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Introduction: Vascular endothelial growth factor (VEGF) is key to wet age-related macular degeneration (wAMD). Anti-VEGF drugs are the main treatment in clinics. This study assessed ocular adverse events (AE) from anti-VEGF drugs in VigiAccess, WHO's database, and compared adverse drug reaction (ADR) profiles of four drugs to aid personalized treatment choices for optimal benefit and safety. Methods: The design was a descriptive retrospective study. We observed four anti-VEGF drugs commonly used in the clinical treatment of wAMD, and their ADR reports came from WHO-VigiAccess. The collected data included the age group, gender, and regional data, as well as the data of disease systems and symptoms caused by ADR recorded in the annual ADR reports and reports received by the WHO. We observed the overall characteristics of the ADR reports of these drugs, then explored the distribution of 27 SOCs of these drugs. Subsequently, we compared the most common ocular ADRs of the drugs. Finally, we compared the commonalities and differences of ocular ADRs related to the drugs. Results: Overall, 57,779 AE associated with the four anti-VEGF drugs were reported. The results showed that the number of females experiencing ADRs (67.83%) was significantly higher than males (32.17%), the age group with the highest reported incidence was over 75 years old. More than half of the ADR reports came from the Americas (50.86%). The five most common types of AE were: eye disorders (43.56%), general disorders and administration site conditions (34.47%), injury poisoning and procedural complications (13.36%), infections and infestations (11.61%), nervous system disorders (9.99%). Compared with the other three inhibitors, brolucizumab had a significantly higher rate of ocular ADR reports. The most common ocular ADRs of these four anti-VEGF drugs were mostly related to visual impairment, vision blurred, and blindness. However, there is still a disparity of ADRs between different drugs. Conclusion: The presence of ocular AEs when using anti-VEGF drugs to treat wAMD in clinical practice should attract clinical attention. Clinicians should use these expensive drugs more rationally based on the characteristics of ADRs and develop personalized treatment plans for patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Understanding knowledge and attitudes of health care professionals (HCPs) towards adverse drug reaction (ADR) reporting can inform educational interventions promoting ADR reporting. OBJECTIVE: To explore knowledge, attitudes, practice, and barriers of local HCPs towards ADR reporting. METHODS: Focus groups involving HCPs from different settings were organized to help develop a questionnaire. The questionnaire was validated and disseminated to pharmacists, physicians, dentists and nurses practicing in Malta. A review of ADR reports reported in Malta from 2004 to 2021 was carried out to contextualise questionnaire findings. RESULTS: Overall, HCPs (n = 374) had good knowledge on pharmacovigilance and a positive attitude towards ADR reporting however nurses were found to be less knowledgeable than physicians, dentists, and pharmacists. The main barrier for not reporting ADRs was difficulty to understand whether an adverse event occurred (n = 187). A total of 2581 ADR reports were reported in Malta. Among HCPs, physicians and dentists reported most ADRs (1060 reports), followed by pharmacists (307 reports) and nurses (257 reports). CONCLUSION: Further ADR educational and promotional efforts are needed to increase awareness on the importance of quality ADR reporting and increase the number of ADR reports reported by local HCPs. [ABSTRACT FROM AUTHOR]

Introduction: Phytopharmaceutical products are successfully used for acute respiratory infections and may therefore be promising candidates for adjuvant symptomatic treatment of COVID-19. In vitro and clinical studies suggest that the proprietary Pelargonium sidoides DC. root extract EPs 7630 has antiviral and immunomodulatory properties, and effects on SARS-CoV-2 propagation have been shown in vitro. Medicinal products containing the extract have been approved for the symptomatic treatment of acute viral respiratory tract infections. Methods: We present a retrospective review of case reports submitted spontaneously to the pharmacovigilance database of the manufacturer of EPs 7630 and containing information on the off-label use of the extract for the treatment and prophylaxis of COVID-19 and of post-COVID-19 syndrome. Eligible case reports were identified by automated database searches. Results: Forty-four case reports filed between December 2019 and February 2023 were eligible for analysis. More than - described the use of EPs 7630 for treatment of COVID-19 while the remaining reports referred to the treatment of post-COVID-19 syndrome or to COVID-19 prophylaxis. 15/22 cases which reported on treatment duration indicated an intake of EPs 7630 for up to 7 days. Five case reports indicated the use of EPs 7630 as COVID-19 monotherapy while 14 indicated a combination treatment with other drugs. All 28 cases that reported on treatment outcome characterized the patients as improved. Thirty case reports (68%) did not indicate any complications. The most frequent suspected adverse reactions were gastrointestinal complaints and hypersensitivity reactions, both of which may occur as known adverse effects of EPs 7630. No unexpected adverse reactions were observed. Conclusion: Reported cases confirm that there was a certain off-label use of EPs 7630 for COVID-19 in the market. Even though no formal conclusions about the efficacy of EPs 7630 in COVID-19 can be drawn, a beneficial effect would be explainable by the pharmacological profile of the extract. Further assessment of the effects of EPs 7630 in COVID-19-related indications therefore appears to be both justified and promising, particularly as the available case reports did not give rise to any safety concerns also in this patient group. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to describe the knowledge, attitudes and practices of Adverse Drug Reactions (ADR) reporting among healthcare professionals at Teaching Hospital Karapitiya (THK), a tertiary care hospital in Sri Lanka. Methodology: A descriptive cross-sectional study was conducted at THK. The healthcare professionals working in THK who were available during the study period were invited to the study. A self-administered pre-tested questionnaire was administered to the participants. Respondents were evaluated for their knowledge, attitudes and practices related to ADR reporting. The data were analyzed using SPSS statistical software. Results: Of the total 444 respondents, 31% were doctors and 69% were nurses. The majority of respondents, 90% (n = 400) were aware of the term ADR, while 64.8% (n = 288) could correctly define it. Among the respondents, 30.8% (n = 137) knew about the types of ADR and only 15.5% (n = 70) were able to mention a drug that is banned due to ADR correctly. Among the respondents, only 38.7% (n = 172) were aware of a formal process of reporting ADR and, only 35.3% (n = 157) stated that they had seen the ADR reporting form. Further, only 33.7% (n = 150) respondents have recognized ADR during their clinical practice and only a small proportion 18.2% (n = 81) have ever reported an ADR during their practice. Regarding attitudes toward ADR reporting, overall 84.1 (n = 373) had positive attitudes toward ADR reporting, while 13.54% (n = 60) of them stayed neutral and 2.25% (n = 10) had negative attitudes toward ADR reporting. Conclusions: Although the majority were aware of ADR, the knowledge and practices regarding spontaneous reporting of ADR are inadequate. However, most respondents have shown a positive attitude toward ADR reporting. A sincere and sustained effort should be made by concerned bodies to enhance the healthcare professionals' knowledge, attitudes, and practices regarding ADR reporting. [ABSTRACT FROM AUTHOR]

Sudden sensorineural hearing loss (SSNHL), a rare audiological condition that accounts for 1% of all cases of sensorineural hearing loss, can cause permanent hearing damage. Soon after the launch of global COVID-19 vaccination campaigns, the World Health Organization released a signal detection about SSNHL cases following administration of various COVID-19 vaccines. Post-marketing studies have been conducted in different countries using either pharmacovigilance or medico-administrative databases to investigate SSNHL as a potential adverse effect of COVID-19 vaccines. Here, we examine the advantages and limitations of each type of post-marketing study available. While pharmacoepidemiological studies highlight the potential association between drug exposure and the event, pharmacovigilance approaches enable causality assessment. The latter objective can only be achieved if an expert evaluation is provided using internationally validated diagnostic criteria. For a rare adverse event such as SSNHL, case information and quantification of hearing loss are mandatory for assessing seriousness, severity, delay onset, differential diagnoses, corrective treatment, recovery, as well as functional sequelae. Appropriate methodology should be adopted depending on whether the target objective is to assess a global or individual risk. [ABSTRACT FROM AUTHOR]

Background: Medication errors (MEs) are a major public health concern which can cause harm and financial burden within the healthcare system. Characterizing MEs is crucial to develop strategies to mitigate MEs in the future. Objectives: To characterize ME‐associated reports, and investigate signals of disproportionate reporting (SDRs) on MEs in the Food and Drug Administration's Adverse Event Reporting System (FAERS). Methods: FAERS data from 2004 to 2020 was used. ME reports were identified with the narrow Standardised Medical Dictionary for Regulatory Activities® (MedDRA®) Query (SMQ) for MEs. Drug names were converted to the Anatomical Therapeutic Chemical (ATC) classification. SDRs were investigated using the reporting odds ratio (ROR). Results: In total 488 470 ME reports were identified, mostly (59%) submitted by consumers and mainly (55%) associated with females. Median age at time of ME was 57 years (interquartile range: 37–70 years). Approximately 1 out of 3 reports stated a serious health outcome. The most prevalent reported drug class was "antineoplastic and immunomodulating agents" (25%). The most common ME type was "incorrect dose administered" (9%). Of the 1659 SDRs obtained, adalimumab was the most common drug associated with MEs, noting a ROR of 1.22 (95% confidence interval: 1.21–1.24). Conclusion: This study offers a first of its kind characterization of MEs as reported to FAERS. Reported MEs are frequent and may be associated with serious health outcomes. This FAERS data provides insights on ME prevention and offers possibilities for additional in‐depth analyses. [ABSTRACT FROM AUTHOR]

Adverse Drug Reactions (ADRs) pose a challenge for medical doctors (MDs) and other healthcare professionals (HCPs). Serious ADRs increase patient morbidity and mortality and generate a large financial footprint on healthcare costs. Statistics show that about 6% of hospitalizations are due to ADRs and over 50% of them could be avoided. Two years after introducing the pharmacovigilance (PhV) requirements in the European Union, national regulatory PhV requirements were published in the Bulgarian pharmaceutical legislation. Nonetheless, MDs' awareness of the PhV topic still remains extremely important due to patient safety. Spontaneous reporting of ADRs is essential to the success of a pharmacovigilance program. Underreporting of ADRs is common, especially among MDs and HCPs. This study aims to analyse the attitude and the knowledge of graduated MDs towards the reporting of ADRs and drug safety in general. In addition, the study aims to examine their opinion, attitude, and recommendations so that reporting of ADRs becomes more regular. [ABSTRACT FROM AUTHOR]

Background: Spontaneous reporting is the most used method to monitor post-marketing safety information. Although patient involvement in spontaneous reporting has increased overtime, little is known about factors associated with patients' adverse drug reaction (ADR) reporting. Aim: To identify and assess the sociodemographic characteristics, attitudes and knowledge that influence spontaneous reporting and the reasons associated with ADR underreporting by patients. Method: A systematic review was conducted according to PRISMA guidelines. A search on the MEDLINE and EMBASE scientific databases was performed to retrieve studies published between 1 January 2006 and 1 November 2022. Studies were included if they addressed knowledge and attitudes associated with ADR underreporting. Results: A total of 2512 citations were identified, of which 13 studies were included. Sociodemographic characteristics were frequently identified with ADR reporting in 6 studies, being age (3/13) and level of education (3/13) the most often reported. Older age groups (2/13) and individuals with higher level of education (3/13) were more likely to report ADRs. Underreporting was shown to be motivated by reasons related to knowledge, attitudes, and excuses. Ignorance (10/13), complacency (6/13), and lethargy (6/13) were the most frequent reasons for not reporting. Conclusion: This study highlighted the scarcity of research conducted with the aim of assessing ADR underreporting by patients. Knowledge, attitudes, and excuses were commonly observed in the decision to report ADRs. These motives are characteristics that can be changed; hence strategies must be designed to raise awareness, continually educate, and empower this population to change the paradigm of underreporting. [ABSTRACT FROM AUTHOR]

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL- 4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab. Methods: Spontaneous reports were used from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities® (MedDRA®). Safety signal strength was assessed by the Reporting Odds Ratio (ROR). Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24-63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4--29.3). Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation. [ABSTRACT FROM AUTHOR]

(1) Background: The purpose of study was to compare the safety profile of glatiramer with natalizumab, alemtuzumab and ocrelizumab in pregnant and lactating women affected by multiple sclerosis (MS). (2) Methods: Individual case safety reports (ICSRs) were retrieved from the European spontaneous reporting system database (EudraVigilance). The reporting odds ratios (RORs) were computed to compare the reporting probability of events between natalizumab, alemtuzumab and ocrelizumab vs. glatiramer. (3) Results: A total of 1236 ICSRs reporting at least one DMT as a suspected drug were selected. More adverse drug reactions (ADRs) unrelated to pregnancy and breastfeeding (n = 1171; 32.6%) were reported than ADRs specific to pregnancy and breastfeeding (n = 1093; 30.4%). The most frequently reported unrelated ADR was MS relapse. Alemtuzumab and natalizumab seem to have a lower reporting probability of MS relapse compared to glatiramer (ROR 0.17, 95% CI 0.07–0.45 and ROR 0.34, 95% CI 0.20–0.57). Among pregnancy- and breastfeeding-related ADRs, the first most reported event was spontaneous abortion (n = 321; 8.9%). Natalizumab and ocrelizumab were associated with a higher reporting probability of spontaneous abortion compared to glatiramer (ROR 2.22, 95% CI 1.58–3.12; ROR 2.18, 95% CI 1.34–3.54, respectively), while alemtuzumab had a lower reporting frequency (ROR 0.32, 95% CI 0.17–0.60). (4) Conclusions: This study did not suggest any strong or new insights for DMTs in this special subpopulation. However, further studies need to be performed. [ABSTRACT FROM AUTHOR]

Aims: During the COVID‐19 vaccination campaigns, the number of reports of menstrual abnormalities increased rapidly. Here, we describe the nature and potential risk factors associated with menstrual abnormalities based on spontaneously reporting data as well as data from a prospective cohort event monitoring (CEM) study as these are poorly studied. Methods: Reports of menstrual abnormalities received by the Netherlands Pharmacovigilance Centre Lareb in the spontaneous reporting system between February 2021 and April 2022 were summarized. In addition, logistic regression analysis was performed on the reported menstrual abnormalities in the CEM study to assess the association between person characteristics, prior SARS‐CoV‐2 infection and use of hormonal contraceptives and the occurrence of menstrual abnormalities after vaccination. Results: We analysed over 24 000 spontaneous reports of menstrual abnormalities and over 500 episodes (among 16 929 included women) of menstrual abnormalities in the CEM study. The CEM study showed an incidence of 41.4 per 1000 women aged ≤54 years. Amenorrhoea/oligomenorrhoea and heavy menstrual bleeding collectively accounted for about half of all abnormalities reported. Significant associations were observed for the age group 25–34 years (odds ratio 2.18; 95% confidence interval 1.45–3.41) and the Pfizer vaccine (odds ratio 3.04; 95% confidence interval 2.36–3.93). No association was observed for body mass index and presence of most comorbidities assessed. Conclusion: The cohort study showed a high incidence of menstrual disorders among women aged ≤54 years, and this observation was supported by the analysis of spontaneous reports. This suggests that a relation between COVID‐19 vaccination and menstrual abnormalities is plausible and should be further investigated. [ABSTRACT FROM AUTHOR]

Introduction: Tumor necrosis factor (TNF) inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol) have revolutionized the treatment of severe immune-mediated inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. This study assessed adverse drug reactions (ADRs) after the use of TNFα inhibitors in VigiAccess of the World Health Organization (WHO) and compared the adverse reaction characteristics of five inhibitors to select the drug with the least risk for individualized patient use. Methods: The study was a retrospective descriptive analysis method in design. We sorted out five marketed anti-TNFα drugs, and their ADR reports were obtained from WHO-VigiAccess. Data collection included data on the age groups, sex, and regions of patients worldwide covered by ADR reports, as well as data on disease systems and symptoms caused by ADRs recorded in annual ADR reports and reports received by the WHO. By calculating the proportion of adverse reactions reported for each drug, we compared the similarities and differences in adverse reactions for the five drugs. Results: Overall, 1,403,273 adverse events (AEs) related to the five anti-TNFα agents had been reported in VigiAccess at the time of the search. The results show that the 10 most commonly reported AE manifestations were rash, arthralgia, rheumatoid arthritis, headache, pneumonia, psoriasis, nausea, diarrhea, pruritus, and dyspnea. The top five commonly reported AE types of anti-TNFα drugs were as follows: infections and infestations (184,909, 23.0%), musculoskeletal and connective tissue disorders (704,657, 28.6%), gastrointestinal disorders (122,373, 15.3%), skin and subcutaneous tissue disorders (108,259, 13.5%), and nervous system disorders (88,498, 11.0%). The preferred terms of myelosuppression and acromegaly were obvious in golimumab. Infliximab showed a significantly higher ADR report ratio in the infusion-related reaction compared to the other four inhibitors. The rate of ADR reports for lower respiratory tract infection and other infections was the highest for golimumab. Conclusion: No causal associations could be established between the TNFα inhibitors and the ADRs. Current comparative observational studies of these inhibitors revealed common and specific adverse reactions in the ADR reports of the WHO received for these drugs. Clinicians should improve the rational use of these high-priced drugs according to the characteristics of ADRs. [ABSTRACT FROM AUTHOR]

Background: Data on traditional medicine-induced cutaneous adverse drug reactions (ADRs) is very scarce. The current secondary analysis based on the WHO database (VigiBase) of individual case safety reports (ICSRs) focuses on the suspected cutaneous ADRs linked to traditional medicines (TMs). Methods: All the ICSRs reported between 1st January 2016 and 30th June 2021 from the UN Asia region in VigiBase where at least one TM was suspected to cause cutaneous ADRs were included in the study. Data regarding demographic details, suspected drug, adverse reaction as per MedDRA term, the seriousness of the reaction, de-challenge, re-challenge, and clinical outcome for suspected cutaneous ADRs associated with TM were obtained from VigiBase and analyzed for frequency of reported events and suspected medicines. Findings: Total 3,523 ICSRs with 5,761 ADRs related to "skin and subcutaneous tissue disorders" were included in the analysis. Amongst these, 6.8% of ICSRs were reported as serious. Pruritus (29.6%), rash (20.3%), urticaria (18.9%), and hyperhidrosis (3.3%) were commonly reported ADRs. Artemisia argyi H.Lév. and Vaniot. (14.9%), Ginkgo biloba L. (5.1%), Vitis vinifera L. (4%), Vitex agnus-castus L. (3.8%), Silybum marianum (L.), Gaertn (3.5%), and Viscus album L. (2.7%) were some commonly suspected TMs for cutaneous ADRs. There were 46 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported with TMs during the study period. Death was reported in 5 ICSRs. Interpretation: TMs are linked with various cutaneous ADRS ranging from pruritus to toxic epidermal necrolysis which may have serious consequences. TMs listed as suspected offending agents in this analysis, should be kept in mind while dealing with suspected cutaneous ADRs. Clinicians should be more vigilant in detecting and reporting events associated with TMs. [ABSTRACT FROM AUTHOR]

Spontaneous reporting is based on the experience of all healthcare professionals (HCPs) but also consumers/non‐HCPs and therefore reveals a broad picture of a drug's adverse reactions. Recent studies found substantial differences between reports from these varying sources including the reports' completeness. Using the example of opioid‐associated abuse, dependence, or withdrawal, this study analyzed the completeness and characteristics of spontaneous reports from Germany focusing on the reporter. Based on EudraVigilance data, we included all cases of abuse, dependence, or withdrawal associated with opioids indicated for pain therapy and filed from Germany until 2018. Completeness and characteristics were analyzed by a reporter (physician, pharmacist, other HCPs, consumers/non‐HCPs) and also by time period to account for other influencing factors. In total, 1721 cases were included, mainly filed by physicians (38.5%) and pharmacists (30.7%). Completeness of demographics varied from 74.5% (other HCPs) to 42.7% (consumers/non‐HCPs). Consumers/non‐HCPs most often provided any indication/comorbidity (75.2%), whereas this was the case for only 20.2% of pharmacists. Large differences between the reporters were found for almost all characteristics. Other HCPs far more often coded a history of drug abuse, dependence, or withdrawal than other reporters (46.9% vs. 11.6%–24.2%, respectively), and fatal outcomes were also mainly filed by other HCPs (68.1% vs. 14.8%–20.4% by all other reporters). Differences in completeness and characteristics were also observed over time. Studies analyzing spontaneous data should consider potential differences between the various reporting groups in terms of completeness and characteristics. Further, the impact of other influencing factors has to be assessed. [ABSTRACT FROM AUTHOR]

Study aim to describe the spontaneous reporting of the adverse drug reactions (ADRs) among the patients admitted to medicine department of a tertiary care hospital. A prospective observational study was conducted over a period of four months at the medicine department. On the daily basis, all the patients aged >18 years admitted to the internal medicine department were followed and analyzed for occurrence of ADRs. Naranjo scale was used to determine causal relationship between the ADRs and suspected drugs. The nature of ADRs and its severity was assessed using the Hartwig scale. A total of 4,530 patients were screened for the ADRs, out of which 90 ADRs were developed in the 89 patients. The overall incidence of ADRs was found to be 1.96% in the studied population. The most common ADRs encountered during the study period were type A (augmented). The least number of ADRs were observed in the age group of 31–40 years. Furthermore, the more significant number of male patients suffered from a severe type of ADRs as compared to females. Sixteen ADRs were of the mucocutaneous type of reaction followed by dizziness in 12 cases. The higher number of patients recovering from the ADRs was in the age group 41–60 years. The outcomes of ADRs were not found to be statistically significant with gender and age groups. There is a strong need to extend the monitoring and reporting of the ADRs to ensure the patient safety. However, the overall incidence of ADRs appeared to be less in our study, highlighting the need for strengthening reporting system of ADRs. The results indicate that elderly patients are at significant risk of developing ADRs. [ABSTRACT FROM AUTHOR]

(1) Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tears) for characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting. (2) Methods: The underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tears). The factors related to the report in spontaneous reporting through statistical tests were also determined. (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tears. Additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females when compared with spontaneous reporting and active surveillance. (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Additionally, since underreporting seems to b selective, the role of certain aspects, such as gender, seriousness, severity, and unexpected ADRs, must be considered in future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Following minor changes of excipients of Levothyrox®, the French Pharmacovigilance Database was overwhelmed by patients' spontaneous reports of adverse drug reactions associated with the new formula. After noticing that most of these reports differed from those related to other drugs, we aimed to characterize their features and compared them with spontaneous reports associated with other chronic treatments as comparators. We randomly sampled patient reports associated with either Levothyrox® new formula (n = 200) or comparator drugs (n = 200) from March 2017 till March 2018 from the National Pharmacovigilance Database. We evaluated the number of incriminated drugs and adverse drug reactions per report and verified whether they were "expected" or not according to the Summary of Product Characteristics. Levothyrox®‐associated reports included, on average, more adverse drug reactions (8 ± 4) than comparators (2 ± 2, P < 0.01) and mentioned mostly one drug (98.5% of reports), whereas comparators mentioned two at least (P < 0.001). The quantitative distribution of adverse drug reactions per report differed quite significantly, appearing almost Gaussian for Levothyrox® whereas Poisson‐like for comparators (P < 0.0001). Age did not differ significantly in the two groups (54.2 vs. 49.7, NS), but female predominated in Levothyrox® group (94.5%) as compared with comparators (60.8%, P < 0.001). A mere third of the Levothyrox®‐associated adverse drug reactions were deemed "expected," versus two thirds for comparators (P < 0.001). The pattern of spontaneous reports associated with Levothyrox®, whether fueled by media or influenced by social networks, appears atypical, as compared with that of comparators. Such reports, by their abundance, may impair the automatic detection of relevant concomitant signals. [ABSTRACT FROM AUTHOR]

Background/Aim: Adverse drug reactions (ADRs) represent a major concern leading to significant increases in both morbidity and mortality globally. Providing healthcare professionals (HCPs) and patients with real-world data on drug safety is imperative to facilitate informed decisionmaking. The study aimed to determine the feasibility of creating comparative safety charts for medicines by mapping ADR reporting onto prescribing data. Materials and Methods: Data on serious and fatal ADR reports from the Yellow Card database was mapped onto general practice prescription data in England. The rate of serious and fatal ADR reports per million items prescribed was calculated for commonlyprescribed medicines. Results: Quantitative comparative analyses for 137 medicines belonging to 26 therapeutic classes were conducted. Significant differences were observed within most therapeutic classes for the rate of serious and fatal ADR reports per prescribing unit. Conclusion: Despite the limitations of ADR reporting and prescribing databases, the study provides a proof-of-concept for the feasibility of mapping ADR reporting onto prescribing data to create comparative safety charts that could support evidence-based decision-making around formulary choices. [ABSTRACT FROM AUTHOR]

Background: Children and adolescents are at particular risk for adverse drug reactions (ADRs). We investigated physicians' perceptions on ADRs in pediatric routine care. Methods: In this exploratory study from April to November 2020, we invited physicians treating pediatric patients across Germany to complete an online questionnaire consisting mainly of closed questions. Results: Completion rate was 98% (127/129). Of all participants, 23% (29/127) stated they were not able to estimate how many of their pediatric patients experienced ADRs during drug therapy. The remaining physicians estimated that 7.5% (median; Q25/Q75 3%/20%) of their pediatric patients were affected by ADRs. Regarding counseling on ADRs, 61% (77/127) stated they do not ask regularly the extent to which parents want to be informed. In total, 26% (33/127) stated they avoid counseling on ADRs concerning commonly used approved therapies, whereas only 4% (5/127) did so concerning off-label use (P < 0.001). Altogether, 16% (20/127) stated they rather prescribe new medicines as they hope for better effectiveness; 72% (91/127) said they are cautious about doing so owing to yet unknown ADRs. Of all respondents, 46% (58/127) stated they do not report ADRs to the authorities. Concerning the black triangle symbol, a European pharmacovigilance measure, 11% (14/127) stated they knew it and 6% (7/127) stated they reported any suspected ADR for drugs with that symbol. Conclusions: Physicians' perspectives on ADRs were ambivalent: ADRs influenced their parent counseling and drug prescribing; yet, they struggled to estimate the impact of ADRs on their patients and were not aware of specific pharmacovigilance measures. [ABSTRACT FROM AUTHOR]

Objective: Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database. Methods: All ADR reports with DOACs and VKAs as suspected drugs that were entered into the Sicilian SRS database during the period 2001–2019 were selected. In detail, all reports with the following single active substances were included: dabigatran etexilate, rivaroxaban, apixaban and edoxaban; acenocoumarol and warfarin were included as a comparator group. Descriptive statistical methodology was used to evaluate characteristics of the reported cases with a case‐by‐case assessment. Results and Discussion: Out of 521 reports related to anticoagulants, 444 (85.2%) and 77 (14.8%) involved DOACs and VKAs, respectively. DOAC‐related reports were mainly of gastrointestinal disorders. In contrast, VKAs were mostly associated with blood and lymphatic system disorders, injury, investigations and vascular disorders. Many more cases of ADRs in the form of gastrointestinal disorders concerned dabigatran etexilate (n = 179, 73.7%) than the other DOACs, while ADRs in the form of blood disorders were mainly associated with acenocoumarol (n = 27, 57.4%). The most commonly reported Preferred Terms for DOACs were dyspepsia (n = 89, 17.1%), upper abdominal pain (n = 41, 9.2%) and pruritus (n = 26, 5.8%), whereas for VKAs, they were anaemia (n = 21, 27.3%) and hypocoagulable state (n = 18, 3.5%). Potentially interacting concomitant medications particularly included antithrombotic agents (n = 19, 4.3%) for DOACs and proton‐pump inhibitors (PPIs) (n = 37, 48.1%) and antithrombotic agents (n = 13, 16.9%) for VKAs. Conclusion: The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug‐drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs. [ABSTRACT FROM AUTHOR]

Aims: Retroperitoneal fibrosis (RPF) is a rare chronic fibro‐inflammatory disorder that may be secondary to certain drugs, including β‐blocking agents (BBAs). However, their causative role is unclear. We aimed to investigate this association. Methods: Disproportionality analysis was carried out on cases from 1985 to 4 October 2020 in VigiBase, the World Health Organization pharmacovigilance database. The Bayesian‐based IC025 metric and reporting odds ratio were used in order to assess the adverse event signal. We also analysed all published case reports from the literature regarding BBA‐associated RPF to assess the value of suggested supportive clinical evidence. Results: In total, 1599 individual case safety reports of RPF were reported to VigiBase, of which 132 (32%) concerned 16 different single BBA. For 12 of these agents (75%), reporting of RPF was disproportionate, indicating a potential safety signal. Line listing analysis of individual case safety reports showed no consistent time interval from start of BBA to RPF diagnosis (range 0.7–264 mo). Dechallenge was negative or unknown in the majority of cases (74%). In 18 published cases from the literature, time from start of BBA to RPF diagnosis varied widely (range 3–156 mo). BBA were discontinued 6 months before (n = 1) or at the time of RPF diagnosis (n = 17). Most patients (84%) also received RPF specific treatment. Follow‐up duration was short (median 5 mo [range 1–24 mo]) and in most cases (83%) relevant follow‐up data were lacking. Conclusion: Although disproportionality analysis indicated a potential safety signal for RPF associated with BBAs, clinical evidence did not support a cause‐and‐effect relationship. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Biopharmaceuticals improved the prognosis and quality of life of patients with chronic diseases. The aim of our study was to analyse the total reported suspected adverse drug reactions (ADR) and ADRs of reference biologicals and their biosimilars in Slovakia. METHODS: Using data from the State Institute for Drug Control database, we analysed the trends of suspected ADR submitted between 2001-2017 including the registered biosimilars and their reference biologicals: erythropoietin, filgrastim and infliximab. RESULTS: Severe suspected ADR represented 42.95 % from all the reported cases (n=13,462) over the time period 2006-2017 and 54.98 % over 2015-2017 respectively. Reports from 2015-2017 were further analysed. From 4,364 cases, 27 were associated with infliximab and one with erythropoietin. 75 % of these ADR were severe including one death. The difference between the suspected ADR for infliximab reference biological compared to the biosimilar was not statistically significant (p=0.171) after adjustment to the number of prescribed drug units. CONCLUSION: We did not find any evidence of increased risks associated with biosimilars compared to reference biologics. The spontaneous reporting system represents an inexpensive tool of reporting ADRs and should be utilized more frequently by health professionals, but even more importantly, by patients (Tab. 3, Fig. 2, Ref. 30). [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Antimicrobial resistance (AMR) is no longer an expected upcoming threat; it has become a real public health concern, challenging all existing control tools, requiring multidisciplinary innovative solutions. Antimicrobial stewardship (AMS) programs require a set of tools and skills which can be put to service by health systems. However, there is an immense capacity gap between health systems in developed countries compared to developing ones. Systems in developed countries can rely on well-established laboratory services that can carry out microbial cultures and drug susceptibility tests. For many low- and middle-income countries (LMICs) with limited laboratory resources, it will take time and long-term investments to have systems that can timely and reliably perform laboratory-based AMR monitoring. In the meantime, we must explore the possibility of using other indirect measures that can provide estimates of the growing burden of AMR in settings with weak laboratory capacity. Objectives: In this point of view, we describe the potential contribution of the global pharmacovigilance (PV) networkers in the process of mapping and estimating the AMR burden in settings with less laboratory coverage and capacity, within the framework of AMS. Conclusion: The heavy toll caused by AMR will not be brought down by a singular interventional approach, it will require a multidisciplinary and multifaceted set of strategies. Closing the laboratory capacity gap will require tremendous long-term investments, but the AMR data scarcity is a question that cannot wait any longer. The global pharmacovigilance network is a robust scientific community with experience in tracking suspected adverse events caused by new and old medicinal products. As AMR becomes a global health issue, AMS programs need all available tools to address resistance data scarcity and inform appropriate of antimicrobials. The solid global pharmacovigilance infrastructure could play an important role in countries with limited laboratory coverage and capacity. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is limited information on the safety of drugs used for the treatment of COVID-19. Objective: Objective of this study is to describe the pattern of stimulated spontaneous adverse drug reaction (ADR) reports received from healthcare professionals for SARS-CoV-2 positive patients in Ghana and lessons learnt particularly for low- and middle-income countries. Methods: This is a study of individual case safety reports (ICSRs) received from healthcare professionals between 1st April 2020 to 31st July 2020 in SARS-CoV-2 positive patients in Ghana. The ICSRs were retrieved from the SafetyWatch System and descriptive statistics used to describe the ADRs by System Organ Classification and Preferred Term. Results: Information was received from 40 COVID-19 Treatment Centres across the country with 9 centres submitting a total of 53 ICSRs containing 101 ADRs; approximately two ADRs per ICSR. Females accounted for 29(54.7%) of the ICSRs and males 24(45.3%). Newly reported ADRs of interest were one report each of tremor for doxycycline; scrotal pain, dyspnoea, gait disturbances and dysgeusia for chloroquine; and dry throat, hyperhidrosis, restlessness and micturition frequency increased for hydroxychloroquine. A strong spontaneous system with the availability of focal persons at the Treatment Centres played a key role in reporting ADRs during the pandemic. Conclusion: This is the first experience with spontaneous reporting during COVID-19 pandemic in Ghana. The profile of most of the ADRs reported appears consistent with what is expected from the summary of product characteristics. A study with a larger sample size with well-defined denominator in future studies is paramount in determining the relative risk of these medications in SARS-CoV-2 positive patients. [ABSTRACT FROM AUTHOR]

Background: Spontaneous reporting (SR) of adverse drug reactions (ADRs) from patients can be considered as a valuable activity providing both objective and subjective data. However, improving the rate of under-reporting has been a major challenge to ensure successful operation of the SR system. This study aimed to assess knowledge, attitude, and intent to report ADRs and explore the factors contributing to consumers' reporting intent in South Korea.Methods: Self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of consumers using a commercial panel in December 2018. Univariate and multivariate logistic regression analyses were used to explore the factors contributing to the intent to report ADRs by consumers.Results: A total of 1000 respondents were enrolled in the survey; 50.9% were males and the mean age was 44.4 (standard deviation, 13.3) years. While less than 15% of the respondents were aware of the SR system and even fewer (3.4%) had actual experience of SR, however, 59.2% expressed their intent to report ADRs. The positive attitude (adjusted odds ratio [aOR] 3.972, p < 0.001), awareness of the SR system (aOR 2.102, p < 0.01), self-efficacy for SR (aOR 1.956, p < 0.001), and experiences related to ADR counselling with healthcare professionals (OR 2.318, p < 0.001) are the significant factors contributing to reporting intent.Conclusions: Findings of this study highlight the need for increasing the awareness of the SR system among consumers and empowering them to report ADRs by themselves, which would ultimately improve the drug-safety environment. [ABSTRACT FROM AUTHOR]

This paper reports 17 years of passive safety surveillance of routine use of the pediatric hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b-conjugate vaccine (DTPa-HBV-IPV/Hib, Infanrix hexa, GSK). Global post-licensure passive surveillance data collected in GSK's central safety database since DTPa-HBV-IPV/Hib's launch (2000) are described. The most common spontaneously reported adverse events (AEs) after DTPa-HBV-IPV/Hib vaccination in children were fever (reporting rate: 7.74/100,000 doses distributed), crying (2.62/100,000), injection site erythema (1.87/100,000) and swelling (1.28/100,000). A review of extensive limb swelling did not reveal any safety concerns. An observed-to-expected analysis did not show an increased risk of sudden death after DTPa-HBV-IPV/Hib vaccination, in line with previous observations. The analyses confirmed that increases in spontaneous reporting proportions of convulsions with/without fever and hypotonic-hyporesponsive episodes after co-administration of DTPa-HBV-IPV/Hib and 13-valent pneumococcal conjugate vaccine remained small and their clinical significance unknown. The most common vaccination errors were mistakes in the vaccination schedule. Reporting of preparation errors (mostly reconstitution) was low and did not impact the vaccine's benefit-risk profile. Seventeen years of post-licensure experience confirm confidence in the safety profile of DTPa-HBV-IPV/Hib in routine use, with a favorable benefit-risk profile in infants and toddlers. What is the context? The cornerstone of childhood vaccination in many countries worldwide is a vaccine that protects against several diseases: diphtheria, tetanus, whooping cough, hepatitis B, polio and Haemophilus influenzae type b infections (such as meningitis). One of these vaccines (the longest on the market) is called Infanrix hexa; it has been available for infants and toddlers since 2000. After a vaccine is included in a country's routine vaccination program, its safety is constantly checked; this is done in clinical trials and through spontaneous reporting of adverse events after vaccination. It is important to share up-to-date information on the safety of vaccines, particularly since concerns about vaccine safety in parents may lead to lower vaccination rates an disease outbreaks. Here we summarize 17 years of safety data for the Infanrix hexa vaccine. What is new? We analyzed spontaneously reported adverse events after Infanrix hexa vaccinations between 2000 and 2017 The most commonly reported adverse events were fever, crying and injection site redness and swelling An in-depth review of extensive limb swelling after Infanrix hexa vaccination revealed no safety concerns. There was no increased risk of sudden death after Infanrix hexa vaccination, consistent with what was shown in several other studies. As shown previously, seizures were more common when Infanrix hexa was given together with the pneumococcal conjugate vaccine, Prevnar 13, than when it was given alone. What is the take-home message? The large amount of safety data gathered from clinical trials and from spontaneous adverse event reporting during 17 years of routine vaccination with Infanrix hexa supports its continued use in young children. [ABSTRACT FROM AUTHOR]

Purpose The United Kingdom's "Yellow Card Scheme" for reporting of adverse drug reactions (ADRs) has been operating for 50 years, but reporting rates by community pharmacists remain low. The aim of the study was therefore to investigate the views and experiences of ADR reporting by community pharmacists in Wales, with a particular focus on the potential barriers and facilitators to reporting. Methods: Following ethics approval and piloting, a self‐complete questionnaire was mailed to all registered community pharmacies in Wales, UK (n = 713). A follow‐up mailing was sent to nonresponders after 2 weeks. Results: A response rate of 52% (n = 372) was achieved, of whom 57% had never submitted a yellow card. Key barriers to reporting were not seeing ADRs, difficulty identifying the causative drug, not being sure which ADRs to report, and lack of time. Key facilitators were being able to report through dispensary software and having clearer guidelines about what to report. Differences between those who had previously reported ADRs and those who had not suggested lack of confidence and uncertainty about what to report were more of a barrier for nonreporters. Conversely, reporters wanted feedback on reports, ability to keep reports on their dispensary records, and remuneration to aid them with reporting. Conclusions: While the respondents generally expressed positive attitudes towards ADR reporting, a number of barriers and potential facilitators were nevertheless identified. Clearer support and guidance for reporting, such as through a "champions" scheme similar to that run in Welsh hospitals, may help current nonreporters to engage. [ABSTRACT FROM AUTHOR]

