Pharmacovigilance Data as a Trigger to Identify Antimicrobial Resistance and Inappropriate Use of Antibiotics: A Study Using Reports from The Netherlands Pharmacovigilance Centre

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and pharmacovigilance has the potential to strengthen current antimicrobial stewardship strategies. This study aimed to characterize AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre; (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs); (3) Results: Between 1998 and January 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n = 89; 35%), colistin (n = 30; 11.9%), cipro-floxacin (n = 16; 6.3%), doxycycline (n = 14; 5.5%), and aztreonam (n = 12; 4.8%). The PTs used included off label use (n = 91; 36.1%), drug ineffective (n = 71; 28.2%), product use in unapproved indication (n = 28; 11.1%), pathogen resistance (n = 14; 5.6%), and drug resistance (n = 13; 5.2%). 54% of the reports were on Watch antibiotics and 19% were involved in the Reserve group. In the Watch group, “off label use” and “product use in unapproved indication” were the most frequent PTs and the majority of reports on Reserve antibiotics were coded as “Off label”. A sharp increase in the number of reports was observed in the three consecutive years with 21 in 2013, 54 in 2014, and 83 in 2015; (4) Conclusions: In addition to existing AMR monitoring strategies, pharmacovigilance databases can serve as a source of data on suspected resistance and inappropriate use. Future research should explore how these AMR-relevant MedDRA Terms are used in resource-limited settings with less capacity to generate laboratory-confirmed resistance data.

Pharmacovigilance in Pakistan: A Peek into the Future Prospects

The dire need for drug monitoring and surveillance principles are practices governing the safety profiles of the medicines arose following the 1960’s Thalidomide disaster that resulted in phocomelia in thousands of new born babies [1]. Since then Pharmacovigilance centers have been established in the member countries, which report all the untoward drug reactions to Uppsala Monitoring Centre (UMC) that is designated to perform further investigations and global dissemination of the necessary information [2]. Currently 134 countries that are collaborating with UMC of which 96% are developed while 27% are developing countries which are lagging behind as per the unavailability of infrastructure and resources [3]. Pakistan National Pharmacovigilance Centre (PNPC) Ministry of health initiated pharmacovigilance activities in Pakistan in 1994; however a stable system could not be established owing to the unavailability of human resources as well as the infrastructure [4]. Later the suggestion for the establishment of Pakistan National Pharmacovigilance center (PNPC) was mentioned by the national drug policy in 2003 [5], however, the launch of the centre took place in 2012 following the tragic death of around 200 cardiac patients in Lahore as a result of an accidental mixing of Isosorbide mononitrate with Pyrimethamine that resulted in severe deficiency of folic acid, destroying the platelets and causing profuse internal bleeding [6,7]. In the view of the gravity of the situation, an independent authority for drug regulation (Drug regulatory authority of Pakistan – DRAP) was founded under the orders of the Pakistan Supreme Court in 2018. This authority was established for ensuring availability and safety of the medications. In order to devise an infrastructure for the post-marketing drug surveillance, DRAP in collaboration with the Pharmacopoeia of US established PNPC in the year 2017 and by 2018 Pakistan was included as a member in the UMC [8]. The centre has laid down protocols and practices for the international and national coordination and has added Pakistan 134th on the drug monitoring WHO program. Currently the PNPC is being governed by the 2012 Act of DRAP for developing, promoting and regulating the pharmacovigilance system in the country and coordination with provincial sectors to empower the hospitals to establish their own pharmacovigilance centers [9]. Future Perspectives of PNPC PNPC has come a long way still being in infancy and is setting up future goals towards development. Proper guidelines have been formed and an organized system was established by PNPC till 2018 for reporting Adverse Drug Reactions (ADRs) online. Training workshops for the members are regularly carried out to keep the work force ready and updated about the regulatory and management aspects. A regional centre of PNPC was announced to be established in Islamabad in November, 2019 [10]. PNPC has also upgraded its recording, monitoring and reporting system for ADRs via affiliation with the VigiFlow database of the country permitting maximum control locally effectively managing and analyzing the country-wide data [11]. The provincial, market authority and public health stakeholders are called for regular meetings. PNPC has composed comprehensive guidelines and legislation regarding pharmacovigilance protocols that are meant to provide legal surveillance of the activities. In the long run, the PNPC is planning for the establishment of provincial pharmacovigilance centers in each province, and the sub-regional centers and integrating them into the national database. Good practices of pharmacovigilance will utilize the obtained data to bring about safety protocols. However, a number of hurdles are still in the way. There are constraints related to logistics and legal matters as well as finances. There is a requirement of a collaborated effort by all the stake holders in the country. Healthcare professionals have a limited awareness about PNPC protocols and a reluctance to report the adverse events. The main issue is getting the healthcare workers and public normalized and used to with the reporting and surveillance system in order to cope up with the reluctance to report and awareness about the protocols. The success of this system is actually two way and it depends on the response from the reporting stake holders as much as it does on the system of the organization itself. The public health programs, hospitals and healthcare units need to be encouraged to participate in the PNPC system for proper reporting and detection of serious ADRs. Training and awareness sessions need to be conducted to form and normalize a reporting culture among heath care workers in Pakistan. Methods for assessment of severity, detection of cause and preventability of the reported ADRs, need further standardization. Furthermore, the international collaboration is still deficient as the WHO data bank does not have any adverse effect reported data from Pakistan; therefore, the gap needs to be filled as a priority. Although a lot still needs to be don e, a clear progress has been noted in the past couple of years. With the introduction of new guidelines and strategies; route to further progress is clearly marked but the effort has to involve all the stake holders which will start by the realization and understanding of the significance and need for a properly functional pharmacovigilance system in the country.

ASSESSMENT OF COMMUNITY PHARMACIST AWARENESS ON ADVERSE DRUG REACTION (ADR) AND PHARMACOVIGILANCE REPORTING SYSTEM IN KHARTOUM LOCALITY, SUDAN

Introduction: Adverse drug reactions resulting from the use of a medicinal product and were harmful or unpleasant reaction. Pharmacovigilance is related pharmaceuticals product after marketing and associated with collection, detection, assessment, monitoring and prevention of adverse effects. The aim of study is to recognize the awareness of pharmacists regarding pharmacovigilance and adverse drug reactions reporting. Methodology: Descriptive cross-sectional study conducted to 237 pharmacists working in Khartoum’s locality pharmacies from August 2019 to March 2020 selected by simple randomization. The data were collected by face to face interview using self-administrated Questionnaire and analyzed by SPSS version 23. Results: 57.4% from the total sample size never seen adverse drug reactions reporting form, 76.4% never receive training on how to report it and only 10.5% from the pharmacists in the study report it to pharmacovigilance center. 79% from pharmacists in the study were not aware about existence of pharmacovigilance program in Sudan. 51.5 % from pharmacists have good attitude about adverse drug reactions and pharmacovigilance in Sudan while 48.5% had poor attitude. Difficulty in communicating with pharmacovigilance centre in Sudan and how to write the report were the factors discourage pharmacists from reporting of adverse drug reactions. Conclusion: Community pharmacists have insufficient knowledge about the concept of pharmacovigilance and spontaneous ADRs reporting while they had positive attitudes toward pharmacovigilance, despite their little experience with ADRs reporting, this can be strengthened by educational trainings and workshops. Peer Review History: Received: 4 September 2021; Revised: 9 October; Accepted: 29 October, Available online: 15 November 2021 Academic Editor: Dr. Jennifer Audu-Peter, University of Jos, Nigeria, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Neelam H. Zaidi, Fiji National University, Fiji, [email protected] Dr. U. S. Mahadeva Rao, Universiti Sultan Zainal Abidin, Terengganu Malaysia, [email protected] Dr. Hayriye Eda Şatana Kara, Gazi University, Turkey, [email protected] Dr. Andrzej Szymański, Poznan University of Technology, Poland, [email protected] Similar Articles: AWARENESS OF PHARMACISTS TOWARDS ASPARTAME SIDE EFFECTS IN KHARTOUM CITY, SUDAN ASSESSMENT OF THE ROLE OF COMMUNITY PHARMACISTS IN MANAGEMENT OF HIV-POSITIVE INDIVIDUALS IN THE SOUTHERN REGION OF NIGERIA

A Study on Adverse Drug Reactions in a Tertiary Care Hospital of South India

Medication-related adverse events or adverse drug reactions (ADRs) are harmful events caused by medication. ADRs could have profound effects on the patients’ quality of life, as well as creating an increased burden on the healthcare system. ADRs are one of the rising causes of morbidity and mortality internationally, and will continue to be a significant public health issue with the increased complexity in medication, to treat various diseases in an aging society. This was a prospective and observational study conducted in medicine department of sagar hospital, Bengaluru. Patients were enrolled based on the criteria with a suitable statistical tool. Among 64 patients, 33 (51.6%) female and 33 (48.44%) were males found. ADRs were more in the age group of 41 – 60, 32 (50%), less in the age group is 0 – 20, 04 (6.25%). Significantly higher numbers of ADRs caused by the antibiotics 25 (39%) followed by antihyperlipidicmic and anti-arrythmic 01 (1.56%), Most of the ADRs were moderate 40 (62.5%) and sever 01 (1.56%) in nature. Most commonly affected organ is dermatological system 32 (50%). Majority of the ADRs were associated with antibiotics. Commonly skin related ADRs was found in this study. The results provided an insight to the Health care Providers on the importance of monitoring and reporting of ADRs. Our study results emphasize a need for establishing a pharmacovigilance centre to ensure the safe use of drugs.

Myocarditis and pericarditis in association with COVID-19 mRNA-vaccination: cases from a regional pharmacovigilance centre

In this article we summarize suspected adverse events following immunization (AEFI) of pericarditis, myocarditis and perimyocarditis that were reported by our regional pharmacovigilance centre after COVID-19 mRNA-vaccination and discuss their association with these vaccines. Seventeen cases were reported between March and July 2021. Of these, nine had perimyocarditis, five myocarditis and three pericarditis. Twelve patients were male (71 %). The median age was 38 years (range 17 - 88). The most commonly observed presenting symptom was acute chest pain (65%). While 47% of the patients were previously healthy, 53% had at least one pre-existing comorbidity, with hypertension being the most prevalent (24%). The European Society of Cardiology diagnostic criteria for the reported AEFIs were fulfilled in twelve cases (71%). The AEFIs occurred after the first vaccine dose in six cases (35%), after the second vaccine dose in ten cases (59%) and after both doses in one case (6%). The median latency of all AEFIs taken together was 14 days (range 1 - 28) after the first vaccination and 3 days (range 1 - 17) after the second one. All patients except one were hospitalized (94%) with a median length of stay of 7.5 days (range 3 - 13). The majority of patients (n = 11, 65%) did not experience any complications, and 13 (77%) of the patients were recovered or recovering at the time of discharge. In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible by the pharmacovigilance centre.

Pharmacovigilance Bibliometrics: Visualizing Thematic Development in the Category of Pharmacology and Pharmacy in Web of Science

Introduction: Pharmacovigilance studies include monitoring and preventing the occurrence of new, rare, or serious adverse drug reactions, making it possible to discover new safety issues without delay. Bibliometrics could assist scholars to analyze the development of pharmacovigilance.Methods: The MeSH terms of both pharmacovigilance and “adverse drug reaction reporting system” were retrieved in the Science Citation Index Expanded. The articles from 1974 to July 2021 in the pharmacology and pharmacy category were recruited. The citation reports including the publication numbers, h-index, and sum and average cited times in terms of annuals, countries, organizations, authors and journals were tabulated. The coauthorship relations in the analysis units of countries, organizations, and authors; the top 10 burst references; the document citation network; and the author’s keywords co-occurrence overlay map were visualized by bibliometric software including the website (https://bibliometric.com/), VOSviewer, CiteSpace, and CitNetExplorer.Results: From 1974 to the present, the most high-yield publication year, country, institute, author, and journal were 2020 (n = 222), France (n = 522), Netherlands Pharmacovigilance Centre Lareb (n = 82), Jean–Louis Montastruc (n = 125), Drug Safety (n = 384), respectively, in all 2,128 articles. Similarly, the United States, Institut National de la Sante et de la Recherche Medicale, and Jean–Louis Montastruc had the most coauthorship strength at the macrolevel (global), mesolevel (local), and microlevel (individual). The topics of burst references covered are the development of methodology, issues of patients reporting and under-reporting, evaluation of methods and databases, assessment of causality, and perspectives in pharmacovigilance. Eight clusters were grouped in the document citation network. “Pharmacovigilance,” “adverse drug reactions,” “pharmacoepidemiology,” “drug safety,” and “signal detection” were the research priorities, while “drug-related side effects and adverse reactions,” “VigiBase,” “disproportionality analysis,” “social media,” “FAERS,” “chemotherapy,” “patient safety,” “reporting odds ratio,” and “preventability” might be the future research hotspots.Conclusion: Positive synergies can be observed in this study by employing the multiple software tools which established the relationship between the units of analysis. The bibliometric analysis can organize the thematic development and guide the hotspots of pharmacovigilance in pharmacology and pharmacy.

Adverse Drug Reaction Reports Containing AMR-Relevant MedDRA Terms in the Dutch Pharmacovigilance Database

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and Pharmacovigilance (PV) has the potential to strengthen current antimicrobial stewardship (AMS) strategies. This study aimed to characterise AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre (Lareb); (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs).; (3) Results: Between 1998 and Jan 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n=89; 35%), colistin (n=30; 11,9%), ciprofloxacin (n=16; 6,35%), doxycycline (n=14; 5,5%) and aztreonam (n=12; 4,76%). The most frequently used PTs were drug ineffective (n=71; 28%), pathogen resistance (n=14; 5%) and drug resistance (n=13; 13%). A total of 119 reports (74%) suggested use-related issues. Watch antibiotics were in 54% of the reports and Reserve antibiotics were in 19%. In the Watch group, “Off label use” and “Product use in unapproved indication” were the most frequent PTs and majority of reports on Reserve antibiotics were coded as “Off label”. (4) Conclusions: Addressing AMR using the PV methods will provide an opportunity for PV expansion and could encourage further investment in both in AMS programs and PV systems.

Assessment of knowledge, attitude and practice of pharmacovigilance and adverse drug reactions reporting among the community pharmacies in Dharan

<p class="abstract"><strong>Background:</strong> Community pharmacist’s (CPs) knowledge, attitude and practice (KAP) of pharmacovigilance and adverse drug reactions (ADR) play a vital role in preventing harmful effects of medicine. The objective was to assess the KAP of pharmacovigilance and ADR reporting among CP.</p><p class="abstract"><strong>Methods:</strong> A cross-sectional study was carried out among 132 CP in Dharan between February-March 2019 by using a self-administered 25-item semi-structured questionnaire. The KAP score was categorized as good (score 13-25) and poor (score 0-12). The descriptive statistics were calculated using Microsoft excel 2010.</p><p class="abstract"><strong>Results:</strong> Out of 132 pharmacies, only 77 responded giving a response rate of 58.3%. There were 45 (58.4%) male. Majority of the participants (45, 58.4%) had completed diploma in pharmacy course. Only 23 (29.9%) respondents gave the correct responses regarding the definition of pharmacovigilance and 23.4% were aware of the national pharmacovigilance centre. 50.9% agreed that reporting of ADRs is a part of pharmacist duty and it was important to report ADRs and was leading cause of hospitalization. Sixty three (81.8%) participants had never ever been trained on how to report ADR. Seventy (90.9%) participants were willing to report ADR, however, 51 (66.2%) had never seen the ADR reporting form. Only 3 (3.9%) participants had good KAP score (23.33±1.54).</p><p class="abstract"><strong>Conclusions:</strong> Despite of relatively better attitude towards pharmacovigilance and ADR reporting, they had a limited knowledge and practice with regard to ADR reporting and pharmacovigilance. The study findings highlights the need to strengthen the community pharmacovigilance program for safer medication use at the community level.</p>

Cardiovascular adverse effects of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients: Cases from a single pharmacovigilance centre

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients.