Center Regional Of Pharmacovigilance

Sainte-Foy-lès-Lyon, France

Center Regional Of Pharmacovigilance

Sainte-Foy-lès-Lyon, France
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Renet S.,AP HP | Chaumais M.-C.,AP HP | Chaumais M.-C.,French Institute of Health and Medical Research | Chaumais M.-C.,University Paris - Sud | And 14 more authors.
Gastroenterology | Year: 2015

Sofosbuvir and daclatasvir are direct-acting antiviral drugs used to treat chronic hepatitis C virus infection. In 2015, the Food and Drug Administration and European Medical Agency warned that bradycardia could occur when amiodarone was administered in combination with sofosbuvir, but no case reports had been published. We report extreme bradycardia within 2 hrs after intake of sofosbuvir and daclatasvir by 2 patients receiving amiodarone. The first patient had a cardiac asystole 30 min after receiving sofosbuvir and daclatasvir. Amiodarone, sofosbuvir, and daclatasvir treatment were stopped; after 10 days, the cardiac evaluation was normal and patient was discharged. The second patient was taking amiodarone and propranolol; 2 hrs after receiving sofosbuvir and daclatasvir, he had an extreme sinus node dysfunction (heart rate of 27beats/min). Amiodarone and propranolol were stopped, but the patient continued receiving sofosbuvir and daclatasvir for 3 days and sinus bradycardia was recorded each day, 2 hrs after intake of these drugs. When he stopped taking the drugs, no bradycardia was observed. Administration of sofosbuvir and daclatasvir on day 13 induced bradycardia 2 hrs after intake. However, no bradycardia occurred following a rechallenge 8 weeks after the patient stopped taking amiodarone. These observations indicate that patients treated with amiodarone should be continuously monitored within the first 48 hrs following the initiation of sofosbuvir and daclatasvir. © 2015 AGA Institute.

Fujii H.,University of Toronto | Goel A.,University of Toronto | Bernard N.,Center Regional Of Pharmacovigilance | Pistelli A.,Florence Teratogen Information Service | And 10 more authors.
Neurology | Year: 2013

Objectives: Our objectives were to 1) determine whether first-trimester use of gabapentin is associated with an increased risk for major malformations; 2) examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean birth weight and gestational age at delivery; and 3) examine rates of poor neonatal adaptation syndrome following late pregnancy exposure. Methods: The study design was prospective. Women were included who initially contacted the services between 5 and 8 weeks with a comparison group of women exposed to nonteratogens, collected in a similar manner. Results: We have data on 223 pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies. The rates of major malformations were similar in both groups (p = 0.845). There was a higher rate of preterm births (p = 0.019) and low birth weight <2,500 g (p = 0.033) in the gabapentin group. Among infants who were exposed to gabapentin up until delivery, 23 of 61 (38%) were admitted to either the neonatal intensive care unit or special care nursery for observation and/or treatment, vs 6 of 201 (2.9%) live births in the comparison group (p < 0.001). There were 2 cases of possible poor neonatal adaptation syndrome in neonates exposed to gabapentin close to delivery, compared with none in the comparison group, although it must be noted that these infants were concomitantly exposed to other psychotropic drugs. Among the women who took gabapentin, the major indications were pain (n = 90; 43%) and epilepsy (n = 71; 34%); the remainder were for other indications, mostly psychiatric. Conclusion: Our results suggest that although this sample size is not large enough to make any definitive conclusions, and there was no comparator group treated with other antiepileptic drugs, gabapentin use in pregnancy does not appear to increase the risk for major malformations. This finding and the increased risk for low birth weight and preterm birth require further investigation. © 2013 American Academy of Neurology.

Faillie J.-L.,Center Regional Of Pharmacovigilance | Faillie J.-L.,University Paul Sabatier | Petit P.,Center Regional Of Pharmacovigilance | Montastruc J.-L.,University Paul Sabatier | Hillaire-Buys D.,Center Regional Of Pharmacovigilance
Drug Safety | Year: 2013

Pioglitazone, a peroxisome proliferator-activated receptors (PPAR) agonist, has been authorized for the management of type 2 diabetes since 1999 in the US and since 2000 in Europe. Since then, the risk of bladder cancer associated with pioglitazone use has been a serious concern. Following a warning from the Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps) [the French Agency for the Safety of Health Products], use of pioglitazone was suspended in France and Germany in June 2011. Elsewhere, restrictions on prescriptions were implemented, though for both the European Medicines Agency and the US Food and Drug Administration, the risk-benefit ratio remains favourable. Since the development of pioglitazone, its risk assessment has suffered from several inaccuracies such as its alleged specificity for the male rat, untrustworthy selective agonism for PPARγ and mistaken risk evaluation in the large PROactive trial (PROspective pioglitAzone Clinical Trial In macroVascular Events), where one case with a benign tumour in the placebo group was counted as a cancer case. It took until 2011 for the epidemiological data to be sufficiently numerous and conclusive to initiate application of safety measures. Today, the increased risk of bladder cancer associated with pioglitazone seems to be real, but the absolute risk is relatively low. However, in the context of weak efficacy in an extensive population of patients exposed to pioglitazone, the risk-benefit balance is now difficult to assess, and prescription restrictions do not ensure safety. For future risk management, the authors propose several suggestions, which involve an increasing role of health authorities and academic organizations. © 2013 Springer International Publishing Switzerland.

Lillo-Le Louet A.,Center Regional Of Pharmacovigilance | Toussaint Y.,French Institute for Research in Computer Science and Automation | Villerd J.,French Institute for Research in Computer Science and Automation
Studies in Health Technology and Informatics | Year: 2010

"Pharmacovigilance is the process and science of monitoring the safety of medicines, consisting in (i) collecting and managing data on the safety of medicines (ii) looking at the data to detect 'signals' (any new or changing safety issue)" [1]. Pharmacovigilance is mainly based on spontaneous reports: when suspecting an adverse drug reaction, health care practitioners send a report to a spontaneous reporting system (SRS). This produces huge databases containing numerous reports and their manual exploration is both cost and time prohibitive. Existing techniques that automatically extract relevant signals rely on statistics or Bayesian models but do not provide information to the experts about possible biases lying in the data, nor about the specificity of a signal to a particular patient profile. Our extraction method combines numerical methods from the state of the art with a qualitative approach that helps interpretation. We build a synthetic representation of the database that is used to (i) identify unexpected patterns and biases (ii) extract potentially relevant signals w.r.t. patient profiles (iii) provide traceability facilities between extracted signals and raw data. © 2010 IMIA and SAHIA. All rights reserved.

Taugourdeau-Raymond S.,Center Regional Of Pharmacovigilance | Rouby F.,Center Regional Of Pharmacovigilance | Default A.,Center Regional Of Pharmacovigilance | Jean-Pastor M.-J.,Center Regional Of Pharmacovigilance
European Journal of Clinical Pharmacology | Year: 2012

Purpose Bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor, is widely used in association with standard chemotherapy in metastatic cancer. Well tolerated, bevacizumab is sometimes associated with serious adverse drug reactions (ADRs). The objective of this study is to describe the profile of ADRs related to bevacizumab and reported to the French Pharmacovigilance system. Method All serious cases of ADRs associated with bevacizumab recorded in the French Pharmacovigilance database up to November 31, 2010 were identified and analyzed, focusing on patient information, drug exposure, and characteristics of the ADRs. Categorical variables were compared using the chisquare test when appropriate. Results A total of 351 serious cases involving 626 ADRs were recorded in the database during the study interval. The most frequent ADRs reported involved the gastrointestinal system (21.9%). The most frequent ADRs included gastrointestinal perforation (4.8%), thromboembolic events (4.0%), pulmonary embolism (3.2%), hypertension (2.7%), gastrointestinal hemorrhage (2.7%), and cerebral hemorrhage or vascular accident (2.6%). The median duration of bevacizumab exposure was four cycles (range 1-30) when ADRs occurred. In 18 cases of death directly caused by ADRs, 50% occurred after only one cycle. In cases of disability, 40% of ADRs were neurologic: neuropathy, paralysis, and paresis. Conclusion To the best of our knowledge, this is the first analysis of bevacizumab safety profile using data collected in a national pharmacovigilance database. Our study confirms the frequency and seriousness of gastrointestinal, thromboembolic, and hemorrhage events with bevacizumab use and provides a picture of the bevacizumab safety profile in daily medical practice, despite intrinsic limitations. © Springer-Verlag 2012.

Pell G.,Service de Nephrologie transplantation Renale | Shweke N.,Service de Nephrologie transplantation Renale | Van Huyen J.-P.D.,Service dAnatomo pathologie | Tricot L.,Service de Nephrologie transplantation Renale | And 4 more authors.
American Journal of Kidney Diseases | Year: 2011

Intravenous injection of angiogenesis-inhibitor drugs is used widely to treat cancers. Associated renal complications primarily involve proteinuria and hypertension, and thrombotic microangiopathies also have been described. Intravitreal antivascular endothelial growth factor (VEGF) therapy currently is used by ophthalmologists to treat neovascularization in age-related macular degeneration. However, there is some evidence that intravitreal anti-VEGF injections may result in systemic absorption, with the potential for injury in organs that are reliant on VEGF, such as the kidney. We report the first case to our knowledge of a patient who developed an acute decrease in kidney function, nonimmune microangiopathic hemolytic anemia with schistocytes, and thrombocytopenia after 4 intravitreal injections of ranibizumab. Light microscopy of a kidney biopsy specimen showed segmental duplications of glomerular basement membranes with endothelial swelling and several recanalized arteriolar thrombi. Because of the increasing use of intravitreal anti-VEGF agents, ophthalmologists and nephrologists should be aware of the associated risk of kidney disease. Early detection is crucial so that intravitreal injections can be stopped before severe kidney disease occurs. © 2011 National Kidney Foundation, Inc.

Many observational and meta-analysis studies suggested a decreased risk of cancer in patients treated with metformin. However multiple biases have been related to these studies which are known to increase downward the effect of the drug, thus making metformin seems to be protective when in fact it may have less or no effect. Large randomized studies on diabetes treatment did not confirm any protective effect for metformin. The potential effect of sulfonylureas and glinides on cancer risk and mortality has been suggested in several observational studies mainly showing an increased risk for colorectal and pancreatic cancers. The randomized trials ADOPT and RECORD did not find such an exaggerated risk. Two meta-analysis have given divergent results with regard to cancer risk. The first one showing an increased risk for cancer in users of sulfonylureas with or without insulin compared to non users. The second metaanalysis found no risk when users of sulfonylureas without insulin were compared to others patients. A cohort study in the French National Healthcare Insurance Database between 2003 and 2010 suggested a two-fold risk of cancer in patients more exposed to sulfonylureas. It appears difficult to know whether cancer risk excess is due to sulfonylureas itself or to associated insulin treatment, or yet explained by the lower risk seen in control group treated with metformin. According to the results of observational studies, two meta-analysis found a higher risk for any cancer in insulin users. French National Healthcare Insurance Database likewise suggested a two-fold increased risk of cancer in patients highly exposed to insulin. Main criticism pointed out these studies have potential biases as insulin-treated patients have a diabetes with a longer duration and more severe comorbidities (among them cancer). The initial warning on insulin glargine appeared to be erased whereas it remains necessary to have more long term safety studies. In diabetics with high risk or antecedents for cancer, epidemiological, clinical trials and experimental data converge for first promoting combining and reinforcing therapies against insulin resistance. © 2014 - Elsevier Masson SAS.

Rouzes A.,Center Regional Of Pharmacovigilance | Jonville-Bera A.-P.,Center Regional Of Pharmacovigilance
Therapie | Year: 2014

Because of its teratogenicity, isotretinoin is contraindicated in pregnant women and also among women of childbearing age in the absence of effective contraception. The objective of this work is to summarize the results of studies assessing the effects of regulatory measures successively implemented in France since 1996 to prevent foetal exposure to isotretinoin. The five pharmacovigilance studies have shown persistence of pregnancies exposed to isotretinoin, with an estimated incidence in the latter study, between 0.32 and 0.95 per 1000 treated women of childbearing age. The strengthening of the prevention plan of pregnancies, established in France in March 2010, seems to have resulted in a decrease in the incidence of pregnancies exposed, but this trend needs to be confirmed. However, these pregnancies are almost preventable, because most of them are explained by the non-compliance with the conditions of prescribing and dispensing. Then it seems mandatory to not deliver oral isotretinoin if it is not prescribed in accordance with the prescription laid down by the authorities. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Babai S.,Center Regional Of Pharmacovigilance | Auriche P.,Afssaps | Le-Louet H.,Center Regional Of Pharmacovigilance
Therapie | Year: 2010

Background. Since donepezil and memantine are currently used for treating Alzheimer's disease, it is interesting to analyse, reassess and compare their safety profile in order to promote a better use. Methods. All spontaneous reports of suspected serious adverse drug reactions with donepezil alone and with memantine alone recorded in the French Pharmacovigilance Database during 6 years were retrospectively analysed. Results. The most frequent adverse drug reactions with donepezil alone and memantine alone were respectively: bradycardia (10% versus 7%), weakness (5% versus 6%) and convulsions (4% versus 3%). Conclusion. The most adverse drug events with donepezil and with memantine are associated with elderly people, even if they do not receive any other treatment. Donepezil and memantine have an acceptable safety profile but physicians should take special care when they prescribe any drug known to cause bradycardia or to reduce the epileptogenic threshold. © 2010 Société Française de Pharmacologie et de Thérapeutique.

Beau A.-B.,University of Monastir | Hurault-Delarue C.,University of Monastir | Vial T.,Center Regional Of Pharmacovigilance | Montastruc J.-L.,University of Monastir | And 2 more authors.
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2014

Objective To compare pregnancy outcome between women exposed and unexposed to oseltamivir during pregnancy. Design A comparative observational cohort study of women exposed to oseltamivir during pregnancy. Setting A French prescription database (EFEMERIS) that includes data for pregnant women was used. EFEMERIS records prescribed and dispensed reimbursed drugs during pregnancy and pregnancy outcomes in Haute-Garonne, South West France. Population Women who delivered from 1 July 2004 to 31 December 2010. Methods The study compared exposed and unexposed pregnant women. Two women unexposed to oseltamivir were individually matched, by maternal age, month, and year of delivery, with one women exposed to oseltamivir. Multivariable conditional logistic regression and multivariable Cox proportional hazards regression were used to evaluate associations between each outcome and exposure to oseltamivir during pregnancy. Main outcome measures Pregnancy loss for any cause, preterm delivery, low birthweight, neonatal pathology, and congenital malformation. Results A cohort of 337 (0.58% of women included in EFEMERIS) women exposed to oseltamivir were compared with 674 unexposed women. The risk for pregnancy loss (HR 1.52; 95 % CI 0.80-2.91), for preterm birth (adjusted OR 0.64; 95% CI 0.31-1.27), and for neonatal pathology (adjusted OR 0.62; 95% CI 0.23-1.54) did not differ between exposed and unexposed groups. When exposure during organogenesis was considered, one case of congenital anomaly (2.0%) among 49 exposed women and one case (1.0%) among 99 unexposed women were observed (crude OR 2.00; 95% CI 0.13-32.00). Conclusions There was no significant association between adverse pregnancy outcomes and exposure to oseltamivir during pregnancy. © 2014 Royal College of Obstetricians and Gynaecologists.

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