Aim. Pregnant women require different nutritional intake such as folic acid, iron and cholecalciferol, and specific vaccination to prevent fetal abnormalities and improve outcomes.. This study aims to analyze usage trends for these recommended drugs over the last decade, and to identify maternal factors associated with their use. Methods. The nationwide cross-sectional study is based on data from the French national administrative health database, including pregnancies from 2012 to 2022. Folic acid, iron, cholecalciferol, and influenza vaccination use were analyzed according to the relevant periods based on WHO and French guidelines. Multivariable logistic regression assessed maternal characteristics associated with drug use. Results. Analyzing 8,979,173 pregnancies, the study found that 46.0% of pregnancies used folic acid during the periconceptional period, rising from 33.8% in 2012 to 52.6% in 2022. Women with chronic disease and higher financial resources were more likely to use it. 64.1% used iron during pregnancy with exposure increasing with age. 35.5% used cholecalciferol, with higher socioeconomic status associated with increased use. Only 5.1% were vaccinated against influenza, with the rate increasing until 2020, before declining. Vaccination was positively associated with maternal age, the presence of a chronic disease, and higher financial resources. Conclusion. This study revealed increasing trends of use in recommended drugs during pregnancy over the last decade, although overall prevalence remains not optimal, and concerning for influenza vaccination. The identified risk factors for non-use include young maternal age, low income, and deprived areas, emphasizing the need for targeted interventions to improve maternal health outcomes.

This case report describes of a pharmacokinetic drug–drug interaction between crizotinib, a tyrosine kinase inhibitor, and sofosbuvir/velpatasvir, a direct-acting antiviral drug, leading to cardiac toxicity. A 75-year-old man, with no cardiovascular history but a diagnosis of metastatic non-small cell lung cancer with MET exon-14 deletion and hepatitis C virus infection genotype 1A, received both crizotinib and sofosbuvir/velpatasvir. Crizotinib was well tolerated, but 1 week after sofosbuvir/velpatasvir initiation, the patient experienced bilateral lower-limb edema and class III NYHA dyspnea. We assumed that increased exposure to crizotinib could account for this cardiac toxicity. Drug causality was probable according to the Naranjo scale. We hypothesized a reciprocal interaction between crizotinib and velpatasvir, mediated by both cytochrome 3A4 (CYP3A4) and P-glycoprotein (P-gp). Clinicians should be aware of the risk of drug–drug interactions between direct-acting antiviral agents that inhibit CYP3A4 (glecaprevir) and/or P-gp (voxilaprevir) and anticancer tyrosine kinase inhibitors that are mostly CYP3A4 and/or P-gp substrates (gefitinib, afatinib, erlotinib, crizotinib, ceritinib, lorlatinib, brigatinib, capmatinib etc.).

Several cases of herpes zoster (HZ) following mRNA COVID-19 vaccination (BNT162b2 and mRNA-1273) have been reported, and first epidemiological evidences suggest an increased risk. We used the worldwide pharmacovigilance database VigiBase to describe HZ cases following mRNA COVID-19 vaccination. We performed disproportionality analyses (case/non-case statistical approach) to assess the relative risk of HZ reporting in mRNA COVID-19 vaccine recipients compared to influenza vaccine recipients and according to patient age. Until 30th June 2021, of 716,928 reports about mRNA COVID-19 vaccines, we found 7,728 HZ cases. When compared to influenza vaccines, mRNA COVID-19 vaccines were associated with a significantly higher reporting of HZ (reporting odds-ratio 1.9, 95%CI [1.8-2.1]). Furthermore, we found a reduced risk of reporting HZ among under 40 year-old persons compared to older persons (reporting odds-ratio 0.39, 95%CI [0.36-0.41]). For the first time, we could assess at a global level the risk of HZ after mRNA COVID-19 vaccination.

Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regards to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population specific factors (e.g. more frequent use of off-label/unlicensed drugs). In recognition of these challenges a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life-cycle of medicinal products which is described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development and safety data collection and analysis. Furthermore, they describe the specific details of post-marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record-linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit-risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life-cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs.