respectively. Streptogramins were available in France, Germany, Italy, Norway, Spain and United Kingdom with a consumption of < 0.001 DID exclusively in the hospital setting. The consumption of AMC ranged from < 0.001 DIDs (Norway) to 11.67 DIDs (Spain). During the study period, the consumption of macrolides decreased, the consumption of AMC increased in most of European countries, and lincosamides varied very slightly. Macrolides and AMC were mainly prescribed for respiratory infections in all countries but United Kingdom, where most of the prescriptions were assigned to diagnostic codes not clearly related with an infection. Lincosamides were prescribed for the respiratory infections and other infections groups. There was a wide inter-country variability in the percentage of the prescriptions assigned to each of the diagnostic categories. The inter-country differences in the consumption of these antibiotics and their prescription by diagnostic categories point to an inappropriate use of antibiotics

Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database

Gabapentin; Pregabalin; Atrial Fibrillation; ElderlyGabapentin; Pregabalin; Fibril·lació auricular; Gent granGabapentina; Pregabalina; Fibrilación atrial; AncianosINTRODUCTION: Gabapentin and pregabalin are widely prescribed to elderly people, but data on their pharmacokinetics, safety, and efficacy in this population are scarce. Neurological adverse effects are common. Atrial fibrillation (AF) associated with their use has been described in several case reports and case series, but the incidence is unknown. OBJECTIVE: The aim of this study was to assess the association between exposure to gabapentin or pregabalin and AF in the elderly. METHODS: Patients ≥ 65 years of age starting treatment with either gabapentin or pregabalin between January 1 and March 31, 2015, free of cardiovascular disease, and who did not receive the alternate study medications were studied. They were compared with patients who initiated treatment with an analgesic opiate or with alprazolam or diazepam. The two primary outcome variables were a first claim of an oral anticoagulant plus an antiarrhythmic drug (OAC + AA), or of an oral anticoagulant or an antiplatelet agent plus an antiarrhythmic drug (OAC/APA + AA), in the 3 months after treatment initiation. RESULTS: Compared with opiate analgesics, both gabapentin and pregabalin were associated with an increased risk of initiating OAC/APA + AA. The incidence was 6 of 668 (9.0 per 1000 patients) with gabapentin, versus 12 of 3889 (3.1 per 1000) with opiates, relative risk (RR) 2.91 (95% confidence interval [CI] 1.10-7.73), and for pregabalin it was 6 of 698 (8.6 per 1000) RR 2.79 (95% CI 1.05-7.40). The comparison with alprazolam/diazepam gave similar results. The risks did not vary by age, sex, or co-treatment with NSAIDs, and they increased with dose. CONCLUSION: In elderly patients free of cardiovascular disease, an association between new exposure to gabapentin or pregabalin and initiating treatment for AF was found. These results should be confirmed in other studies

Identificació de reaccions adverses greus a nous medicaments

Des dels anys seixanta, la farmacovigilància s'ha basat en la notificació de casos. Des dels vuitanta, els estudis observacionals han identificat nous efectes adversos de medicaments amb fort impacte de salut pública, i n'han quantificat el risc. Des dels 2000, els assaigs clínics i les metanàlisis també han contribuït de manera significativa al descobriment i avaluació del risc d'efectes indesitjats relativament freqüents. El Butlletí Groc s'ha fet ressò de les novetats esdevingudes durant 30 anys en l'estudi dels efectes adversos dels medicaments i el seu impacte sobre la salut pública, i pot ser un observatori del que s'ha descobert, ha preocupat i ha estat motiu de polèmiques. L'objectiu d'aquest treball és examinar l'evolució dels mètodes, els fàrmacs i les patologies de més interès en farmacovigilància a través dels articles publicats al Butlletí Groc en un període de 23 anys. Els articles publicats a Butlletí Groc entre 1988 i 2011 es van classificar en cinc categories i se'n van seleccionar els relatius a toxicitat, per analitzar els fàrmacs i els grups terapèutics implicats (segons l'ATC) i els efectes adversos (segons MedDRA). Les reaccions adverses implicades en els problemes de seguretat d'un fàrmac o grup de fàrmacs van ser classificades segons el mecanisme d'acció (A o B) i el mètode emprat per identificar-les. Dels medicaments retirats a Espanya de 1982 a 2013 per inseguretat, també es van avaluar els fàrmacs i les reaccions adverses implicades, així com el tipus de reacció, el mètode identificat i el temps de comercialització. De 244 articles publicats a Butlletí Groc en el període 1988-2011, 184 van tractar sobre inseguretat de medicaments. Dels 116 seleccionats, 132 feien referència a problemes de seguretat d'un fàrmac o grup de fàrmacs. Els principals grups de fàrmacs implicats van ser d'acció sobre el sistema nerviós, cardiovascular, AINE i altres sobre el sistema musculoesquelètic, fàrmacs actius sobre l'aparell digestiu i el metabolisme, i antiinfecciosos sistèmics. Les principals reaccions adverses van ser hepatobiliars, cardiovasculars, psiquiàtriques i neurològiques. La meitat de les reaccions adverses descrites van ser de tipus A, i l'altra meitat de tipus B, però les patologies han canviat amb el temps, de manera que ha augmentat l'interès pels efectes adversos de tipus A, a expenses dels de tipus B. Paral·lelament, han canviat els mètodes d'identificació i avaluació de la relació causal de la reacció adversa amb l'exposició al medicament, de manera que els estudis observacionals, assaigs clínics i metanàlisis han substituït en part les notificacions i les sèries de casos. La proporció de fàrmacs amb valor intrínsec nul o inacceptable s'ha reduït a partir dels anys noranta. L'anàlisi dels fàrmacs retirats a Espanya entre 1982 i 2013 revela que els principals grups terapèutics implicats van ser els actius sobre el sistema locomotor, nerviós, cardiovascular i digestiu. Els principals subgrups van ser AINE, fàrmacs per a l'obesitat, antidepressius i vasodilatadors. Durant els 30 anys d'observació, el temps transcorregut entre la comercialització i la retirada d'un fàrmac per motius d'inseguretat s'ha allargat, d'uns 8 anys entre 1982-99 al doble entre 2000-03. Les reaccions adverses més freqüents han estat hepàtiques, cardiovasculars i neuropsiquiàtriques. L'hepatotoxicitat ha estat la principal causa de retirades de medicaments durant tot el període d'estudi, però a partir del 2000 les reaccions cardiovasculars són les causes més freqüents. Els motius principals de preocupació han evolucionat des de les reaccions adverses rares i més greus de tipus B, a les de tipus A, de més incidència sobre la salut pública. Els mètodes emprats per decidir retirar un medicament també han evolucionat des de les sèries de casos els primer anys fins als estudis observacionals i les metanàlisis d'assaigs clínics, com a principals generadors de senyals i de quantificació de riscos.In the 1960's, pharmacovigilance was mainly based on case reports. Since the 1980's, observational studies helped to identify new adverse drug reactions which have a big impact on public health, and they have also quantified their risk. Since 2000, clinical trials and meta-analysis have also contributed significantly to the discovery and evaluation of the risk of relatively frequent adverse effects. In the last 30 years, Butlletí Groc has reported on all the news regarding s adverse drug effects and their impact on public health, and through this magazine we can learn about the discoveries, concerns and controversies. The aim of this study is to examine the evolution of methods, drugs and diseases of interest in pharmacovigilance looking at articles published in Butlletí Groc over a period of 23 years. The articles published in Butlletí Groc from 1988 to 2011 were classified into five categories. Those related to toxicity were selected to analyze drugs and therapeutic groups involved (according to ATC) and adverse effects (according to MedDRA). Adverse reactions related to safety problems of a drug or group of drugs were classified according to the mechanism of action (type-A or type-B) and the method used to identify them. Of the drugs withdrawn from the market in Spain from 1982 to 2013 due to safety reasons, drugs and adverse reactions involved were also evaluated, as well as the type of reaction, the method identified, and time to market. Among 244 articles published in Butlletí Groc between 1988 and 2011, 184 dealt with drug toxicity. Of the 116 selected, 132 were concerned with safety problems of a drug or group of drugs. The main groups of drugs involved were those active on the nervous system, cardiovascular, NSAIDs and others active on the musculoskeletal system, active drugs on the digestive system and metabolism, and systemic anti-infectives. The main adverse reactions led to hepatobiliary, cardiovascular, psychiatric and neurological diseases. Half of the adverse reactions were described as type-A, and half type-B, but the diseases have changed over time, so there has been increasing interest in the effects of type-A, at the expense of type-B. Meanwhile, the methods of identification and assessment of adverse reaction causal relationship with exposure to the drug have changed, so that observational studies, clinical trials and meta-analysis have partly replaced reporting and case series. The proportion of drugs with no intrinsic value or described as unacceptable has fallen since the 1990's. The analysis of the drugs withdrawn in Spain from 1982 to 2013 reveals that the main therapeutic groups involved were those active on the musculoskeletal, nervous, cardiovascular, and digestive systems. The main subgroups were NSAIDs, drugs for obesity, anti-depressants, and vasodilators. During 30 years of observation, the time between the marketing and the withdrawal of a drug for safety reasons has lengthened rising, from 8 years between 1982 and 99 to double the length of time between 2000 and 2003. The most frequent adverse reactions were hepatic, cardiovascular, and neuropsychiatric. Hepatotoxicity has been the main cause of drug withdrawals during the whole study period, but since 2000 cardiovascular reactions are the most common causes. The main reasons for concern have evolved from being worried about rare and severe adverse reactions type-B to worries in type-A, which are more frequent and have more impact on public health. The methods used in deciding to withdraw a drug have also evolved since the case series in the early years to using observational studies and meta-analysis of clinical trials, which are mainly used to detect problems and quantify risks

La consulta terapèutica : una eina complementària d'informació per a la individualització de la terapèutica

En aquest article es presenten els resultats d'un treball de recerca que analitza les característiques de la demanda d'informació sobre terapéutica atesa durant els darrers quinze anys a la Fundació Institut Catalá de Farmacologia. En una época en qué, per una banda, el volum creixent de nova informació médica disponible fa que al metge sovint sigui difícil mantenir-se al dia i, per una altra banda, davant la progressiva acceptació de la medicina basada en proves, la prestació d'un servei de consulta terapéutica representa una activitat complementária d'informació en la qual s'utilitzen les millors evidencies disponibles per a la individualització de la terapéutica