National Pharmacovigilance Network Research Articles

Adverse events following Measles-Mumps-Rubella and varicella immunization: A safety profile analysis and comparison of different vaccination schedules based on the Italian Pharmacovigilance Network in the Veneto Region

ObjectiveThe vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored. MethodsWe identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022. Results9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V. ConclusionPassive surveillance data show a significantly higher rate of serious events for males 0–2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations.

Single-centre descriptive study of adverse events reported after anti-COVID vaccination

Introduction: In Italy, approximately 80.5% of the population has completed the primary anti-COVID vaccination cycle with approximately 141 million doses administered. With the introduction of new measures to counter the spread of COVID-19, including compulsory vaccination for certain categories of people, the population expressed fears about the safety and adverse effects of SARS-CoV-2 vaccines. Several factors, such as gender and age, could have influenced the outcomes associated with the vaccine. Our single-centre work seeks to provide such evidence with respect to Pfizer/BioNTech’s BNT162b2 (Comirnaty) and AstraZeneca’s AZD1222 (Vaxzevria) vaccines. Materials and Methods: Single-centre descriptive study carried out on a sample of subjects who underwent anti-COVID vaccination at the ‘San Giovanni di Dio e Ruggi d’Aragona’ AOU vaccination centre in Salerno. Patients who reported a suspected adverse reaction after receiving a dose of vaccine were included in the study. The regional vaccine platform SORESA and the VigiFarmaco portal were used to collect the data. Results: During the period covered by the study, 126,928 doses of SARS-CoV-2 vaccine were administered. The Pfizer-BioNTech vaccine group comprised 124,138 administrations. The AstraZeneca vaccine group consisted of 2,790 administrations. 287 post-vaccination adverse reaction reports entered in the National Pharmacovigilance Network were considered. In most of the reactions reported, for both vaccines considered, the symptomatology was attributable to local reactions at the injection site. At the systemic level, however, we noted the prevalence of non-specific events such as fever, headache and diffuse arthromyalgia. Conclusions: Based on our results and comparison with the literature, the data collected on the vaccines considered in the study suggest a favourable safety profile for their large-scale use. The rate of minor adverse events turned out to be low, with similarly reassuring data compared to serious adverse events, such as not to justify hesitation towards vaccination for COVID-19 disease control.

Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network.

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

A retrospective pharmacovigilance analysis: could decreased reporting of suspected adverse reactions generate future safety concerns?

The collection and management of spontaneous reports of suspected adverse drug reactions represents a passive pharmacovigilance method for post-marketing drug safety surveillance, as it is a practical and rapid way to detect a potential warning sign. We performed an in-depth retrospective analysis of suspected adverse reaction reports in the National Pharmacovigilance Network (RNF) for the first eight months of 2019 (pre-pandemic period), 2020 (global pandemic covid-19 onset), 2021 (first post-pandemic period due to vaccine phase). The reports of suspected adverse drug reactions were extrapolated from the National Network of Pharmacovigilance. Data from Italy, the Campania Region, and the Local Health Unit Naples 3 South were compared. A retrospective qualitative analysis of demographics data, clinical status, suspected drugs, adverse drug reactions (ADRs) description and its degree of seriousness were collected. We observed 1071 ADRs, of which 281 were serious; of these, 39 led to hospitalization, 779 were not serious, and 2 caused death. In the pre-pandemic period, chemotherapy drugs most frequently induced ADRs. The year 2020, in the midst of the covid-19 pandemic, saw a clear reduction in the number of drug reports, compared to 2019 and 2021, both at national and regional level, and at ASL Napoli 3 Sud. A reduction in 2020 that ranges from -40.75% to -72.56% at the national and regional level, respectively; reaching as much as -88.13% at the local level in the health authority under analysis. In 2021, on the other hand, there is a clear increase in the number of reports, which numerically exceed even those in 2019 by +194.71% in Italy, +15.25% in the Campania Region, and +90.68% in the Local Health Unit Naples 3 South. The covid-19 pandemic has affected the trend in the number of reports of suspected adverse drug reactions. This is for several reasons: first, frontline exposed health care workers have been able to devote less time to pharmacovigilance activities to cope with the health emergency, second, since the start of the covid-19 vaccination campaign, health care workers have been more focused on reporting suspected adverse reactions to vaccines. Clinicians should beware of these adverse effects and monitor early warning signs carefully.

Postmarketing surveillance of adverse events following meningococcal B vaccination: data from Apulia Region, 2014–19

ABSTRACT Since the multicomponent meningococcal B vaccine introduction, the Apulian Regional Health Authority implemented postmarketing surveillance program, as provided by Italian laws. From National Pharmacovigilance Network, we selected 4CMenB AEFIs reported in Apulia from 01 January 2014 to 31 December 2019, while the number of 4 cMen B doses administered per year was obtained from the regional immunization database (GIAVA). For each subject who experienced an adverse event following meningococcal B vaccine (AEFIs), a predefined form was filled in. A total of 214 AEFIs (26.5 × 100.000 doses) were reported after any dose of MenB-4 c vaccination of which 58/214 (27.1%) were classified as serious (7.2 × 100,000 doses), 145/214 (67.8%) as not serious (180 × 100,000 doses), and 11/214 (5.1%) as undefined (1.3 × 100,000 doses). The average age of subjects who experimented and AEFI was 30 months. The majority of serious AEFIs were reported in 2- to 11-month-old children (44/57; 77.2%). A total of 31/58 (3.8 × 100,000 doses; 53.4%) serious AEFIs were reported as having a ‘consistent causal association’ with vaccination. Of these, fever/hyperpyrexia was reported in 21/31 (2.6 × 100,000 doses; 67.7%); hypotonic-hyporesponsive episode was reported in 7/31 (0.9 × 100,000 doses [add %-age]) and was the most frequent adverse event with neurological symptoms. A total of 13/31 (41.9%) serious AEFIs classified as ‘consistent causal association’ were reported after the first dose of 4cMenB, of these 5/13 (38.5%) children did not complete the vaccination schedule. Our data seemed to confirm, in a large population, the a good safety profile of the universal mass vaccination with 4CMENB.

Fatal hepatotoxicity due to sevoflurane use in a paediatric patient after aortic repair: reality or fiction? A case of pharmacovigilance

Hepatotoxicity secondary to exposure of volatile anaesthetics is an exceptional finding, but its clinical interest depends on their frequent use, unpredictable appearance and potential severity. Halothane is the volatile anaesthetic...

Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem

The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19.Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious.Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%.These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly.

Suspected adverse drug reactions (ADRs) trends in older Italianpatients: an analysis from the National Pharmacovigilance Network.

The clinical management of older populations is a social and clinical challenge. These subjects are more vulnerable to adverse drug reactions (ADRs) due to multi morbidity, polypharmacy, and physio-pathological changes. We performed a study using data from the National Network of Pharmacovigilance of Italy available from 2001 to 2012, which include all spontaneous reports of suspected ADRs. Our study showed that 29,036 reports of suspected ADRs were recorded in 2012. Those for patients aged ≥ 65years were 11,426 that correspond to a reporting rate of 923.6 reports per million inhabitants. On the contrary, the reporting rate for total population was of 489 reports per million inhabitants. The evaluation of level of severity showed that 37% of reports of suspected ADRs in patients aged ≥ 65years were serious compared to 30% in the general population. Furthermore, 27% of reports recorded for older patients showed that they required more hospitalization or long-term care in comparison with the 21% for the general population, with a relevant impact on National Health Service costs. These data suggest the need to optimize the clinical strategy for older patients due to the multiple factors that increase the susceptibility to ADRs. There is a high need to potentiate clinical trials on older patients to adopt new diagnostic-therapeutic pathways in real life.

Report of Adverse Events in Colombia: A Successful Case.

The Colombian National Food and Drug Surveillance Institute (INVIMA) is responsible for monitoring the safety and efficacy of medicines circulating the Colombian market. This article summarizes the three key strategies the institution has implemented to strengthen the National Pharmacovigilance Program: improving the interaction and working relationship with regional health authorities, expanding the National Pharmacovigilance Network and implementing the electronic submission of adverse events. The number of adverse events reported in Colombia increased from 5,447 in 2013 to 95,658 in 2017, reaching a population-based reporting ratio within international standards (563 in 2016).

Evaluation of adverse drug reactions associated with direct oral anticoagulants recorded in the Italian Pharmacovigilance Network database using a specifically developed risk index

The introduction into clinical practice of direct oral anticoagulants (DOAC) has widened the scenario in the prevention and treatment of thromboembolism. However, the evaluation of the balance between the thrombotic and hemorrhagic risks is a critical issue in the choice of an oral anticoagulant agent. The availability of safety and efficacy data for each drug represents the basis to operate treatment choices. As there are no head-to-head studies comparing the different DOACs in terms of safety and efficacy, and considering the differences in registrative trial designs and characteristics of enrolled populations, several meta-analyses and real-life studies have tried to trace the safety and efficacy profiles on DOACs, but at present no definitive conclusions can be drawn due to numerous existing biases. One possible aid to help clinicians in their treatment choice is the evaluation of self-reported adverse drug reactions (ADRs) available in drug regulatory agency databases such as the Italian Medicines Agency (AIFA) pharmacovigilance database. We conducted a search in the National Pharmacovigilance Network database, available on AIFA website, in order to retrieve all the ADRs related to oral anticoagulants occurred in the period 2016-2017. We then calculated an ADR risk index (RI) for each drug, where an RI =1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the rate of market share (more safe DOAC). The results showed that rivaroxaban is the DOAC with the lowest RI among the four molecules available today in Italy. Despite the limitations of this study, we believe that ADR RI can be a valuable adjunctive tool to help clinicians in their everyday clinical practice.

Abstract P376: The Monitoring by a Pharmacist Facilitator, of Side Effect, is Useful to Report Adverse Reactions Associated With Antihypertensive Agents in Practical Clinic in South Italy

Adverse Drug Reactions (ADRs) are a serious health related problem, which can limit the treatment options, compliance and even leads to discontinuation of therapy. Unfortunately not in all countries, the reporting reaches standard levels set by the WHO. As well, in our region (Calabria), located in south of Italy, only few reports are usually reported. For these reasons, the Italian Agency of the Drugs (AIFA) has been promoting and financing regional projects with multidisciplinary groups to increase spontaneous reporting. From first January 2018, we started a survey program finalized to report all adverse events from antihypertensive drugs observed in our Cardiovascular Prevention Clinic. We evaluated all of the 250 outpatients (≥18 years), consecutively visited in our clinic, from 1 January 2018 to 30 April 2018. All of these were in antihypertensive treatment (monotherapy or multiple drugs therapy). A total of 20 ADRs were observed. Of the 20 ADRs, 19 were non-serious events; a serious event required hospitalization (atrial-ventricular complete block). Causality assessment has been estimated with the Naranjo algorithm; the results indicated n=19 possible ADRs and n=1 probable. Incidence of ADRs was found to be higher in the age group between 45 and 54 years old (6 of 20) and males experienced more ADRs than females (35%, 7 of 20). ADRs were more frequently associated with combination therapy (65%, 13 of 20) versus monotherapy. Calcium channel-blockers were found to be the most frequently associated drugs with ADRs (n=8), followed by angiotensin receptor blockers (n=4). We compared our reports with the reports, of the same period, available for our region obtained from National Pharmacovigilance Network. During this period were reported 27 side effect reactions in all our region (5 reports in the 2017). In conclusion, in the last 4 months, regional projects, with the creation of a multidisciplinary group composed of Medical and Pharmacists Facilitator, was useful in improving and increase quality and quantity of spontaneous reports in Calabria.

Safety of Antiplatelet Agents: Analysis of 'Real-World' Data from the Italian National Pharmacovigilance Network.

IntroductionAccording to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs).MethodsSuspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class.ResultsClopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the highest reporting trend and ticlopidine the lowest. Most ADRs occurred in the elderly, in particular for ticlopidine. Bleeding represents one of the most reported events (ticlopidine 40%, clopidogrel 26%, prasugrel 42%, ticagrelor 30%) and aspirin was the most frequently associated suspected drug. The majority of ADRs had complete recovery and were non-serious, except for ticlopidine (serious ADRs 53%). Prasugrel showed the highest percentage of ‘life-threatening’ events and ‘death’.ConclusionsBased on the analysis conducted on spontaneous ADRs reporting system in Italy, the safety profile of antiplatelet drugs seems favourable. However, the overall risk-benefit ratio of these drugs needs to be reassessed taking into account the appropriateness of use in particular populations at risk, such as the elderly. Based on this information, we believe that more attention from clinicians and/or an implementation of regulatory measures could be useful for clinical practice.

ADVERSE EVENT (AE) REPORTING FROM MALARIA MASS DRUG ADMINISTRATION (MDA) ROUNDS CONDUCTED IN SOUTHERN ZAMBIA

BackgroundThe National Malaria Control Centre (NMCC) of the Ministry of Health in Zambia is conducting a large-scale mass drug administration (MDA) community randomised-controlled trial to evaluate the effectiveness of different...

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A National Analysis of Data from 10-Year Post-marketing Surveillance.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe and potentially fatal cutaneous adverse drug reaction (the mortality rate is up to 10 %) associated with numerous and apparently heterogeneous drugs. The aetiology is unknown. To report Italian cases of DRESS over a 10-year period. We searched the National Pharmacovigilance Network (NPN) for the term 'drug reaction with eosinophilia and systemic symptoms' from 1 January 2004 to 1 January 2014, to identify all reports of DRESS. Each case was checked to avoid duplication. In the NPN, we identified 91 serious cases of DRESS: 68 were spontaneous, still-unpublished reports, while 23 additional cases were derived from screening of the scientific literature, performed by marketing authorization holders. Notably, the single common element linking all cases of DRESS was intake of a drug containing an aromatic ring. Thanks to the largest national DRESS case series ever reported, we were able to hypothesize, for the first time, that there is an association between use of drugs containing an aromatic ring in their chemical structure and DRESS. This might aid understanding of the aetiology of DRESS and facilitate diagnosis.

OHP-043 The pharmacist “monitor” at the E. R.: the experience of “Gaetano Rummo” hospital of Benevento

BackgroundThe Emergency Room (ER) represents a strategic location for pharmacovigilance due to easy access, permanent availability and a multidisciplinary clinical approach.PurposeTo investigate over a period of twenty-four months how much...