The enhanced national pharmacovigilance system implemented for COVID-19 vaccines in France: A 2-year experience report.

In March 2020, World Health Organization recognized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence as a public health emergency of international concern. One of the major preventative measures developed against coronavirus disease 2019 (COVID-19) was vaccines. To monitor their use and safety of vaccines from the first utilization in humans during clinical development phases to implementation for the general population, an enhanced national pharmacovigilance system was enabled by the French National Agency for Medicines and Health Products Safety in collaboration with the 30 Regional Pharmacovigilance Centres.

COVACPREG, a French prospective cohort study of women vaccinated against COVID-19 during pregnancy.

The objective of this cohort study was to describe the French population of pregnant women vaccinated against coronavirus disease 2019 (COVID-19), their pregnancy outcomes and the health status of their newborns (malformation rate, neonatal diseases, etc.), and to proactively collect and analyze reported adverse reactions over time. We conducted a prospective study using an online questionnaire.

Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis.

Background: Lamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes.

Methods: All comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched.

Risk of drug use during pregnancy: master protocol for living systematic reviews and meta-analyses performed in the metaPreg project.

Background: Knowledge about the risks of drugs during pregnancy is continuously evolving due to the frequent publication of a large number of epidemiological studies. Systematic reviews and meta-analyses therefore need to be regularly updated to reflect these advances. To improve dissemination of this updated information, we developed an initiative of real-time full-scale living meta-analyses relying on an open online dissemination platform ( www.

Use of proton pump inhibitors during pregnancy: A systematic review and meta-analysis of congenital malformations.

Use of proton pump inhibitors (PPI) are common among pregnant women to relieve gastrointestinal symptoms. The number of exposed pregnancies is therefore considerable, and a recent meta-analysis (MA) from 2020 raised concern about their teratogenicity. The aim of the study was to provide a MA of the risk of major congenital malformations (MCM) after PPI exposure during the first trimester of pregnancy.

Safety Signal Generation for Sudden Sensorineural Hearing Loss Following Messenger RNA COVID-19 Vaccination: Postmarketing Surveillance Using the French Pharmacovigilance Spontaneous Reporting Database.

Background: The World Health Organization recently described sudden sensorineural hearing loss (SSNHL) as a possible adverse effect of COVID-19 vaccines. Recent discordant pharmacoepidemiologic studies invite robust clinical investigations of SSNHL after COVID-19 messenger RNA (mRNA) vaccines. This postmarketing surveillance study, overseen by French public health authorities, is the first to clinically document postvaccination SSNHL and examine the role of potential risk factors.

Adverse drug reactions in pregnant women: Do they differ from those in non-pregnant women of childbearing age?

Pharmacoepidemiological research in pregnant women has focused on adverse drug reactions for the course of pregnancy or for the unborn child, but little is known on the risks for the mother. We reported the results of a study that compared adverse drug reactions in pregnant women with non-pregnant women of childbearing age, and investigated whether which types of adverse reactions were more often reported in pregnant women and which drugs were more often involved. This study was carried out in the French pharmacovigilance database (BNPV).

SGLT2 inhibitors in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials balancing their risks and benefits.

Aims/hypothesis: Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have been reported. The risk/benefit ratio of SGLT2i remains unquantified.

Adverse drug reactions associated with immune checkpoint inhibitors: An exploratory nested case-control study in a historical cohort.

Introduction: Data on adverse drug reactions (ADRs) of immune checkpoint inhibitors (ICIs) used in oncology are mainly derived from clinical trials or cancer-specific reviews. We aim to analyze ADRs that occurred in patients treated with ICIs in real life.

Materials And Methods: We conducted an observational study on a historical cohort of the University Hospitals of Lyon.

Feasibility study and evaluation of expert opinion on the semi-automated meta-analysis and the conventional meta-analysis.

Purpose: To assess the feasibility and acceptance of the semi-automated meta-analysis (SAMA). The objectives are twofold, namely (1) to compare expert opinion on the quality of protocols, methods, and results of one conventional meta-analysis (CMA) and one SAMA and (2) to compare the time to execute the CMA and the SAMA.

Methods: Experts evaluated the protocols and manuscripts/reports of the CMA and SAMA conducted independently on the safety of metronidazole in pregnancy.

Pregnancy outcome following first-trimester exposure to fingolimod: A collaborative ENTIS study.

This prospective multicentre cohort study investigated pregnancy outcomes after fingolimod use for multiple sclerosis during pregnancy. Pregnancy outcomes of 63 fingolimod and 62 interferon-β-exposed pregnancies were compared. Rates of major congenital anomalies (MCA) were 4.

Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis.

Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta-analytic approach. MEDLINE, ClinicalTrials.

Methylprednisolone-related liver injury: A descriptive study using the French pharmacovigilance database.

Purpose: Hepatotoxicity associated with methylprednisolone (MP) is rarely reported in the literature. The aim of the present study was to review the characteristics of acute liver injury associated with intravenous (IV) or oral MP registered in the French pharmacovigilance database (FPD).

Methods: All cases with MP coded as suspected, concomitant, or interacting drug associated with liver injury as the adverse effect reported up to May 2016 were extracted from the FPD.

Spontaneous multiple cervical artery dissections after alemtuzumab.

We report a case of multiple cervical artery dissections that occurred 4 days after a first course of alemtuzumab in a woman with relapsing-remitting multiple sclerosis and discuss its potential relationship and mechanisms of action. In particular, an arterial inflammatory process, secondary to cytokine release, could potentially lead to intimal thickening, luminal irregularities, stenosis, and ultimately occlusion. Occurrence of an unexpected serious adverse event, in our case, multiple cervical artery dissections, especially in a close time window after drug administration, questions a potential causal relationship with the drug or a simple coincidence.

Pregnancy outcomes in women exposed to cancer chemotherapy.

Purpose: There is little data on the effects of cancer chemotherapy in pregnant women. The objective of this study was to describe pregnancy outcomes of women exposed to cancer chemotherapy, recorded in the French Terappel database.

Methods: We performed a descriptive, prospective study of the pregnancies of women exposed to cancer chemotherapy recorded in Terappel between June 1984 and December 2016.

Antituberculosis Drug-Associated DRESS: A Case Series.

Background: Although antituberculosis drug-associated drug reaction with eosinophilia and systemic symptoms (DRESS) is rarely reported, its diagnosis should not be dismissed. Its management implies an early withdrawal of suspected drugs.

Objective: The objective of this study was to describe the characteristics of antituberculosis drug-associated DRESS and to identify the most likely involved drugs.

Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

Introduction: Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding.

Aim: We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding.

Methylprednisolone liver toxicity: A new case and a French regional pharmacovigilance survey.

Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded.

Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database.

Introduction: Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database.

Methods: The national MedDRA database was searched using the term "angioedema".

Safety profile of etifoxine: A French pharmacovigilance survey.

Etifoxine chlorhydrate is a benzoxazine derivative approved for the treatment of psychosomatic manifestations of anxiety since 1979. Previously labeled adverse drug reactions (ADRs) only include drowsiness, benign cutaneous reactions, and acute hypersensitivity reactions. The objectives were to examine recent data on etifoxine-related ADR by reviewing Individual Case Safety Reports (ICSRs) recorded in France especially unexpected ADRs.

Serotonin Syndrome: Analysis of Cases Registered in the French Pharmacovigilance Database.

Background: More information would be required for a better understanding of the actual circumstances of serotonin syndrome (SS) occurrence in routine clinical practice.

Aim: The objective of the study was to analyze characteristics of SS French pharmacovigilance reports, especially involved drugs and nature of drug-drug interactions (DDIs).

Method: We performed a retrospective analysis of SS registered in the French pharmacovigilance database between January 1, 1985 and May 27, 2013.