Regional Pharmacovigilance Center Research Articles

Immediate allergies to chlorhexidine: A series of pediatric cases from the French pharmacovigilance database: Immediate allergies to chlorhexidine: series of pediatric cases from the French pharmacovigilance database

BackgroundImmediate allergic reactions to chlorhexidine have been clearly identified in numerous countries, generating governmental warnings worldwide. ObjectivesThe aim of our study was to characterize (i) these allergies, which are less reported in pediatric populations, and (ii) the patient-at-risk profile so as to suggest preventive measures. MethodsIn association with the allergy department and the regional pharmacovigilance center in Rennes University Hospital, France, a multicenter retrospective, descriptive, and observational study was conducted using data from the national pharmacovigilance database for the period of January 1, 2010 to June 30, 2020. Immediate allergies to chlorhexidine cases based on a clinical history compatible with an immunoglobulin E (IgE)-mediated reaction, along with positive allergic testing, were analyzed. ResultsOf the 478 cases identified, 17 pediatric cases of immediate allergic reaction to chlorhexidine (13 cases of grades II–IV anaphylaxis) were retained for the analysis. For 58.8 % of these cases, a history of a previous more moderate reaction to the substance was identified. The reactions occurred most frequently in cases of domestic misuse (88.2 %, n = 15/17) of chlorhexidine to dress a wound. Recurrence was reported for two cases, later leading to severe reactions at each new exposure to the allergen, suggesting an aggravation mechanism. ConclusionThe number of pediatric cases of immediate allergies to chlorhexidine has possibly been underestimated on account of insufficient knowledge of the allergy and in view of its common usage. Information on the method of caring for wounds among children and on the risk of allergic sensitization as well as exploring any unusual reaction to chlorhexidine application could reduce the number of allergic reactions.

Safety profile assessment of HPV4 and HPV9 vaccines through the passive surveillance system of the Veneto Region (Italy) between 2008 and 2022: A 15-year retrospective observational study

In Veneto Region, HPV vaccine has been actively offered to 12 year-old females since 2008, and to 12 year-old males since 2015. The study aims to analyze the safety profile of HPV4v and HPV9v vaccines and perform a case-by-case review of conditions of interest.Spontaneous reports related to HPV uploaded to the database of the Regional Pharmacovigilance Center between 2008–2022 were included. HPV vaccine doses administered until April 2022 in the Veneto Region were considered to calculate the reporting rate (RR).Potential “safety concerns” examined as conditions of interest were included through Standardized MedDRA or preferred terms searching queries. The level of diagnostic certainty was evaluated as per the Brighton Collaboration case definition criteria.A total of 637 reports and 1316 Adverse Events Following Immunizations (AEFI) were retrieved: 469 for HPV4v (73.6 %) and 168 for HPV9v (26.4 %). Serious reports were 71 (11.1 %): 49 (10.4 %) for HPV4v and 22 (13.1 %) for HPV9v. The RR for serious events between 2008–2022 was 6.9/100,000 administered doses, with no differences by vaccine type. Females and adults showed higher overall RR compared to males and to children and adolescents (p < 0.001), this result was confirmed by stratifying analysis by vaccine type. One case of Guillain Barré syndrome, anaphylactic shock, thrombocytopenia, Henoch Schoenlein purpura and four generalized seizures were reviewed.Vaccinovigilance data from the Veneto Region reaffirm a good safety profile for HPV vaccination and found no vaccine-related unexpected events. Such a detailed analysis may assist healthcare providers to advocate properly for HPV vaccination.

Synergizing pharmacometrics and pharmacovigilance for medication error management: the case of secukinumab.

