Aim The prescription of antipsychotic medication during pregnancy, particularly second‐generation antipsychotics, has increased in several countries in recent decades. This population‐based study investigated trends and patterns in antipsychotic medication use during pregnancy between 2011 and 2023 in Northern Ireland (NI), UK. The purpose was to improve understanding about how these medicines are used during pregnancy, including patterns of antipsychotic discontinuation across pregnancy. Methods Data from the Northern Ireland Maternity System (NIMATS) were linked to dispensed prescribing data from the Enhanced Prescribing Database (EPD) and the NI Multiple Deprivation Measure 2017 (NIMDM). Overall temporal trends were identified, and subsequently stratified by subtype (first‐ and second‐generation antipsychotics [FGAs and SGAs]). Usage was evaluated by pregnancy exposure period (12 weeks before pregnancy and by trimester). A separate analysis investigated patterns across trimesters in women who had been dispensed antipsychotics 12 weeks before pregnancy, including concomitant dispensing of antidepressants. Results The cohort included 287 757 singleton pregnancies in 175 938 women aged over 16 years, with an overall prevalence of antipsychotic use of 79.9 per 10 000 pregnancies. The prevalence of antipsychotic usage increased by 71% from 59 to 101 per 10 000 pregnancies between 2011 and 2023 ( p = .001). SGA usage almost tripled from 32 to 93 per 10 000 pregnancies, whereas FGA usage decreased by 73% from 30 to 8 per 10 000 pregnancies in 2011 compared with 2023. Overall usage of antipsychotics decreased across trimesters. Conclusion Overall antipsychotic prevalence during pregnancy increased over the study period, most notably SGA usage, whereas FGA usage decreased.
Background We conducted a systematic review of clinical trials and cohort studies on HIV post-exposure prophylaxis (PEP) regimens to inform updated 2025 Canadian guidelines.Methods We searched Medline and Embase (July 2017-June 2024) for studies reporting on: HIV acquisition, PEP completion, adverse events (AEs) leading to discontinuation and/or moderate to severe adverse events. Two reviewers independently screened abstracts and publications and extracted data from eligible articles.Results Of 5226 abstracts screened, we retrieved 112 full-text articles and included 22. Median study size was 160 (range = 52-26 988) participants. Regimens included DTG + TDF/XTC (n = 4, 18%), EVG/c/TDF/FTC (n = 4, 18%), BIC/TAF/FTC (n = 4, 18%), RAL + TDF/FTC (n = 4, 18%), EVG/c/TAF/FTC (n = 3, 14%), RPV/TDF/FTC (n = 2, 9%), DOR/TDF/FTC (n = 2, 9%), MVC + TDF/FTC (n = 1, 5%), a wide variety of protease inhibitor-based regimens (n = 7, 32%) and novel combinations with the injectable fusion inhibitor albuvirtide (n = 1, 5%); a third of studies included three or more regimens (n = 8, 36%). Among studies examining PEP completion rates (n = 12, 55%), cumulative completion rate was 86.6% (7779/8983 PEP episodes) and appeared highest for RAL + TDF/FTC, BIC/FTC/TAF and DOR/TDF/3TC at 96.4%, 96.3% and 95.0%, respectively. PEP tolerability was good, with few discontinuations due to adverse events; where data were available, this was lowest for INSTI-based regimens at 0.5% (pooled across two studies) for RAL + TDF/FTC, 1.0% (1/99) for DTG + TDF/XTC, 1.8% (2/109) for BIC/TAF/FTC and zero with albuvirtide (0/198). HIV seroconversions were rare (n = 5/8134, 0.06%) and often related to premature PEP discontinuation or repeated exposures.Conclusions Multiple PEP regimens have been associated with high completion, good tolerability and rare seroconversion, supporting their inclusion in clinical guidelines.
INTRODUCTION: The rapid uptake of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for obesity has been accompanied by increasing use outside approved indications and medical supervision. Evidence regarding the harms associated with such misuse remains limited because these situations are not captured in clinical trials and are difficult to identify in healthcare databases. METHODS: A nationwide pharmacovigilance study was performed on adverse drug reactions (ADRs) involving a GLP-1 receptor agonist or GLP-1/GIP co-agonist used in a misuse context and reported to the French pharmacovigilance system between January 2021 and January 2026. Misuse included inappropriate use outside approved indications, dosing recommendations, contraindications or medical supervision requirements. RESULTS: Seventy-two cases were identified, 58% of which were serious. Patients were predominantly female (83%) and young (median age 30 years), with five cases involving minors. Gastrointestinal disorders accounted for 77.7% of reports. Serious ADRs included acute pancreatitis (n = 9), paralytic ileus, gastroparesis, ketoacidosis and severe hypoglycaemia. Among cases with available dosing information, overdosing was involved in 76.4%. In nearly two-thirds of cases, drugs were obtained outside any medical framework through relatives, social media, online sources or the black market. More than half of all cases were reported during the final year of the study period. DISCUSSION: Misuse of GLP-1 RAs is increasing and is associated with serious but largely preventable harm. Unsupervised access, excessive dosing and use of unregulated products appear to be the principal drivers of risk. These findings support stronger measures to limit inappropriate access and improve risk communication regarding GLP-1 therapies.
Aims This study aimed to investigate the mechanisms and pharmacokinetic consequences of vincristine (VCR) drug–drug interactions (DDIs) with azole antifungals and dasatinib (DAS). Methods In vitro enzyme and transporter assays were conducted to characterize VCR metabolism and inhibition by posaconazole (POS), voriconazole (VRZ), fluconazole (FLZ) and DAS. Paediatric physiologically based pharmacokinetic (PBPK) models were developed using in vitro parameters and further refined using empirical Bayesian estimates from a VCR population pharmacokinetic model. Cytotoxicity was assessed using dorsal root ganglion (DRG) cell assays. Results POS competitively inhibited CYP3A4 and CYP3A5 ( Kᵢ = 1.62 and 1.35 μM) and P‐gp ( IC 50 = 7.72 μM), whereas VRZ competitively inhibited CYP3A4 and CYP3A5 ( Kᵢ = 8.87 and 4.22 μM) and additionally exhibited mechanism‐based inhibition of CYP3A4 (K I = 16.24 μM, k inact = 0.0263 min −1 ). FLZ showed weak inhibition of CYP3A4 and CYP3A5 (Kᵢ > 60 μM), whereas DAS showed moderate inhibition ( Kᵢ = 1.99–4.42 μM). The simulated VCR clearance was also approximately halved (CL = 0.59 vs . 0.33 L/h/kg) when co‐administrated with POS. Moreover, PBPK modelling indicated that intravenous POS and VRZ increased VCR AUCs by more than twofold. In vitro DRG cell assays demonstrated a concentration‐dependent potentiation of VCR‐induced cytotoxicity by POS. Conclusions Collectively, these PBPK model predictions suggest that POS and VRZ may represent high‐risk perpetrators of VCR DDIs in children and may help guide future dose optimization and toxicity management, pending confirmation in prospective clinical studies.
Aim To systematically evaluate the safety of proton pump inhibitor (PPI) therapy in children aged 0–12 years, with a focus on treatment‐emergent adverse events across different study designs and age groups. Method The systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, Scopus, Google Scholar and Grey literature sources. Eligible studies included retrospective cohort studies, randomized controlled trials and phase 1/early‐phase studies. Data extraction focused on reported adverse events, patient age, drug type and treatment duration. The methodological quality was assessed using study‐design‐specific tools. Randomized controlled trials were evaluated with the Cochrane Risk of Bias 2.0 (RoB 2) tool, observational cohort studies with the Newcastle–Ottawa Scale (NOS) and non‐randomized interventional studies with the Methodological Index for Non‐Randomized Studies (MINORS). Conclusion Short‐term PPI use in children appears generally safe, with predominantly mild gastrointestinal and respiratory adverse events. Serious complications are uncommon but may be underestimated due to limited follow‐up and inconsistent reporting. Use of PPIs in infants with physiological reflux is discouraged, as gastric contents are typically non‐acidic due to milk buffering.
