Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

PURPOSE/BACKGROUND: Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. METHODS/PROCEDURES: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. FINDINGS/RESULTS: The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. IMPLICATIONS/CONCLUSIONS: This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

Four cases of audio-vestibular disorders related to immunisation with SARS-CoV-2 mRNA vaccines.

OBJECTIVE: To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines. DESIGN: Case description. STUDY SAMPLE: We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech®) and mRNA-1273 (Moderna®) vaccines. RESULTS: Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement. CONCLUSIONS: The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2.

[Pharmacovigilance - mRNA COVID-19 vaccines : current state of knowledge on their adverse effects]. / Pharmacovigilance - Vaccins à ARNm contre le Covid-19 : le point sur les effets indésirables.

The COVID-19 pandemic has stimulated the rapid development and large-scale use of technologically innovative vaccines, such as the mRNA vaccines Spikevax (Moderna) and Comirnaty (Pfizer-BioNTech). This unprecedented deployment has challenged pharmacovigilance, requiring combined skills in safety monitoring, prompt data analysis and continuous dissemination of knowledge. Main recognised adverse events of these vaccines are moderate and transient, linked to their significant reactogenicity. Active post-marketing surveillance has identified rare adverse events such as myopericarditis and a variety of skin reactions. A number of potential rare adverse events are being evaluated and could be retained at the individual level, but do not question the overall safety of these vaccines.

La pandémie de Covid-19 a conduit au développement rapide de vaccins à la technologie innovante, utilisés à large échelle, dont les vaccins à ARNm Spikevax (Moderna) et Comirnaty (Pfizer-BioNTech). Ce déploiement sans précédent défie la pharmacovigilance, nécessitant d'allier un suivi attentif de la sécurité, une analyse rapide des données et une diffusion continue des connaissances. Les principaux effets indésirables reconnus pour ces vaccins sont modérés et transitoires, liés à leur importante réactogénicité. Une pharmacovigilance active a permis d'identifier des effets indésirables rares, tels que des myopéricardites et diverses réactions cutanées. Un certain nombre d'effets indésirables rares potentiels sont en cours d'évaluation et pourraient être retenus à l'échelle individuelle, mais ne remettent pas en cause la sécurité vaccinale globale.

[Pharmacovigilance update]. / Pharmacovigilance.

The main pharmacovigilance updates in 2020 are reviewed. Remdesivir in COVID-19: relatively safe but turns out to be less effective than expected. Hydroxychloroquine in COVID-19 : lack of efficacy and risk of arrhythmias. Cytokines storm in COVID-19: may impact pharmacokinetics. VEGF inhibitors: risk of aneurysm and artery dissection. Tofacitinib: dose-dependant risk of venous thromboembolic events. Ondansetron in the first trimester of pregnancy : a highly debated risk of orofacial cleft defects. Fingolimod : contraindicated during pregnancy due to suspected risk of congenital malformations. Ranitidine: global market withdrawal due to contamination with nitrosamines. Ulipristal for uterine fibroids : market withdrawal due to risk of severe liver injury. Ingenol mebutate : market withdrawal due to paradoxical risk of skin cancers.

Les principales actualités de pharmacovigilance 2020 sont passées en revue. Remdésivir et Covid-19 : moins efficace qu'attendu mais assez sûr. Hydroxychloroquine et Covid-19 : absence d'efficacité et risque d'arythmies. Orage cytokinique et Covid-19 : impact possible sur les paramètres pharmacocinétiques. Inhibiteurs du VEGF : risque d'anévrisme artériel et de dissection. Tofacitinib : risque d'événements thromboemboliques. Ondansétron au 1er trimestre de grossesse : risque controversé de fentes palatines. Fingolimod : contre-indiqué dans la grossesse pour possible risque malformatif. Ranitidine : retrait du marché mondial pour contamination par des nitrosamines. Ulipristal et fibromyomes utérins : retrait du marché pour risque d'atteinte hépatique grave. Mébutate d'ingénol : retrait du marché pour risque paradoxal de cancers cutanés.