Risk of hospitalization for adverse drug events in women and men: A post hoc analysis of an active pharmacovigilance study in italian emergency departments

This post hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visits and hospitalization in women and men. During the study period (January 2007–December 2018), 61,855 reports of ADEs leading to ED visits were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13–176), antidepressants (ROR 1.12, CI 1.03–1.23) and antidiabetics (ROR 1.13, CI 1.02–1.24). Among men, only vitamin K antagonists (ROR 1.28, CI 1.09–1.50), opioids (ROR 1.30, CI 1.06–1.60) and digitalis glycosides (ROR 1.32, CI 1.09–1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidities were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing an adverse event following immunization (ROR 0.36, CI 0.27–0.48 and 0.83, 0.42–0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes

Drug-Related Hypersensitivity Reactions Leading to Emergency Department: Original Data and Systematic Review

The aim of the present study is to describe pharmacological characteristics of drug-related allergies and anaphylaxis leading to the emergency department (ED). An 8-year post hoc analysis on the MEREAFaPS Study database was performed (2012–2019). Subjects who experienced drug-related hypersensitivity leading to an ED visit were selected. Logistic regression analyses were used to estimate the reporting odds ratios (RORs) of drug-related allergies and anaphylaxis adjusting for sex, age classes, and ethnicity. In addition, a systematic review of observational studies evaluating drug-related hypersensitivity reactions leading to ED visits in outpatients was performed. Out of 94,073 ED visits, 14.4% cases were drug-related allergies and 0.6% were anaphylaxis. Females accounted for 56%. Multivariate logistic regression showed a higher risk of drug-related allergy among males and all age classes < 65 years, while a higher risk of anaphylaxis was observed for females (ROR 1.20 [1.01–1.42]) and adults (ROR 2.63 [2.21–3.14]). The systematic review included 37 studies. ED visits related to allergy and anaphylaxis ranged from 0.004% to 88%, and drug-related allergies and anaphylaxis ranged from 0.007% to 88%. Both in our analysis and in primary studies, antibacterials, analgesics, and radiocontrast agents were identified as the most common triggers of hypersensitivity

Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study

Background: Erythropoiesis-stimulating agents (ESAs) are biological molecules approved for the treatment of anemia associated with chronic renal failure. Biosimilars were licensed for use in Europe in 2007. Aim: This study aimed to compare the safety profile of biosimilars with respect to the reference product in a nephrology setting. Methods: A prospective study was conducted in four Italian regions between 1 October 2013 and 30 June 2015. The study population included patients aged 65 18&nbsp;years undergoing hemodialysis and treated with epoetins as per the clinical practice of the participating centers. The two comparison cohorts included patients treated with either an originator or a biosimilar epoetin alfa. Each patient was followed up until occurrence of any safety outcome of interest (grouped into three major categories), switch to a different ESA product, transplant or peritoneal dialysis, death, or end of the study period, whichever came first. Results: Overall, 867 subjects were included in the study (originator: N = 423; biosimilar: N = 444). Biosimilar users were older than originator users (median age of 76 vs 64&nbsp;years, respectively), more frequently affected by arrhythmia (29.3 vs 22.5%), and less frequently candidates for transplantation (3.8 vs 18.2%). Cox-regression analysis showed no increase in risk of safety outcomes in biosimilar users, even after adjusting for confounding factors: 1.0 (95% confidence interval [CI] 0.7\u20131.3) for any outcomes; 1.1 (95% CI 0.7\u20131.8) for problems related to dialysis device; 0.9 (95% CI 0.6\u20131.5) for cardio- and cerebro-vascular conditions; 0.9 (95% CI 0.6\u20131.5) for infections. Conclusion: This study confirms the comparable safety profiles of originator and biosimilar epoetin alfa drugs when used in patients receiving dialysis

Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case–control study

Only three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs

When important steps for a reliable meta-analysis are missing: the bevacizumab versus ranibizumab case

letter to the edito

Dronedarone-associated acute renal failure: evidence coming from the Italian spontaneous ADR reporting database

AIM To describe cases of acute renal failure (ARF) and of renal failure (RF) from dronedarone retrieved in the general population during post-marketing surveillance through the Italian spontaneous ADR reporting database. METHODS A case by case analysis was performed. Reports codified with the System Organ Class (SOC) term \u2018urinary system disorders\u2019 of the ADR terminology of the World Health Organization associated with dronedarone treatment were selected. RESULTS Out of 124 069 ADR reports, in 55 of them dronedarone was listed as the suspected drug. Among these reports, we identified four cases of ARF, two of RF and three cases of increase of blood creatinine submitted by physicians between October 2010 and December 2011. The patient age was from 61 to 84 years and most cases occurred within the first 13 days of initiation of dronedarone therapy (range 6 days \u2013 2 months). Only one patient received a co-suspected drug labelled for causing ARF. In all reports but one, positive dechallenge was reported. CONCLUSIONS Clinicians should be made aware of the risk of ARF/RF associated with dronedarone and of the need to screen patients appropriately for ARF/RF risk factors before starting dronedarone therapy

Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions

Aim: Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Methods: Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P \ue2\u89\ua4\uc2\ua00.05 were statistically significant. Results: We retrieved 32\uc2\ua0972 reports. We identified 204 ADRs with a ROR >1 (P \ue2\u89\ua4\uc2\ua00.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47\ue2\u80\u931.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28\ue2\u80\u930.34)]. We identified other potential signals that have not been associated with DOACs previously. Conclusions: As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred

Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case-control study

Only three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs

Studio osservazionale comparativo del profilo di sicurezza delle formulazioni di tiotropio

Introduzione. Le Linee Guida per il trattamento della Broncopneumopatia Cronica Ostruttiva (BPCO) prevedono l’utilizzo di farmaci broncodilatatori e, tra questi, degli anticolinergici a lunga durata d’azione. Il tiotropio è il farmaco maggiormente utilizzato e in Italia sono in commercio due device: Handihaler® (dal 2004) e Respimat® (dal 2011). Le evidenze disponibili negli ultimi anni hanno fatto nascere dubbi sul profilo di sicurezza della formulazione Respimat®. Le differenze tra le popolazioni che utilizzano il farmaco nella normale pratica clinica e quelle incluse nei trial clinici potrebbero spiegare i risultati contrastanti tra gli RCT e gli studi osservazionali. Per verificare il segnale di rischio di malattie cardiovascolari, cerebrovascolari e disturbi del ritmo cardiaco è stato condotto uno studio di coorte retrospettivo tra gli utilizzatori incidenti di tiotropio Handihaler® e Respimat® nel periodo 2011-2013, nelle Regioni Lombardia e Umbria. Metodi. Le coorti sono state identificate attraverso le prescrizioni farmaceutiche SSN, che comprende l’erogazione attraverso le farmacie, la distribuzione diretta e per conto. Le informazioni sulle comorbidità e sugli esiti clinici sono state ottenute dalle Schede di Dimissione Ospedaliera (SDO). Gli eventi sono rappresentati da un ricovero per infarto del miocardio e/o per disturbi del ritmo cardiaco nel periodo di esposizione corrente (definito, a partire dalla data di prescrizione, come somma delle DDD più 15 giorni). Ogni soggetto è stato seguito dalla prima prescrizione di tiotropio fino alla prima delle seguenti date: fine del periodo di esposizione; passaggio da una formulazione di tiotropio all’altra (switch); ricovero per uno degli eventi in studio nel periodo corrente; fine dello studio (31.12.2013). Risultati. Sono stati identificati 120.434 soggetti con prescrizione incidente di tiotropio (77% Handihaler® e 23% Respimat®), con un'età media di 73 anni e un rapporto uomini/donne di 1,3. I due gruppi presentavano percentuali diverse nella maggior parte delle comorbidità e dell'uso di farmaci; le patologie più frequenti sono risultate tumori, malattie respiratorie, scompenso cardiaco, malattie cerebrovascolari, diabete e ipertensione. Sono stati osservati 645 eventi durante 159.589 mesi di esposizione corrente di Handihaler® (incidenza: 4,0 per 1.000 mesi persona) e 152 eventi durante 42.965 mesi del Respimat® (incidenza: 6,5 per 1.000 mesi persona). L'hazard ratio, Respimat® vs Handihaler®, è risultato pari a 0,86 (IC 95%: 0,72-1,02). Conclusioni. Questo studio su una popolazione di grande dimensioni, consente di fornire un ulteriore contributo alla valutazione della sicurezza d'uso delle formulazioni di tiotropio