To demonstrate the effective integration of pharmacometrics and pharmacovigilance in managing medication errors, highlighted by a case involving secukinumab in a patient with hidradenitis suppurativa. We present the case of a 41-year-old male with progressive hidradenitis suppurativa, unresponsive to multiple antibiotic regimens and infliximab treatment. Due to a medication error, the patient received 300 mg of secukinumab daily for 4 days instead of weekly, totaling 1200 mg. The regional pharmacovigilance center assessed potential toxicity, and a pharmacometric analysis using a population pharmacokinetic model was performed to inform dosing adjustments. Clinical data indicated that the received doses were within a non-toxic range. No adverse effects were observed. Pharmacometric simulations revealed a risk of underexposure due to the dosing error. Based on these simulations, it was recommended to restart monthly secukinumab injections on day 35 after the initial dose. Measured plasma concentrations before re-administration confirmed the model's accuracy. This case highlights the crucial collaboration between clinical services, pharmacovigilance, and pharmacometrics in managing medication errors. Such interdisciplinary efforts ensure therapeutic efficacy and patient safety by maintaining appropriate drug exposure levels.

Safety of Lipid-Lowering Therapy with Statins according to a Regional Pharmacovigilance Centre

Scientific relevance. Since statins are widely used to prevent cardiovascular diseases, the control of statin-related complications is essential from both medical and social perspectives.Aim. The study aimed to analyse unsolicited reports on adverse drug reactions (ADRs) to control the safety of statin therapy.Materials and methods. The study analysed information on ADRs observed during statin treatment from the reporting forms submitted by medical organisations in Irkutsk to the database of the Regional Centre for Drug Safety Monitoring of the Irkutsk Region in 2011–2022. The causal relationship between ADRs and statin therapy was assessed using the Naranjo scale.Results. The database contained 1068 ADR reporting forms; 12 (1.1%) were spontaneous reports of statin-related complications, including 4 cases (33.4%) of myalgia, 7 cases (58.3%) of myalgia with moderately elevated transaminase levels (3–5 times the upper limit of normal), and 1 case of rhabdomyolysis that required statin discontinuation. In all cases, a reduction in the statin dose resulted in a regression in the clinical symptoms of ADRs. Most ADRs were observed in women with comorbidities (diabetes mellitus, obesity, and hypothyroidism), but the small sample size prevented the authors from testing the identified differences for statistical significance.Conclusions. According to the study results, statins have a reliable safety profile. Adequate and patient-specific selection of statin doses and ADR prevention are important responsibilities of clinical practitioners.

A STUDY TO ASSESS, MONITOR, AND REPORTING OF ADVERSE DRUG REACTIONS IN A TERTIARY CARE TEACHING HOSPITAL: HIMS, HASSAN

Objective: An adverse drug reaction (ADR) is an unwanted, undesirable effect of a medication that occurs during usual clinical use. ADR should be quickly identified and managed to limit their detrimental effects on the patient. This study was undertaken to characterize the pattern of ADRs reported through spontaneous reporting system at ADR reporting unit in a tertiary care teaching hospital. Methods: A prospective, observational study was conducted over 3 years between September, 2017 and August, 2019. The ADRs reported were from patients admitted inpatient department of hospital. Evaluation of patient demographics, drug and ADR characteristics, and outcome of the ADRs. Causality and severity assessment was done by the World Health Organization system and Naranjos scale. Results: 82 cases of ADRs were reported during the study period. More number of ADRs was from General Medicine and Pediatric departments, in which the most affected organ systems were the skin and the gastrointestinal tract. The antibiotic classes mostly accounted were cephalosporins. None of the ADR was fatal. Conclusion: ADRs to antibiotics are common and will be resulted in increased health-care cost due to the need of some interventions and increased length of hospital stay. The health-care system should promote proper documentation and periodic reporting to regional pharmacovigilance centers to ensure drug safety.

General medicine and notification of adverse reactions: contributions of health insurance representatives

In order to reduce the under-reporting of adverse drug reactions (ADR) in general practice, the Caen Normandie regional pharmacovigilance center (CRPV) has implemented a training program for the French health insurance representatives (DAM) of the Manche department in order to raise awareness among general practitioners (GPs) to ADR reporting. During quarterly visits of DAM to GPs, the mode of operation and the value of pharmacovigilance reporting was presented. This pilot study presents the impact of these DAM visits to GPs in term of ADRs reporting quantification. Assessment of this first year showed a doubling of ADR reporting by GPs of the Manche department in 2019 compared to 2017 and 2018. This phenomenon was not found in the two control departments (departments of Calvados and Orne) where the information had not been issued. These ADRs first concerned drugs of the renin-angiotensin system, then psychotropic drugs and anti-infectives. These were cutaneous, then neurological and gastrointestinal ADRs, preferentially affecting women. This experimentation should continue on a larger scale. The longer-term evaluation of this tool also requires evaluating its relevance.

Monitoring the safety of drugs and COVID-19 vaccines by the French Pharmacovigilance Centers during the pandemic: A win-win bet with Health Authorities!

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic virus was a "health crisis" and a significant burden also for the French pharmacovigilance system. It took its toll in 2 phases, the first being in early 2020 when very little was known, and during which the missions of the 31 Regional Pharmacovigilance Centers (RPVCs) from university hospitals were to detect adverse reactions of drugs used in the context of the disease. Whether as a possible aggravating role on COVID-19, or displaying a different safety profile during its course, or to assess safety of curative treatment, this phase preceded that of the arrival of dedicated vaccines. Then the RPVCs' missions were to detect, as early as possible, any new serious adverse effect leading to a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two distinct periods, signal detection remained the core business of the RPVCs. Each RPVC had to organize itself to handle an unprecedented surge of declarations and requests for advice, from health care professionals and patients alike. "Leading" RPVCs, who were in charge of monitoring vaccines, had to deal with an extraordinary workload (still going on to this date), to generate in real-time and on a weekly basis, a summary of all the adverse drug reaction (ADR) reports as well as an extended analysis of the different safety signals. The organization put in place at the beginning of the health crisis, adapted to the context of the vaccines, allowed to meet the challenge of real-time pharmacovigilance monitoring, and to identify many safety signals. Efficient "short-circuits exchanges" with the French Regional Pharmacovigilance Centers Network (RPVCN) were paramount to the National Agency for the Safety of Medicines and Health Products (ANSM) to develop an optimal collaborative partnership. The French RPVCN has shown at this occasion both agility and flexibility, swiftly adapting to vaccine- and media-related unrest, and demonstrated its effectiveness in the early detection of safety signals. This crisis also confirmed the superiority of manual/human signal detection over automated ones, as the most effective and powerful tool to date to rapidly detect and validate a new ADR and enable to elaborate rapid risk reduction measures. To maintain the performance of French RPVCN in signal detection and to monitor all drugs as they should, and as expected by our fellow citizens, a new funding model should be considered.

Pharmacovigilance des médicaments et des vaccins contre la COVID-19 durant la pandémie : comment le Réseau français des centres régionaux de pharmacovigilance a relevé le défi ?

The pandemic subsequent to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus resulted, for the French institutional pharmacovigilance, in a "health crisis" in 2 phases: the coronavirus disease 2019-"COVID-19" phase during which the missions of the Regional Pharmacovigilance Centres (RPVC) were to detect a possible impact of drugs on this disease, as whether existed a possible aggravating role of certain drugs, or the safety profile of drugs used for the management of COVID-19 could evolve. The second phase followed the availability of COVID-19 vaccines, during which the RPVCs' missions were to detect as early as possible any new serious adverse effect, source of a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two periods, signal detection remained the core business of the RPVCs. The RPVCs had to organize themselves to handle an historical surge of declarations and requests for advice, whereas the RPVCs in charge of monitoring vaccines had to deal with an extraordinary dense activity over a long period of time, in order to produce in real time and on a weekly basis, a summary of all the declarations and an analysis of safety signals. The national organization put in place made it possible to meet the challenge of real-time pharmacovigilance monitoring of 4 vaccines with conditional marketing authorizations. Short-circuit efficient exchanges with the French Regional Pharmacovigilance Centres Network was paramount for the French National Agency for medicines and health products (Agence nationale de sécurité du médicament et des produits de santé) to develop an optimal collaborative partnership. The RPVC network has shown agility and flexibility, has been able to adapt swiftly and demonstrated its effectiveness in the early detection of safety signals. This crisis confirmed the superiority of manual/human signal detection as the most effective and powerful tool to date, to rapidly detect a new adverse drug reaction and enable to elaborate rapid measures of risk reduction. In order to maintain the performance of French RPVCs in signal detection and to monitor all drugs as they should and as expected by our fellow citizens, a new funding model correcting the inadequacy of RPVCs' expertise resources in relation to the volume of reports should be considered.

French pharmacovigilance survey of casirivimab - imdevimab monoclonal antibodies in coronavirus disease (COVID-19)

Casirivimab and imdevimab (Ronapreve®) are two recombinant human monoclonal antibodies (mAbs) that bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, preventing the virus from entering cells. In March 2021, this drug was granted emergency use authorisation (EUA) in France for early treatment of COVID-19 in patients at increased risk of progression to severe COVID-19. In August/September 2021, the indication was expanded to COVID-19 prevention (pre- or post-exposure prophylaxis) and treatment of hospitalised patients requiring non-invasive oxygen therapy. The aim of the study was to better describe the adverse drug reaction (ADR) profile and detect safety signals of this new drug used in COVID-19 treatment. We described ADR profile with casirivimab/imdevimab reported as suspect/interacting drug to the French pharmacovigilance network and the pharmaceutical company between 17/03/2021 and 30/06/2022. Data presented correspond to the 2 periods of the pharmacovigilance survey: the first carried out by the pharmaceutical company for curative and prophylactic uses and the second by Toulouse university regional pharmacovigilance center (RPVC). A total of 384 reports were analysed and 256 were "serious". ADR profile was comparable between the 2 periods and between curative and prophylactic use, corresponding to expected ADRs such as infusion-related reactions and hypersensitivity, inefficiencies or worsened infections and deaths. Two potential pharmacovigilance signals were also studied: acute pulmonary oedemas and sudden deaths. No pharmacovigilance signal emerged from this 15 months French pharmacovigilance survey. Moreover data from published studies are also reassuring. This pharmacovigilance survey was the first one for the new version of EUA and with a new ADR reporting process i.e. declaration to the RPVC instead of the pharmaceutical company. Casirivimab/imdevimab is no longer used in France today but we continue to monitor this drug for any future evidence of resurgent activity on a new variant of Sars-CoV-2.

Peripheral facial palsy post SARS-CoV-2 vaccine: A regional pharmacovigilance cases series

Peripheral facial palsy (PFP) is a rare adverse reaction identified from clinical trials of coronavirus disease 2019 (COVID-19) vaccines (messenger ribonucleic acid [mRNA] and viral vector). Few data are available on their onset patterns and risk of recurrence after re-injection of a COVID-19 vaccine; the objective of this study was to describe PFP cases attributed to COVID-19 vaccines. All cases of facial paralysis reported to the Regional Pharmacovigilance Center of Centre-Val de Loire area between January and October 2021, in which the role of a COVID-19 vaccine was suspected, were selected. Based on initial data and following additional information requested, each case was reviewed and analyzed to include only confirmed cases of PFP for which the role of the vaccine could be retained. From the 38 cases reported, 23 were included (15 excluded because of diagnosis not retained). They occurred in 12 men and 11 women (median age of 51 years). The first clinical manifestations occurred with a median time of 9 days after COVID-19 vaccine injection, and the paralysis was homolateral to the vaccinated arm in 70%. The etiological workup, always negative, included brain imaging (48%), infectious serologies (74%) and Covid-19 PCR (52%). Corticosteroid therapy was prescribed for 20 (87%) patients, combined with aciclovir in 12(52%). At 4-month follow-up, clinical manifestations had regressed completely or partially in 20 (87%) of the 23 patients (median time of 30days). From them 12 (60%) received another dose of COVID-19 vaccine and none had a recurrence and the PFP regressed despite the second dose in 2 of the 3 patients not fully recovered at 4 months. The potential mechanism of PFP after COVID-19 vaccine, which don't have a specific profile, is probably the interferon-γ. Moreover, the risk of recurrence after a new injection appears to be very low, which makes it possible to continue the vaccination.

COVID-19 et vaccins à adénovirus : expérience française de suivi renforcé de pharmacovigilance

As part of the COVID-19 vaccination campaign, the National Agency for the Safety of Medicines and Health Products and all 31 regional pharmacovigilance centers were mobilized in an exceptional reinforced vaccine pharmacovigilance surveillance system. Concerning adenovirus vaccines, Vaxzévria® and Jcovden®, this national system, based on the daily analysis of notified cases of adverse events, has allowed the early identification of safety signals, some of which have been validated, others still under analysis, common to mRNA vaccines or more specific of adenovirus vaccines such as Vaccine Induced Immune Thrombocytopenia. Complementing european and international actions, this follow-up has contributed to a better definition of the safety profile of these vaccines and has led to redefine the vaccine strategy in our country. Although today these two vaccines have no longer place in the national vaccine strategy, they are still used in other countries, where the experience acquired could be useful and will contribute to fuel the reflection on future therapies involving viral vectors.

Healthcare professionals’ information need related to antiseizure medication use in breastfeeding patients with epilepsy. Retrospective analysis of enquiries to Norwegian medicines information and pharmacovigilance centers

BackgroundSafety information of antiseizure medication (ASM) during breastfeeding is scarce and conflicting. We aimed to identify characteristic traits of safety concerns among healthcare professionals by reviewing enquiries to the Norwegian Regional Medicines Information and Pharmacovigilance Centres (RELIS). MethodEnquiries related to breastfeeding, epilepsy, and ASM identified by their ATC-numbers were retrieved from the RELIS database of question-and-answer pairs (QAPs) by combining indexed and Boolean database searches and manual inspection. 112 QAPs were analyzed retrospectively using descriptive statistics. ResultsHospital-employed physicians and nurses were puzzled by ambiguous or conflicting drug information advice and called for general information about the compatibility of an ASM with breastfeeding, mainly related to lamotrigine and levetiracetam. Other enquiries were related to co-medication with other drugs, mainly antidepressants. Half of the enquiries were posed after birth, 12 of these motivated by suspected adverse events in the infants. ConclusionHealthcare professionals with acknowledged high competence in the topic were uncertain about the prevailing safety information of ASM during breastfeeding. The fear to harm the infant may lead to the decision not to recommend breastfeeding. Future information strategies should aim to reach these professions, and support their information need on this topic.

What place for intelligent automation and artificial intelligence to preserve and strengthen vigilance expertise in the face of increasing declarations?

In 2018, the "Ateliers de Giens" (Giens Workshops) devoted a workshop to artificial intelligence (AI) and led its experts to confirm the potential contribution and theoretical benefit of AI in clinical research, pharmacovigilance, and in improving the efficiency of care. The 2022 workshop is a continuation of this reflection on AI and intelligent automation (IA) by focusing on its contribution to pharmacovigilance and the applications and tasks could be optimized to preserve and strengthen medical and pharmacological expertise in pharmacovigilance. The evolution of pharmacovigilance work is characterized by many tasks with low added value, a growing volume of pharmacovigilance reporting of suspected side effects, and a scarcity of medical staff with expertise in clinical pharmacology and pharmacovigilance and human resources to support this growing need. Together, these parameters contribute to an embolization of the pharmacovigilance system at risk of missing its primary mission: to identify and characterize a risk or even a health alert on a drug. The participants of the workshop (representatives of the Regional Pharmacovigilance Centres (CRPV), the French National Agency for Safety of Medicinal Products (ANSM), patients, the pharmaceutical industry, or start-ups working in the development of AI in the field of medicine) shared their experiences, their pilot projects and their expectations on the expected potential, theoretical or proven, AI and IA. This work has made it possible to identify the needs and challenges that AI or IA represent, in the current or future modes of organization of pharmacovigilance activities. This approach led to the development of a SWOT matrix (strengths, weaknesses, opportunities, threats), a basis for reflection to identify critical points and consider four main recommendations: (1) preserve and develop business expertise in pharmacovigilance (including research and development in methods) with the integration of new technologies; (2) improve the quality of pharmacovigilance reports; (3) adapt technical and regulatory means; (4) implement a development strategy for AI and IA tools at the service of expertise.

Did the COVID-19 Pandemic Affect Contrast Media-Induced Adverse Drug Reaction’s Reporting? A Pharmacovigilance Study in Southern Italy

Medical imaging is required for a complete clinical evaluation to identify lung involvement or pulmonary embolism during SARS-CoV-2 infection or pulmonary and cardiovascular sequelae. Contrast media (CM) have undoubtedly been useful in clinical practice due to their ability to improve medical imaging in COVID-19 patients. Considering their important use, especially in hospitalized COVID-19 patients, and that increased use of a medical tool could also be associated with its deeper knowledge, we chose to explore if new information emerged regarding CM safety profiles. We analyzed all Individual Case Safety Reports (ICSRs) validated by Campania Pharmacovigilance Regional Centre from 1 January 2018 to 31 December 2021 and reported a CM (ATC code V08) as a suspected drug. We compared CM-related reporting between 2 years before (period 1) and 2 years during (period 2) the COVID-19 pandemic. From our analysis, it emerged that, during the COVID-19 pandemic, CM-related ADR reporting decreased, but a significant increase in reporting of serious cases emerged. Serious ADRs were mainly related to iodinated CM (V08A ATC) compared to magnetic resonance imaging CM (V08C ATC). Cutaneous and respiratory disorders were the most frequently reported in both periods. No new or unknown ADRs were reported in the overall study period.

P-308 Spontaneous reports of menstrual cycle disorders after mRNA Covid-19 vaccine

Study questionDoes the mRNA Covid-19 vaccine have an influence on the ovulatory process and menstrual disorders?Summary answerMenstrual disorders were more frequently reported in women aged 25 to 45 years, mainly amenorrhea and increased cycle length, and were often not severe.What is known alreadyMenstrual disorders can be due to several factors, including stress, especially during a pandemic or sometimes during a vaccination. However, the SARS-CoV-2 spike protein is able to interact with the human ACE2 receptor, which is widely expressed in the ovaries, uterus, vagina, and hypothalamic pituitary axis. Accumulating evidence now suggests that 2019-nCoV/ACE2 may interfere with the female reproductive functions, leading to menstrual disorder. The role of this spike protein is also to trigger an immune response, used in particular for mRNA vaccines. The aim of this study is to describe the side effects on menstrual cycles after mRNA Covid-19 vaccine.Study design, size, durationThis is a descriptive analysis of adverse events affecting the menstrual cycle reported to a regional pharmacovigilance center between May 2021 and January 2022. A case-by-case review was performed to collect variables characterizing the patient and the reactions.Participants/materials, setting, methodsPatients upper 11 years and under 60 years with mRNA Covid-19 vaccine suspected, were enrolled. Medical Dictionary for Drug Regulatory Activities (MedDRA) was used to identify cases of menstrual disorders. Reactions related to the following System Organ Classes from MedDRA were extracted: amenorrhea, disorder of menstrual cycle, dysmenorrhea, long menstrual cycle, menorrhea, menometrorrhagia, metrorrhagia. Seriousness was defined, according to the WHO, as the occurrence of death, lifethreatening, hospitalisation, requirement of consultation.Main results and the role of chanceSide effects with mRNA Covid-19 vaccine concerned women in 67.8% (N = 1306) of cases, between 12 and 59 years old.5.1% (N = 67) were related to the menstrual cycle. Serious cases 53.7% (N = 36) were no more frequent than in the whole women 50.1% (N = 654). Menstrual disorders were more represented in the 25-45 age group 64.2% (N = 43) vs 12-24 age group 14.9% (N = 10) and over 45 age group 20.9% (N = 14) p = 0.001. Menstrual disorders not recovered at the time of reporting accounted for 38.9% (N = 26). For the all studied population, amenorrhea or increased cycle length were more frequent 53.8% (n = 36) vs increased duration of menstruation or menorrhagia 26.8 % (N = 18) or increased frequency of menstruation metrorrhagia/menometrorrhagia 22.4% (N = 13) p < 0.001. Long cycles or amenorrhea were most represented in the 12-24 age group 90% (N = 9) p < 0.0001 and 25-45 age group 62.7% (N = 27) p < 0.1 vs dysmenorrhea , menorrhea, metrorrhagia, menometrorrhagia. The difference was not significative in women over 45 years old 35.7% (N = 5). Finally amenorrhea and long cycles were less often reported with severity 22.2% (N = 8) than other menstrual side effect (dysmenorrhea , menorrhea, menometrorrhagia, metrorrhagia) 45.2% (N = 14), p < 0.1.Limitations, reasons for cautionThe most important limitation relies on the spontaneous reporting. Underreporting is estimated to about 90%. It was probably not the case for side effect due to the Covid-19 vaccination. Furthermore, serious cases are more likely to be reported than mild or minor cases resulting in a possible reporting bias.Wider implications of the findingsThe cases reported reflect the experience of clinicians who were asked about cycle disturbances after covid-19 vaccination (V. Male BMJ 2021).We observed more frequent changes in cycle length but not in menstrual length, as reported by A. Edelman (Obstet Gynecol 2022). Fertility may be punctually affected by Covid-19 vaccination.Trial registration numberAnalyzing anonymous data, being retrospective and non-interventional, the approval of an Ethics committee was not necessary according to the Good Clinical Practice in pharmacovigilance.

Delayed eczematous skin reaction as an adverse drug reaction to immunoglobulin infusions: A case series

BackgroundPompholyx and eczematous reactions are known adverse reactions to intravenous immunoglobulins (IVIg) infusion, but little is known about their clinical characteristics, associated outcomes and management. ObjectiveTo describe IVIg-induced eczematous skin reactions. MethodsWe conducted a retrospective study on cases of delayed skin reactions post-IVIg infusion notified to the French Regional Pharmacovigilance Centre from 1985 to 2020. ResultsA total of 27 patients were identified, of whom 85% were male. IVIg infusions were given in a neurological indication in 82% of cases. Eczematous skin reactions occurred in two-thirds of cases after the first infusion, with a median time to onset of 11 days. Palmoplantar pompholyx was the most common presentation, being seen in 63% of patients. Other eruptions were erythemato-squamous or maculopapular. Eight patients were classified as severely affected and developed extensive lesions (>50% BSA). One third of the 27 patients required hospitalization. All of the severe eczematous reactions involved males receiving high doses of IVIg for neurological diseases. Biopsies of severe cases revealed a common non-specific eczematous pattern. Relapses were frequent and more severe than the initial reaction. Reintroduction of the same IVIg product consistently resulted in relapse, whereas switching IVIg type produced relapse in only 53% of patients. ConclusionWe present the largest retrospective study of delayed skin reactions after IVIg infusions. This side-effect may be severe and have a polymorphic presentation. Relapse occurs frequently but less consistently after IVIg switch.

Myocarditis, pericarditis, and COVID-19 mRNA-vaccination.

[no abstract, showing first paragraph]Dear Editor, We would like to share ideas on “Myocarditis and pericarditis in association with COVID-19 mRNA-vaccination: cases from a regional pharmacovigilance centre” [1]. Istampoulouoglou et al. concluded that “In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible …..[1].” We agree that COVID-19 vaccination might cause adverse effects, and myocarditis is an important one. However, it is difficult to clearly state that the vaccine cause the problem. The pathogenesis of vaccine-related myocarditis is still unclear. It might be an immunopathology. In that case, an abnormal immune parameter will be an important clue. However, it usually lacks for data and it cannot rule out pre-vaccination occult abnormal immunity.

Assessment of the Current State of Pharmacovigilance System in Pakistan Using Indicator-Based Assessment Tool.

Objectives: Pakistan felt the need for an effective and robust pharmacovigilance (PV) system after one of the deadliest drug-related tragedies causing more than 300 deaths in 2012. The country set up its national PV center in 2015 and joined WHO’s Program for International Drug Monitoring (PIDM) in 2018 as a full member. The current study was aimed to evaluate the PV system’s functionality, identify the gaps, areas of improvement, and a strategy to lead a functional PV system in Pakistan. Methods: The descriptive cross-sectional study was conducted by providing an interviewer-administered questionnaire of the PV system across Pakistan by utilizing the Indicator based Pharmacovigilance assessment tool (IPAT). By a convenience sampling method 36 study participants were selected from the Drug Regulatory Authority of Pakistan (DRAP), drug administration of provincial health departments of 4 provinces and federally affiliated areas, 5 national public health programs, and 23 public and private hospitals. The assessment includes document review, interviews of the key informants by structured open-ended questions, and a review of websites of relevant organizations. Results: Drug Regulatory Authority of Pakistan (DRAP) with a national PV center received a 75% overall performance score on IPAT. To be regarded as “minimally functioning,” a country’s PV and drug safety system must meet all core indicators. DRAP scored 80.76% on the core indicators so cannot be deemed functional at this time. The only province with a regional PV center, Punjab, had scored 72.13% on relevant parameters. Despite receiving funding from the Global Fund, none of the National Public Health Programs (PHPs) have PV centers or associated activities. All hospitals except two private hospitals could not qualify the minimum requirements for functional PV. The absence of a legal framework for mandatory ADR reporting, lack of drug information center, budgetary constraints, no active surveillance activities, the nonexistence of pharmacovigilance risk assessment expert committee, and insufficient coordination among stakeholders were identified as major gaps. Conclusion: The results of the study reveal that Pakistan’s PV system is not fully functional at all levels. A two-phased strategy encompassing the non-financial and financial interventions is proposed to improve the PV systems at the national, provincial, PHPs, and hospitals levels.

Scope of Pharmacovigilance for Ayurvedic Drugs in Nepal: A Review

Ayurveda along with complementary and alternative medicine (CAM) systems have their own principles, have their own pharmacopeia, but are practiced as over the counter drugs without an authentic prescription. Government of Nepal nominated Department of Drug Administration (DDA) in October 2004 as the focal point (National Pharmacovigilance Centre) to liaison with WHO collaborating centre for International Drug Monitoring (IDM), Sweden and started collecting adverse drug reactions (Nepal became a WHO program member in July 2006). Nepal joined the international pharmacovigilance program as a full member in 2007. This study is to reflect the present status of pharmacovigilance in Nepal and put light on scope of pharmacovigilance on drugs of Ayurveda and other complementary alternative systems in Nepal. For which review and analysis of concerned published literatures in print form and in online database. At present; 12 regional pharmacovigilance centers are there in Nepal. Currently, the clear pattern and scope of adverse drug reactions (ADRs) in Nepal remains unexplored. For Ayurveda drugs the concept of pharmacovigilance is not yet formally introduced in Nepal. No policy has been formulated for the same. The conventional belief that Ayurveda drugs have no ADRs should be transformed.

Comparative study of the adverse event profile of hydroxychloroquine before and during the Sars-CoV2 pandemic

AimsAt the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were no clinically-tested medications for the effective treatment of coronavirus disease. In this context, on 5 March 2020, the French Public Health Council issued several recommendations for the therapeutic management of this new disease, including the use of hydroxychloroquine (HCQ). An unexpected cardiovascular safety signal was quickly identified as being more frequent than expected thanks to the reports of adverse drug reactions (ADRs) submitted to French regional pharmacovigilance centres (RPVC). The objective of this study was to compare all ADRs reported with HCQ used in its usual indication, collected before the pandemic period (1985 to 31 December, 2019) with those reported with the coronavirus disease 2019 (COVID-19) indication (1 January to 21 July, 2020).MethodsFor this purpose, reports were extracted from the French pharmacovigilance database and analysed for these two periods.ResultsOur study showed a different safety profile in COVID-19 patients with more cardiac disorders (57% of ADRs versus 5% before the pandemic period), especially QT interval prolongation, resulting from an interaction with azithromycin in more than 20% of cases. Hepatobiliary disorders were also significantly more frequent.ConclusionsThese observations could be associated with the effect of the virus itself on the various organs, the profile of the patients treated, and concomitant drug treatments.