Publications by authors named "Haleh Bagheri"

123 Publications

Lacosamide-induced personality changes: An unexpected adverse effect.

Fundam Clin Pharmacol 2021 May 7. Epub 2021 May 7.

Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, CHU de Toulouse, Université de Toulouse, INSERM U1027, Faculté de Médecine - Toulouse.

Objectives: To describe an "unexpected" case of abrupt personality following the introduction of lacosamide.

Methods: A description of an 82-year-old male receiving neurological follow-up since 2010 due to epilepsy secondary to haemorrhagic stroke. We report a case of abrupt personality change in an 82-year-old male following the introduction of lacosamide with a return to the previous state after its discontinuation. We explored possible mechanisms and pharmacokinetic concerns explaining this personality change.

Results: In fact, a few days after introducing lacosamide, the patient was described as "gentle", "calm" and apologetic for his past aggressions against his family and caregivers which was in complete contrast to his usual personality. There was also marked insistence and the use of sexualised language towards women in his close circle, especially his home nurses. In view of his insistent behaviour towards his nurses and unusual sexualised language, lacosamide was withdrawn. A few days later, the patient displayed his usual, vindictive, aggressive and forceful character. He no longer made any sexualised remarks to his home nurses.

Conclusion: To our knowledge, this is the first case of a sudden behavioural and personality change reported by family, friends and carers following the introduction of lacosamide.
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http://dx.doi.org/10.1111/fcp.12692DOI Listing
May 2021

Fatal adverse drug reactions: A worldwide perspective in the World Health Organization pharmacovigilance database.

Br J Clin Pharmacol 2021 Apr 10. Epub 2021 Apr 10.

Service de Pharmacologie Médicale et Clinique, Centre de PharmacoVigilance de Pharmacoépidémiologie et d'Informations sur le Médicament, CIC INSERM, Centre Hospitalier Universitaire-Faculté de Médecine de Toulouse, 1436, France.

Aims: Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death-related drugs recorded in a large pharmacovigilance database during the last 10 years.

Methods: A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval.

Results: Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years.

Conclusion: Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries.
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http://dx.doi.org/10.1111/bcp.14851DOI Listing
April 2021

[Amiodarone or COVID induced-pneumopathy: One train can hide another one!]

Therapie 2021 Mar 6. Epub 2021 Mar 6.

Service de pharmacologie médicale et clinique, centre de pharmacovigilance, de pharmacoépidémiologie et d'informations sur le médicament, faculté de médecine, centre hospitalier universitaire, UA 1320, 7, allées Jules-Guesde, 31000 Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/j.therap.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936754PMC
March 2021

Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns.

Clin Microbiol Infect 2021 Feb 27. Epub 2021 Feb 27.

Department of Cardiology, Toulouse University Hospital (CHU), Faculty of Medicine, Toulouse, France. Electronic address:

Objectives: In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is associated with an increased risk of bradycardia.

Methods: Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23 September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CI.

Results: We found 302 cardiac effects including 94 bradycardia (31%) among the 2603 reports with remdesivir prescribed in COVID-19 patients. Most of the 94 reports were serious (75, 80%), and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23-2.22). Consistent results were observed in other sensitivity analyses.

Discussion: This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with the pharmacodynamic properties of remdesivir.
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http://dx.doi.org/10.1016/j.cmi.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910147PMC
February 2021

Risk comparison of beta-lactam-induced anaphylaxis: Therapeutic stratification analysis in a Vietnamese pharmacovigilance database.

J Clin Pharm Ther 2021 Feb 10. Epub 2021 Feb 10.

Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine de l'Université Paul-Sabatier (Medical and Clinical Pharmacology Laboratory, Faculty of Medicine Paul-Sabatier University) and Centre de PharmacoVigilance, de Pharmacoépidémiologie et d'Information sur le Médicament de Toulouse (Centre for Pharmacovigilance, Pharmacoepidemiology and Drug Information), UMR INSERM 1027, Centre Hospitalier Universitaire de Toulouse (Toulouse University Hospital Centre), Toulouse, France.

What Is Known And Objective: There is limited data on the specific risks of anaphylaxis induced by beta-lactam drugs. The aim of this study was to compare the risks of reporting beta-lactam-induced anaphylaxis using the national pharmacovigilance database of Vietnam (NPDV).

Methods: The multivariate generalised linear regression model was applied for signal generation and comparison of beta-lactams.

Results: Between 2010 and 2016, there were 2,921 reports of anaphylaxis (19.93%) from 14,655 spontaneous reports of beta-lactam use in the NDPV. Anaphylaxis signal generation was also found for the subgroup J01D (cephalosporins and carbapenems) (ROR = 1.27 [1.16-1.39]) and beta-lactamase-sensitive penicillins (ROR = 1.74 [1.27-2.35]). In the third generation cephalosporin subgroup, different risks were identified for the following combinations of beta-lactams: 1) cefotaxime with cefoperazone+sulbactam; 2) cefixime/cefpodoxime/cefdinir with cefoperazone+sulbactam or ceftizoxime/cefoperazone/ceftazidime/ceftriaxone/cefotaxime. For the second generation cephalosporin subgroup, different risks were found for cefotiam compared to cefmetazole, cefaclor, cefamandole and cefuroxime.

What Is New And Conclusion: These findings identified and highlighted the different anaphylactic risks caused by various beta-lactams in the main subgroups.
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http://dx.doi.org/10.1111/jcpt.13376DOI Listing
February 2021

Severe hypertensive flare-up after intravitreal injection of ranibizumab for retinal venous branch occlusion.

Fundam Clin Pharmacol 2020 Nov 23. Epub 2020 Nov 23.

Service d'Hypertension Artérielle et Thérapeutique, Pôle Cardiovasculaire et Métabolique, Centre Hospitalier Universitaire Rangueil, Toulouse, 31059, France.

Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of angiogenesis. Systemic adverse effects of some anti-VEGF include hypertension, proteinuria and cardiovascular complications which could involve lower systemic VEGF levels. However, the question regarding intravitreal administration of anti-VEGF remains controversial given that the patients receiving these drugs are often elderly and present cardiac risk factors such as arterial hypertension or atrial fibrillation. We report a case of hypertensive flare-up following intravitreal injection of ranibizumab for retinal vein occlusion. The outcome was favourable after adapted antihypertensive treatment. This case report adds to the growing body of evidence suggesting that intravitreal administration of anti-VEGF, regardless of agents, may result in hypertensive episodes in some predisposed patients. Listing this adverse effect should help to minimize risks by heightening clinician and patient awareness and to improve blood pressure monitoring following the intravitreal administration of anti-VEGF agents.
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http://dx.doi.org/10.1111/fcp.12632DOI Listing
November 2020

Characteristics of self-medication in French students.

Authors:
Haleh Bagheri

Therapie 2020 Sep - Oct;75(5):417-418. Epub 2020 Sep 28.

Service de pharmacologie médicale et clinique, centre Midi-Pyrénées de pharmacovigilance, de pharmacoépidémiologie et d'informations sur le médicament, CHU de Toulouse, université de Toulouse, Inserm U1027, 31000 Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/j.therap.2020.09.006DOI Listing
September 2020

[Analysis of regulatory status changes of drugs in France: 2010-2019].

Therapie 2021 Jan-Feb;76(1):37-47. Epub 2020 Jul 9.

INSERM U1027, service de pharmacologie clinique et médicale, centre de pharmacovigilance et de pharmacoépidémiologie, faculté de médecine, centre hospitalo-universitaire de Toulouse, allées Jules-Guesde, 31000 Toulouse, France. Electronic address:

Objectives: The existence of borderline products between the status of a medicinal product and other less regulated products allows some products to have different statuses or even to change from one status to another. In order to quantify these changes, a review of medicines that have changed from drug status to other statuses (medical device, cosmetic product or food supplement) in France between 2010 and 2019 was performed.

Method: The lists of medicinal products with archived or revoked marketing authorization (MA) from the French National Authority's Register of Medicinal Products were analyzed in order to identify the medicinal products withdrawn from the market between January 1, 2010 and September 30, 2019 that could be considered as products with a "potential for status change". Then, we searched on the official websites of the MA holders and other firms, for a possible return to the market with a different status, marketed by the same firm (self-change of status) or a different firm (hetero-change of status).

Results: Out of a list of 206 drugs identified as "with potential for status change", we detected a total of 101 status changes, including 36 auto-changes and 65 hetero-changes. These changes mainly concern vitamin or herbal drugs later marketed as food supplements (30 cases of auto-changes and 60 cases of hetero-changes). There are also 6 cases of switching to cosmetic product and 5 cases of switching to medical device.

Conclusion: The existence of no clear distinction between the different statuses of health products facilitates their status changes. The increasing shift from "medicines" to less regulated products, the trivialization of their use by the public and their increasing consumption make them a fundamental issue of social pharmacology, requiring to raise the awareness of consumers and health professionals.
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http://dx.doi.org/10.1016/j.therap.2020.06.016DOI Listing
July 2020

[Potentially inappropriate medication: Adaptation of EU(7)PIM criteria to the French medical practice].

Therapie 2020 Nov - Dec;75(6):663-673. Epub 2020 Jun 6.

Service de pharmacologie médicale et clinique, centre de pharmacovigilance, de pharmacoépidémiologie et d'informations sur le médicament, faculté de médecine, centre hospitalier universitaire, 31000 Toulouse, France.

Objective: Improving the quality of prescribing in the elderly remains a permanent concern and a major opportunity to improve patient care. The objective of this article is to propose, from updated existing lists of potentially inappropriate medication (PIM), a list of PIM adapted to the French medical practice.

Method: Combination of an explicit tool: the updated EU (7) PIM list published in 2015, adapted to the French medical practice (availability of drugs and validated indications), and an implicit tool: the recommendations of French National Health Authority (HAS) and more specifically the "alerte et maîtrise de la iatrogénie" (AMI) tools.

Results: From 289 PIM identified in the EU(7) PIM list, 183 drugs were included in our list according to our method. Three PIM were added to the list of "questionable" PIMs in accordance with the new French recommendations. A total of 90 PIMs were removed because of their indications or their non-commercialization in France.

Conclusion: This work provides an adaptation of the EU(7)PIM to the French medical practice with the guidance of the HAS recommendations. This list is intended to be easy to use for the identification of PIMs by French physicians.
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http://dx.doi.org/10.1016/j.therap.2020.06.001DOI Listing
June 2020

Serious adverse drug reactions with hydroxychloroquine: a pharmacovigilance study in Vigibase®.

Eur J Clin Pharmacol 2020 Oct 6;76(10):1479-1480. Epub 2020 Jun 6.

Service de Pharmacologie Médicale et Clinique, Centre de PharmacoVigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Faculté de Médecine, Centre Hospitalier Universitaire, 37 allées Jules-Guesde, 31000, Toulouse, France.

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http://dx.doi.org/10.1007/s00228-020-02920-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275655PMC
October 2020

Paradoxical adverse drug reactions: descriptive analysis of French reports.

Eur J Clin Pharmacol 2020 Aug 16;76(8):1169-1174. Epub 2020 May 16.

Centre De Pharmacovigilance, De Pharmacoépidémiologie Et D'informations Sur Le Médicament, Inserm UMR 1027, Faculté De Médecine, Centre Hospitalier Universitaire, Toulouse, France.

Introduction: Paradoxical adverse drug reactions (ADRs) are defined as being opposing reactions to the pharmacological effect of drugs in relation to its pharmacodynamic properties. Their diagnosis is difficult as they are relatively rare with atypical clinical presentation (with the possibility of being confused with drug ineffectiveness or the worsening of the underlying disease). This kind of ADR may be particularly subject to under-notification. The aim of the present study is to describe paradoxical ADRs using the French PharmacoVigilance DataBase (FPVDB).

Method: We analysed all reports recorded in the FPVDB with drugs defined as "suspect" and which included the term "paradoxical reaction" (PR) (according to MedDRA classification) from 01/01/1984 to 12/31/2018. The drugs were classified according to the Chemical Therapeutic Anatomical Classification (ATC).

Results: We found 57 reports of PR, with half of them recorded between 2015 and 2018. The median age of patients was 46 years, mainly male (54%). The most frequently involved drugs were immunomodulating agents (n = 28, 49%) and psychotropics (n = 28, 49%). The leading paradoxical ADRs were psychiatric (anxiety, sleep and behavioural disorders) and skin-related. In 19 cases (33%), PR was related to benzodiazepines mainly occurring in patients in extreme ages (five cases in children and patients > 70, respectively, 53%). For psychotropic-induced PR (n = 28), known contributory factors (alcohol consumption, underlying psychiatric diseases) were found in 18 cases (64%). Paradoxical reactions with immunomodulating agents were mainly related to skin ADRs (n = 25). For psychotropics, paradoxical ADRs occurred rapidly after a mean delay of 1 day, predominantly following high doses. We also identified several "unexpected" paradoxical reactions, such as cognitive degradation with donepezil, or a return to impulsive smoking addiction with varenicline.

Conclusion: This study highlights that pharmacovigilance databases like the French database make it possible to investigate the main characteristics of paradoxical reactions to drugs. This ADR was mainly found in the FPVDB with psychotropic drugs and immunomodulating agents. Moreover, pharmacovigilance databases enable the identification of some signs of "unexpected paradoxical reactions". In order to identify this type of ADR more effectively, work on awareness and harmonization is required to register these reports. The addition of the term "paradoxical reaction to the drug" to the list of other symptoms would facilitate their identification and analysis.
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http://dx.doi.org/10.1007/s00228-020-02892-2DOI Listing
August 2020

Are potentially inappropriate and anticholinergic medications being prescribed for institutionalized elderly subjects?

Fundam Clin Pharmacol 2020 Dec 17;34(6):743-748. Epub 2020 May 17.

Department of Medical and Clinical Pharmacology, Centre for Pharmacovigilance, PharmacoEpidemiology and Information on Medications, Faculty of Medicine, INSERM UMR 1027, University Hospital and Faculty of Medicine, Toulouse, France.

The PAAPI project (Optimising Inappropriate Prescriptions in the Elderly) is a multi-disciplinary approach put in place by the Toulouse Pharmacovigilance Centre (CRPV) in order to improve drug prescribing practice in nursing homes. The aim of this study was to analyse the association between polypharmacy, frequency of prescriptions for potentially inappropriate medications (PIMs) and the anticholinergic burden of prescriptions in elderly patients from the PAAPI cohort. We carried out a retrospective study on residents of 24 nursing homes (EHPAD) participating in the PAAPI programme between 1er January 2017 and 31 December. Resident's Data were collected in a single review in a random day. Drug prescriptions were analysed quantitatively and qualitatively. PIMs and anticholinergic drugs were identified by the list EU(7)PIM and the Duran scale, respectively. The total anticholinergic burden was calculated by adding the anticholinergic scores of each drug. We classified the drugs into three categories: no anticholinergic burden (burden = 0), low anticholinergic burden (≥1 ≤ 3) or high anticholinergic burden (burden > 3). A total of 1191 residents living were included, and we analysed 8869 drug prescription lines. The average age of the residents was 87.0 ± 8.3 years, and the majority (71.5%) were female. Nearly half of the residents (49.6%, n = 67) having a prescription with a high anticholinergic burden were taking more than 9 drugs (Fisher exact test P < 0.05). All the prescriptions with more than 5 PIMs (n = 23) had an anticholinergic burden > 0, with the majority (65.2%, n = 15) having a high anticholinergic burden (Kruskal-Wallis test, P < 0.0001). In this cohort, 88% (n = 539) of prescriptions with a low anticholinergic burden and 100% (n = 135) of prescriptions with a high anticholinergic burden included at least one PIM. According to our study, the anticholinergic burden of prescriptions given to residents in the PAAPI cohort is associated with the prescription of PIMs and with polypharmacy. Optimizing the use of medicines remains essential in this population, given the harmful properties of these drugs. It would also be useful for the list of anticholinergic drugs to be updated as new medicines come onto the market.
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http://dx.doi.org/10.1111/fcp.12560DOI Listing
December 2020

The Cost of Potentially Inappropriate Medications in Nursing Homes in West Occitanie.

Pharmacy (Basel) 2020 Mar 11;8(1). Epub 2020 Mar 11.

Department of Medical and Clinical Pharmacology, Centre for PharmacoVigilance, PharmacoEpidemiology and Information on Medications, Faculty of Medicine, INSERM UMR 1027, University Hospital and Faculty of Medicine, Toulouse, France.

Introduction: As of 2019, people older than 65 years represent 20% of the French population. Despite several guidelines suggesting to avoid potentially inappropriate medication (PIM) use in elderly, the prevalence of their prescription remains high (25%). Furthermore, PIM could lead to preventable adverse drug reactions (ADRs). The main objective of this study was to determine the direct cost of PIM in older persons living in residential care homes for the elderly (nursing homes). A secondary objective was to assess the potential impact of PIM deprescribing on drug-related health care costs. : We undertook a multicenter, retrospective study in 19 care homes for the elderly including 1240 residents. The analysis of prescriptions was carried out according to the European EU(7) PIM list. The cost of each drug was estimated according to the French Medication Insurance database. Furthermore, patient's comorbidities were studied using Charlson's comorbidity index. In order to estimate the economic impact of PIM, we used the list of alternative appropriate drugs suggested by EU(7) PIM list and French National Health Authority. An incremental cost per patient was calculated by the difference in costs between PIMs and alternative drugs. : A total of 7768 lines of drug prescriptions were analyzed. The mean age was 87.6 ± 7.6 years. About 70% (n = 872) of residents received more than five drugs. We identified 959 residents (77.3%) with at least one PIM. The mean cost of PIM was 0.58 euros versus 0.48 euros for alternatives. PIM substitution by alternatives led to save 12 centimes/resident/day. The mean cost of prescription with PIM was 2.8 euros per resident per day (28% of the overall cost of prescription). According to these results, more than 25 million euros can be overall saved for aged persons living in nursing homes for the older people in France per year. : The prevalence of PIMs among the elderly in nursing homes is high and leads to a significant cost. Deprescribing of these medications could decrease both drug misuse and cost of drug prescription. Further research is needed to estimate the overall cost of PIM exposure outcomes, taking into account the ADRs leading to hospitalization.
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http://dx.doi.org/10.3390/pharmacy8010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151696PMC
March 2020

Fluoroquinolone-Induced Photosensitivity: A Chemical Fragment-Based Approach by a Case/Non-case Study in VigiBase.

Drug Saf 2020 06;43(6):561-566

Service de Pharmacologie Médicale et Clinique, Centre Régional de Pharmacovigilance, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Introduction: Fluoroquinolones are widely used to treat bacterial infections. Many in vitro and in vivo studies have established a chemical relationship between fluoroquinolones' particular chemical structure and photosensitivity. The aim of this study was to establish a relationship between the chemical structure of fluoroquinolones and the risk of photosensitivity adverse effects from real-world data.

Methods: All the Individual Case Safety Reports (ICSRs) related to fluoroquinolones and registered in the World Health Organization global database (VigiBase) up to December 31, 2017 were collected. A disproportionality analysis was performed in order to quantify the photosensitivity risk for each fluoroquinolone by calculating their reporting odds ratio (ROR).

Results: Up to December 31, 2017, 282,805 ICSRs related to fluoroquinolones were selected, of which 1647 were photosensitivity adverse event cases. Sparfloxacin had the highest adjusted ROR of 161.10 (95% confidence interval [CI] 133.66-194.02) followed by grepafloxacin (40.30 [26.30-59.60]) closely followed by lomefloxacin (32.61 [28.61-37.07]), then enoxacin (11.04 [8.33-14.32]) and fleroxacin (8.22 [5.06-12.56]).

Conclusion: This study confirms the high reporting rate of photosensitivity adverse effects for sparfloxacin from real-world data. Moreover, our data suggest more photosensitivity adverse effects reporting for fluoroquinolones with a halogen at their 8th position.
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http://dx.doi.org/10.1007/s40264-020-00917-4DOI Listing
June 2020

Platelet function defects and sertraline-induced bleeding: a case report.

Fundam Clin Pharmacol 2020 Oct 18;34(5):632-636. Epub 2020 Mar 18.

Universite Toulouse III Paul Sabatier Faculte de Medecine Purpan - Epidémiologie et Analyses en Santé Publique, Toulouse, 31000, France.

A 71-year-old man is admitted for nose bleeds recurring for several days. His medical background shows in particular major depression for which he has been receiving sertraline for several years. The workup shows anemia, and no anomalies on head and neck CT angiography. However, further explorations suggest an acquired thrombopathy that could have contributed to the bleeding. During sertraline exposure, platelet functional exploration and platelet secretion were abnormal. Sertraline is often used as first-line treatment of depression. Pharmacological data and spontaneous notifications suggest increased potential risk with sertraline. It appears necessary to pay attention to bleeding with sertraline use.
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http://dx.doi.org/10.1111/fcp.12552DOI Listing
October 2020

Drug interactions related to self-medication: a French pharmacovigilance database study.

Fundam Clin Pharmacol 2020 Oct 13;34(5):623-631. Epub 2020 Mar 13.

Service de Pharmacologie-Toxicologie et Pharmacovigilance, Centre Hospitalo-Universitaire d'Angers, 4 rue Larrey, F-49100, Angers, France.

Self-medication (SM) is a common practice perceived by patients as harmless which can, however, entail health risks. The aim of the study was to identify drug-drug interactions (DDIs) involving SM drugs leading to adverse drug reactions (ADRs) in the National French Pharmacovigilance Database. All ADR reports from 1 January 1985 to 31 July 312018, coded as 'interaction' and 'self-medication', were selected and studied. Patient characteristics, the level and type of interaction, and the therapeutic classes of the drugs were examined. Adverse drug reactions were analysed and classified according to the system organ classes of the Medical Dictionary for Regulatory Activities. One hundred and three reports totalling 158 ADRs (71% severe cases) were included; 153 DDIs (59.5% pharmacodynamic) involving 234 drugs were identified. The latter included 119 SM drugs (51% available on prescription), mainly analgaesics, anti-inflammatory drugs, dietary supplements and antibiotics. Haemostasis disorders and renal failure were the most frequently reported ADRs. The analysis of reference documents raised concerns on the lack of information provided by package leaflets. In conclusion, the present study highlights the risks of medically unapproved re-use of prescription drugs or the consumption of dietary supplements without monitoring possible interactions and ADRs. Patient awareness could be improved by more regular updates of medication package inserts.
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http://dx.doi.org/10.1111/fcp.12546DOI Listing
October 2020

Abatacept in rheumatoid arthritis and the risk of cancer: a world observational post-marketing study.

Rheumatology (Oxford) 2020 09;59(9):2360-2367

Department of Medical and Clinical Pharmacology, Centre of Pharmacovigilance and Pharmacoepidemiology, Toulouse University Hospital, Faculty of Medicine, Toulouse, France.

Objectives: We aimed to investigate whether abatacept used in patients for RA was associated with an increased risk of reporting overall cancer and specific cancers, including breast, lung, lymphoma, melanoma and non-melanoma skin cancer when compared with other biologic DMARDs (bDMARDs).

Methods: We performed an observational study within VigiBase, the World Health Organization's global database of individual case safety reports, from 2007 to 2017 to compare the cases of cancer reported in RA patients exposed to abatacept with those reported in RA patients exposed to other bDMARDs. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CIs of the exposure odds among spontaneous reporting of cancers to the exposure odds among other reported adverse effects.

Results: We identified 15 846 adverse effects reported in RA patients who received abatacept and 290 568 adverse effects reported in RA patients treated with other bDMARDs. Compared with other bDMARDs, the use of abatacept was not associated with an increased risk of reporting cancer overall [ROR 0.98 (95% CI 0.91, 1.05)]. Analyses by specific cancer sites showed a significantly increased ROR for melanoma [1.58 (95% CI 1.17, 2.08)], but not for other specific cancer sites.

Conclusion: Compared with other bDMARDs, exposure to abatacept in RA patients was only significantly associated with an increased risk of reporting melanoma. This increased risk is consistent with the properties of abatacept (CTLA-4 agonist) since it has an opposite action than ipilimumab, an antibody that blocks CTLA-4 and is approved for the treatment of malignant melanoma.

Trial Registration: ClinicalTrials.gov (http://clinicaltrials.gov), NCT03980639.
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http://dx.doi.org/10.1093/rheumatology/kez604DOI Listing
September 2020

Drug-induced osteoporosis/osteomalacia: analysis in the French and Spanish pharmacovigilance databases.

Eur J Clin Pharmacol 2019 Dec 29;75(12):1705-1711. Epub 2019 Aug 29.

Service de Pharmacologie Médicale et Clinique, Centre de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, INSERM U1027, Faculté de Médecine, Centre Hospitalier Universitaire, Toulouse, France.

Introduction: Osteomalacia and osteoporosis are two metabolic bone disorders that increase the risk of fracture due to several causes. In terms of drugs, apart from corticosteroids, which are known to induce bone disorders, several other drugs used in chronic disease management have also been linked with an increased risk of osteoporosis and osteomalacia.

Purpose: The aim of this study was to describe spontaneous reports of drug-induced osteoporosis and osteomalacia in the French (FPVDB) and Spanish (SPVDB) pharmacovigilance databases.

Methods: Data were provided by the FPVDB and SPVDB. All reports of osteoporosis and osteomalacia recorded from 1985 up to 31 December 2015 inclusive were selected. Taking the time to onset of bone loss into account, all cases occurring in less than 1 month were excluded.

Results: A total of 369 reports (44 cases of osteomalacia, 325 cases of osteoporosis) were registered in the FPVDB and 64 (22 cases of osteomalacia, 42 cases of osteoporosis) in the SPVDB. In France, the top 5 drugs involved in the onset of osteoporosis were corticosteroids accounting for approximately half of the reports (n = 170) followed by systemic antiviral (n = 87), antacid (n = 29), antiepileptic (n = 27) and antithrombotic (n = 24) drugs. The 2 main classes of drugs implicated in osteomalacia were systemic antiretroviral drugs for half of the reports (n = 21) and antiepileptic drugs (n = 15). In Spain, corticosteroids were involved in 35.7% of reported cases of osteoporosis (n = 15) followed by systemic antiviral drugs (n = 12). There was no spontaneous report for antacid drugs. For osteomalacia, the 2 main drug classes were systemic antiretroviral drugs (n = 18, 81.8%) followed by antiepileptics (n = 2, 9.0%). In both countries, concomitant administration of systemic corticosteroids with other suspected drugs did not significantly modify the time to onset of drug-induced osteoporosis.

Conclusion: Despite some differences between the French and Spanish PVDBs, our data consistently show that bone loss is not only restricted to glucocorticoids but also involves antivirals, antiepileptic drugs, antacid drugs or antidepressants. Further analysis might prove useful in exploring the characteristics of drug-induced bone loss on a larger scale.
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http://dx.doi.org/10.1007/s00228-019-02743-9DOI Listing
December 2019

[Evolution of drug prescription pattern in elderly: Retrolective study in a general hospital center in France].

Therapie 2020 May - Jun;75(3):271-279. Epub 2019 Jul 9.

Inserm UMR 1027, service de pharmacologie médicale et clinique, centre de pharmacovigilance, de pharmacoepidémiologie et d'informations sur le médicament Occitanie Ouest, faculté de médecine, centre hospitalier universitaire et faculté de médecine de l'université de Toulouse, 31000 Toulouse, France.

Background: Collaboration between general practitioners and hospital clinicians remains a major challenge for the healthcare system.

Objective: The aim of this study was to evaluate the pattern of drug prescription after an hospital stay in geriatric rehabilitation department of Bagnères-de-Bigorre hospital center, over a one year period.

Method: Quantitative and qualitative analysis of drug prescriptions for patients during their hospital admission and followed up at 6 and 12 months after their discharge.

Results: A total of 50 patients were included with a mean age of 88.9 (±7.5). The average number of drug per patient decreased from (8.5±3) at hospital admission to 6.7 (±2.8) after discharge and maintained during 6 months (6.8±2.7) and 12 months (6.9±2.9). The number of patients taking more than 10 drugs decreased by 15% (n=16 [33%] at hospital admission and n=9 [18%] at hospital discharge), re-increased during the follow-up period (n=10; [21%] and n=13 [27%] respectively 6 and 12 months after discharge) but did not reach the baseline ratio. The qualitative analysis also shows an improvement of the prescription of potentially inappropriate medications (PIM) [-3%] concerning mainly drugs with high atropinic burden (-20% at hospital discharge, -12% at 6 months and -18% at 12 months).

Conclusion: According to the indicators of our study, general practitioners followed, both quantitatively and qualitatively, modifications of drug prescriptions performed during hospitalization in patients over 65, in a short (6 months) and medium delay (12 months).
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http://dx.doi.org/10.1016/j.therap.2019.05.005DOI Listing
March 2021

Are lipid-lowering drugs associated with a risk of cataract? A pharmacovigilance study.

Fundam Clin Pharmacol 2019 Dec 17;33(6):695-702. Epub 2019 Jul 17.

Faculty of Medicine, Department of Medical and Clinical Pharmacology, Centre of PharmacoVigilance, Pharmacoepidemiology and Drug Information, INSERM UMR 1027 Pharmacoepidemiology, Assessment of Drug Utilization and Drug Safety, CIC 1426, CHU Toulouse University Hospital, Toulouse, France.

Some reports have raised concerns regarding a potential risk of cataracts associated with statins. However, clinical and observational studies evaluating the risk led to conflicting results. We assessed whether lipid-lowering drugs (LLD) use is associated with an increased risk of cataract using the WHO's Individual Case Safety Reports database, VigiBase . We performed a disproportionality analysis with all reports between 1/1/1988 and 12/31/2018 to measure the reporting risk of 'cataract' in patients ≥45 years. Primary analysis compared LLD users to non-users. To mitigate some potential confounding bias, we performed several sensitivity analyses excluding reports (i) with an association of at least two LLD, (ii) with antidiabetic and glucocorticoids and (iii) with lovastatin. We also analyzed the data according to the different classes of age limiting the period of study to years 2002-2012. We identified 14 664 reports of cataract (3 049 in LLD users, 66% women, 66 ± 20 years). Statins (84%, atorvastatin, simvastatin, rosuvastatin and lovastatin) were mostly reported, followed by fibrates (5.7%), nicotinic acid (3%), bile acid sequestrants (2%), herbal cholesterol and triglyceride reducers (2%) and others (ezetimibe, PCSK9 inhibitors, 15%). LLD users were associated with a greater risk of reports than non-users (ROR 2.47, 95% CI 2.37-2.57). This association was also found for statins in general, fibrates, bile sequestrants, nicotinic acid, herbal drugs and others. Similar trends were observed in sensitivity analyses (except for fibrates and nicotinic acid after exclusion of reports with at least two LLD or in older patients ≥75 years). Using a large real-life database (>18.5 million reports), we found a signal of cataract for LLD as a whole and statins, bile sequestrants and herbal drugs in particular. The signal disappeared for fibrates and nicotinic acid in older patients. No definite conclusions can be made for ezetimibe or PCSK9 inhibitors (evolocumab and alirocumab). This suggests that a decrease in cholesterol could be important in the pathophysiology of cataract in patients exposed to the main LLD.
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http://dx.doi.org/10.1111/fcp.12496DOI Listing
December 2019

Is TNF inhibitor exposure a risk factor for amyotrophic lateral sclerosis?

Fundam Clin Pharmacol 2019 Dec 29;33(6):689-694. Epub 2019 May 29.

Regional Pharmacovigilance Centre of Caen, University Hospital Centre of Caen, UMR, UMR University of Caen Normandie/Inserm U1075, Caen, France.

TNFα modulation has been reported to be either beneficial or detrimental in amyotrophic lateral sclerosis (ALS) and therefore appears as a key issue. We analysed the relationship between TNFα inhibitor (TNFi) exposure and ALS. We performed descriptive analysis of ALS reports in patients treated with TNFi, registered in the French Pharmacovigilance Database (FPvD) and disproportionality analyses by the 'case'/'non-case' method in FPvD and worldwide database (Vigibase ). The 8 retrieved ALS cases from the FPvD were 5 with limb-onset and 3 with bulbar-onset forms, in patients aged 43-75 years old, mainly treated for inflammatory rheumatism. The time to onset of the first symptoms ranged from 12 to 108 months, and the cumulative TNFi exposure before the diagnosis ranged from 12 to 120 months. TNFi was discontinued and thereafter survival ranged between 12 and 20 months. Disproportionality analyses showed significant associations between TNFi exposure and ALS in the FPvD and Vigibase (160 ALS cases), regardless comparators. A putative association between TNFi and ALS must be interpreted cautiously, but TNFi could act as a predisposing or risk factor. TNFi should therefore be avoided in patients with a known risk of ALS and discontinued in the case of neurological signs of ALS.
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http://dx.doi.org/10.1111/fcp.12480DOI Listing
December 2019

Does spontaneous adverse drug reactions' reporting differ between different reporters? A study in Toulouse Pharmacovigilance Centre.

Therapie 2019 Oct 31;74(5):521-525. Epub 2019 Mar 31.

Service de pharmacologie médicale et clinique, centre de pharmacovigilance, de pharmacoépidémiologie et d'informations sur le médicament, centre hospitalier universitaire, faculté de médecine, université de Toulouse, 37, allées Jules-Guesde, 31000 Toulouse, France. Electronic address:

Introduction: In France since 2011, report of adverse drug reactions (ADRs) has been extended to patients (and patients' associations) who can declare directly ADRs to their regional pharmacovigilance centre. In pharmacovigilance, informativeness of ADRs reports is important to improve signal's detection. The present study was performed to compare the quality of patients', physicians and community pharmacists' reports.

Methods: We performed a retrospective study investigating the quality of patients', physicians and community pharmacies' ADRs reported to Toulouse University PharmacoVigilance Centre (TUPVC) from January 2014 to June 2017. We used mandatory and non-mandatory criteria, as defined by European Medicines Agency. Reports' quality was defined as "satisfactory" when more than 90% of items were completed. We also compared reports' quality according to ADRs seriousness and the used reporting tools (email or the mobile app VigiBip).

Results: The number of reports to TUPVC increased between 2014 and 2016 (+51%) for patients and remained stable for pharmacists and physicians. According to the mandatory criteria, quality of the investigated reports was "satisfactory" (more than 90% of the items filled) whatever the reporter and without significant differences between reporters. For the non-mandatory criteria, clinical description of ADRs and ADRs' outcome were only filled over 90%. Significant differences were observed between the different reporters: community pharmacists informed better clinical description, ADR outcome and concomitant drugs versus both patients and physicians. Physicians informed better medical history and biological data whereas patients informed medical history and other aetiologies better than pharmacists and clinical description of ADRs better than physicians.

Conclusion: The present study failed to show differences between pharmacies', physicians' and patients' ADRs reports, for the mandatory criteria. However, significant differences were found for non-mandatory criteria with drug data more filled by pharmacists and medical ones more by physicians and patients.
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http://dx.doi.org/10.1016/j.therap.2019.01.008DOI Listing
October 2019

The French Levothyrox crisis: We did the best we could but….

Therapie 2019 Jun 19;74(3):431-435. Epub 2019 Jan 19.

Inserm, service de pharmacologie médicale et CRPV, université de Lille, CHU de Lille, 59045 Lille, France.

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http://dx.doi.org/10.1016/j.therap.2019.01.003DOI Listing
June 2019

Tintin in the Land of Drugs: A pharmacological, pharmacovigilance approach.

Therapie 2019 06 14;74(3):445-447. Epub 2019 Jan 14.

Service de Pharmacologie Médicale et Clinique, Centre de Pharmacovigilance, Pharmacoépidémiologie et d'Informations sur le Médicament, Faculté de Médecine, Centre Hospitalier Universitaire, 31000 Toulouse, France.

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http://dx.doi.org/10.1016/j.therap.2019.01.002DOI Listing
June 2019

Interest of pharmacoepidemiology for the study of anticoagulants.

Authors:
Haleh Bagheri

Therapie 2019 Apr 16;74(2):245-248. Epub 2019 Jan 16.

Inserm 1027, service de pharmacologie médicale et clinique, faculté de médecine, centre Midi-Pyrénées de pharmacovigilance de pharmaco-épidémiologie et d'informations sur le médicament, université de Toulouse, centre hospitalier universitaire de Toulouse, 31000 Toulouse, France. Electronic address:

Anticoagulants are essential for the treatment of cardiovascular illnesses. With the ageing population in the West countries, and the consequent increase in the frequency of thrombogenic heart diseases oral anticoagulants represent a not insignificant portion of drug consumption. Over the past few years, direct oral anticoagulants (DOACs) have been marketed because they are easier to use than vitamine K antagonists (VKAs). The introduction of these drugs has raised two main issues: (1) progress of the switch from VKAs to DOACs; (2) the comparison of adverse drug reactions (primarily hemorrhagic) on DOACs compared to indirect oral anticoagulants (IOAs). This article is confined to discussing oral anticoagulants, focusing on the two issues outlined above, and the potential answers that may be found in pharmacoepidemiology studies.
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http://dx.doi.org/10.1016/j.therap.2018.09.075DOI Listing
April 2019

Hypertension induced by serotonin reuptake inhibitors: analysis of two pharmacovigilance databases.

Fundam Clin Pharmacol 2019 Jun 11;33(3):296-302. Epub 2019 Jan 11.

Service de pharmacologie, UNICAEN, EA4650, CHU Caen Normandie, Normandie Université, Caen, 14000, France.

Drug-induced hypertension was described with several pharmacological classes, especially with serotonin reuptake inhibitors (SRIs). However, this link has remained controversial: the French summary of product characteristics specify a risk of hypertension only with paroxetine and sertraline. To identify a possible class effect common to all SRIs, our study investigated the reports of hypertension associated with SRIs in two pharmacovigilance databases. Two different types of investigations were performed: (i) a comparative study in VigiBase , which is the World Health Organization (WHO) pharmacovigilance database (PVDB), from where notifications of hypertension with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were extracted. The relationship between the suspected SRIs and the occurrence of hypertension was assessed by calculating reporting odds ratio (ROR) in a case/non-case design; (ii) a descriptive study of hypertension reports associated with SRIs in the French pharmacovigilance database (FPVDB). In VigiBase , 14 824 notifications of SRI-induced hypertension (2.5%) were identified (mean age 54.3 years, mainly women 69.1%). Among them, 3 879 (26.2%) were associated to sertraline; 3 118 (21.0%) to fluoxetine; 2 725 (18.4%) to paroxetine; 2 570 (17.3%) to citalopram; 2 295 (15.5%) to escitalopram; and 237 (1.6%) to fluvoxamine. A significant ROR value was found with all six SRIs (ROR range from 1.16 to 1.92). In the FPVDB, 24 reports of hypertension were found with all six SRIs used at standard doses, mainly in women (66.7%) with a mean age of 57.8 years and a median time of onset of 6 days. In 10 cases (42%), patients had a history of hypertension. This study, performed in real conditions of life, shows a significant pharmacovigilance safety signal between the use of SRIs and the development or worsening of hypertension.
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http://dx.doi.org/10.1111/fcp.12440DOI Listing
June 2019

Drug-Induced Anaphylaxis in a Vietnamese Pharmacovigilance Database: Trends and Specific Signals from a Disproportionality Analysis.

Drug Saf 2019 05;42(5):671-682

Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine de l'Université Paul-Sabatier (Medical and Clinical Pharmacology Laboratory, Faculty of Medicine, Paul-Sabatier University) and Centre Hospitalier Universitaire de Toulouse (Toulouse University Hospital Centre), Centre Midi-Pyrénées de PharmacoVigilance, de Pharmacoépidémiologie et d'Information sur le Médicament (Midi-Pyrenees Centre for Pharmacovigilance, Pharmacoepidemiology and Drug Information), UMR INSERM 1027, Toulouse, France.

Introduction: Despite the numerous studies investigating drug-induced anaphylaxis (DIA), understanding and quantitative data analysis in developing countries remain limited. The aim of our study is to describe and quantify DIA using the National Pharmacovigilance Database of Vietnam (NPDV).

Methods: Spontaneous reporting of adverse drug reactions (ADRs) recorded between 2010 and 2016 were retrospectively analysed to identify DIA reports. The trend and characteristics of DIA cases were described. Multivariate disproportionality analysis was used for signal generation.

Results: Overall, 4873 DIA cases (13.2% of total ADRs) were recorded in the NPDV, 111 of which resulted in death (82% of total ADR-induced deaths) over a 7-year period. There was a remarkable increase in DIA reporting over time (p < 0.001). The incidence rates of DIA reporting per total ADRs and per 100,000 inhabitants remained high (mean rates [95% CI] of 12.06 [9.88-14.24] and 0.77 [0.33-1.20], respectively). Concerning suspected drugs, systemic antibiotics (n = 3318, 68%) were mostly reported with a reporting odds ratio (ROR) and 95% CI of 2.35 [2.20-2.51]. In the case of antibiotic-induced anaphylaxis, the third-generation cephalosporins were predominant (n = 1961, 40.2%, ROR 2.39 [2.24-2.55]). We also noted drugs generally associated with DIA such as contrast agents (ROR 2.43 [2.04-2.88]) and anaesthetics (ROR 4.02 [3.30-4.89]). Furthermore, unexpected signals were observed for alpha-chymotrypsin (ROR 1.75 [1.23-2.44]) and amoxicillin/sulbactam (ROR 1.59 [1.18-2.10]), uncommonly reported in western countries.

Conclusion: In recent years, cases of drug-induced DIA have increased in Vietnam, mostly due to antibiotics and third-generation cephalosporins. The inappropriate use of these drugs should be taken into account. Our findings also highlighted typical Vietnamese signals for alpha-chymotrypsin- and amoxicillin/sulbactam-induced anaphylaxis, which may relate to a specific sociological context in resource-limited countries.
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http://dx.doi.org/10.1007/s40264-018-0758-8DOI Listing
May 2019

What is pharmacoepidemiology? Definition, methods, interest and clinical applications.

Therapie 2019 Apr 10;74(2):169-174. Epub 2018 Oct 10.

Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, Centre de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, UMR INSERM 1027, CIC INSERM 1436, Faculté de Médecine, Centre Hospitalier Universitaire, 31000 Toulouse, France.

Clinical evaluation of drugs before approval is based on the experimental design of clinical trial with randomization of drug exposure. Unfortunately, conclusions of clinical trials are necessarily limited to patients included into the trials. It is thus necessary to compare these experimental data coming from clinical trials with the real use of drugs in clinical practice. Pharmacoepidemiology is the study of interactions between drugs and human populations, investigating, in real conditions of life, benefits, risks and use of drugs. Pharmacoepidemiology applies to drugs the methods and/or reasoning of both pharmacology and epidemiology. The development of pharmacoepidemiology should improve the "rational drug use".
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http://dx.doi.org/10.1016/j.therap.2018.08.001DOI Listing
April 2019

Drug-induced bone loss: a major safety concern in Europe.

Expert Opin Drug Saf 2018 10 23;17(10):1005-1014. Epub 2018 Sep 23.

a Laboratoire de Pharmacologie Médicale et Clinique, Equipe de Pharmacoépidémiologie de l'UMR INSERM 1027, Faculté de Médecine de l'Université Paul-Sabatier et Centre Midi-Pyrénées de PharmacoVigilance , de Pharmacoépidémiologie et d'Information sur le Médicament de l'UMR INSERM 1027, Centre Hospitalier Universitaire , Toulouse , France.

Introduction: Drug-induced bone loss remains the major cause of vertebral and hip fractures and significantly associated to morbidity and mortality. This article will review the common drugs identified as the causes of bone loss and the risk factors and management in European countries.

Areas Covered: Beyond glucorticoid - the most cause of osteoporosis, many different drugs could cause harmful skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists, aromatase inhibitors are well-known cause of bone loss. Osteoporosis and fractures risk also increased with calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral anticoagulants, high doses of thyroxine and proton pump inhibitors.

Expert Opinion: Drugs are an important secondary cause of osteoporosis. Healthcare professionals should reassess the requirement for drugs and use the lowest dosage and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement, appropriate monitoring of bone status and initiating osteoporosis treatment if indicated are recommended when drugs having potential deleterious effects on bone are used, particularly in high risk patients. The update and further studies would provide concluded evidences of controversial drugs induced bone loss and determine the best prevention and treatment strategies.
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http://dx.doi.org/10.1080/14740338.2018.1524868DOI Listing
October 2018

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in vietnamese spontaneous adverse drug reaction database: A subgroup approach to disproportionality analysis.

J Clin Pharm Ther 2019 Feb 20;44(1):69-77. Epub 2018 Aug 20.

Laboratoire de Pharmacologie Médicale et Clinique (Medical and Clinical Pharmacology Laboratory), Faculté de Médecine de l'Université Paul-Sabatier (Faculty of Medicine, Paul-Sabatier University), Toulouse, France.

What Is Known And Objective: Despite the numerous studies investigating drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the understanding and quantitative data in developing countries remain limited. The study aimed to describe and quantify the drug-related risk of SJS/TEN in a resource-limited context using the Vietnamese spontaneous reporting database (VSRD) of adverse drug reactions.

Methods: Spontaneous reports relating to medium- and late-onset severe cutaneous adverse reactions (MLOSCAR) and SJS/TEN recorded in the VSRD from 2010 to 2015 were retrospectively analysed. The demographic characteristics and drug information were described and compared between SJS/TEN and other MLOSCAR reports. The drug-induced SJS/TEN signals were estimated using subgrouped disproportionality analysis with calculation of the reporting odds ratio (ROR) and the respective 95% confidence interval (CI).

Results: The VSRD received 2,849 MLOSCAR reports, 136 of which focus on SJS/TEN over a 6-year period. About 60% of SJS/TEN patients were male, and the majority of them were adults (mean age 42.5 ± 22.9). Up to 91.8% of drugs induced SJS/TEN within 1-28 days, and 45% SJS/TEN cases were evaluated as life-threatening. Positive signals were generated with carbamazepine (n = 25, ROR [95% CI] = 11.99 [7.07-19.92]), allopurinol (n = 15, ROR [95% CI] = 4.2 [2.20-7.59]), traditional/herbal medicines (n = 7, ROR [95% CI] = 2.76 [1.12-5.86]), colchicine (n = 4, ROR [95% CI] = 6.22 [1.69-18.72]), valproic acid (n = 3, ROR [95% CI] = 8.71 [1.89-30.19]) and meloxicam (n = 3, ROR [95% CI] = 7.09 [1.55-24.29]), which are well known for SJS/TEN. Cefixime (n = 5, ROR [95% CI] = 3.34 [1.13-8.00]) and paracetamol (n = 22, ROR [95% CI] = 5.23 [3.10-8.49]) also generated positive signals despite their popularity in Vietnam.

What Is New And Conclusion: This first Vietnamese population-based study has highlighted original characteristics and signals of drug-induced SJS/TEN, which are relatively consistent with other worldwide data and typical for a developing country.
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http://dx.doi.org/10.1111/jcpt.12754DOI Listing
February 2019