Introduction: The panorama of drug-induced ototoxicity has widened in the last decades; moreover, post-marketing data are necessary to gain a better insight on ototoxic adverse drug reactions (ADRs). The aim of this study was to perform an analysis of ADR reports describing drug-induced ototoxicity from the Italian spontaneous reporting system (SRS). Methods: As a measure of disproportionality, we calculated the reporting odds ratios (RORs) and 95% confidence intervals (CIs) with a case/non-case methodology. Cases were all suspected ADR reports regarding drug-induced ototoxicity collected into the Italian SRS from 2001 to 2017. Non-cases included all other ADRs reported in the same period. Results: Of 325,980 reports, 652 included at least one ototoxic ADR, compared with 325,328 non-cases. Statistically significant adjusted RORs were found for drugs for cardiovascular disorders, urologicals, teriparatide, amikacin, prulifloxacin, rifampicin and isoniazid, cisplatin, hormone antagonists, tacrolimus, pomalidomide, tramadol, and antidepressants. Significant adjusted RORs in relation to tinnitus were also observed for doxazosin (ROR 5.55, 95% CI 2.06–14.93), bisoprolol (4.28, 1.59–11.53), nebivolol (8.06, 3.32–19.56), ramipril (3.96, 2.17–7.23), irbesartan (19.60, 9.19–41.80), betamethasone (4.01, 1.28–12.52), moxifloxacin (4.56, 1.71–12.34), ethambutol (12.25, 3.89–38.57), efavirenz (16.82, 5.34–52.96), sofosbuvir/ledipasvir (5.95, 1.90–18.61), etoposide (7.09, 2.63–19.12), abatacept (6.51, 2.42–17.53), indometacin (6.30, 2.02–19.72), etoricoxib (5.00, 2.23–11.23), tapentadol (4.37, 1.09–17.62), and timolol combinations (23.29, 9.53–56.95). Moreover, significant adjusted RORs for hypoacusis regarded clarithromycin (3.95, 1.86–8.40), azithromycin (10.23, 5.03–20.79), vancomycin (6.72, 2.14–21.11), methotrexate (3.13, 1.00–9.81), pemetrexed (4.38, 1.40–13.76), vincristine (5.93, 1.88–18.70), vinorelbine (21.60, 8.83–52.82), paclitaxel (2.34, 1.03–5.30), rituximab (3.20, 1.19–8.63), interferon alfa-2b (17.44, 8.56–35.53), thalidomide (16.92, 6.92–41.38), and deferasirox (41.06, 20.07–84.01). Conclusions: This study is largely consistent with results from literature. Nevertheless, propafenone, antituberculars, hormone antagonists, teriparatide, tramadol, and pomalidomide are unknown for being ototoxic. Hypoacusis after the use of vinorelbine, methotrexate, and pemetrexed is unexpected, such as tinnitus related with etoposide, nebivolol, betamethasone, abatacept, sofosbuvir/ledipasvir, and tapentadol, but these considerations require further investigation to better define the risk due to the paucity of data. Moreover, physicians should be aware of the clinical significance of ototoxicity and be conscious about the importance of their contribution to spontaneous reporting. [ABSTRACT FROM AUTHOR]

To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti‐inflammatory drugs (NSAIDs) according to cyclo‐oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata observed 5 years after market authorization. A case/noncase study was performed among individual case safety reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous reporting database. Cases were ICSRs mentioning angioedema and anaphylactic/anaphylactoid shock conditions, while noncases were ICSRs without HSRs. NSAIDs were categorized into (i) NSAIDs with high COX‐2 selectivity (coxibs), (ii) noncoxib NSAIDs with COX‐2 preference, (iii) NSAIDs with poor selectivity, or (iv) NSAIDs with unknown selectivity. Chemical groups were defined based on the Anatomical Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analysis. We identified 13 229 cases and 106 444 noncases. In the first 5 years after marketing, poor‐selectivity NSAIDs and acetic acid derivatives were associated with the highest ROR of HSRs (age‐ and sex‐adjusted ROR 2.12, 95% CI 1.98–2.28; and ROR 2.21, 95% CI 1.83–2.66, respectively) compared with coxibs, and sulfonamide NSAIDs were associated with the highest ROR of HSRs compared with nonsulfonamide NSAIDs (age‐ and sex‐adjusted ROR 1.38, 95% CI 1.29–1.47). After the first 5 years of marketing, most of the RORs returned to approximately 1. [ABSTRACT FROM AUTHOR]

Background: Personalized feedback received for spontaneous adverse drug reaction (ADR) reports serves as motivation for future reporting and the effectiveness of the feedback is dependent on the medium used in delivering the information. Objective: Explore expectation for feedback from patients on ADR reports submitted to the National Pharmacovigilance Centre (NPvC) in Ghana and the preferred medium for receiving the feedback information. Methods: Cross-sectional study using structured questionnaire administered through face-to-face interview from August to September 2016 to patients selected by convenience sampling. Pearson chi-square (Χ²) or Fisher's exact test was used to determine associations between background variables such as age, gender and level of education. Results: The response rate was 86.7% (n=442). Of the participants interviewed, 96.5% expected to receive feedback for ADR reports submitted. Age and level of education were the two variables significantly associated with patients' expectation for feedback. The preferred medium for receiving feedback in decreasing order of preference were, telephone call (60.4%), mobile phone short messaging services (23.0%), email (8.3%), face-to-face meeting (3.4%), personalized letter (3.4%) and publication in a newsletter (1.4%). Conclusion: Patients' expectation for receiving feedback for ADR reports submitted to the NPvC is in line with modern trends in communication. NPvC should explore these alternatives for providing feedback to patients. This study is limited to what patients' expectations and preferences were for receiving feedback on ADR reports submitted, additional study to further explore the type of information patients expect to be contained in the feedback will be useful to National Pharmacovigilance Centres. [ABSTRACT FROM AUTHOR]

We analyzed the spontaneous adverse event database in Singapore to determine the types of cutaneous adverse drug reactions (CADRs) and causative drugs reported. We selected 10 CADRs-of- interest, and identified the suspected drugs and the characteristics of the at-risk population. ADR reports received from 2006 to 2015 of the system organ class "Skin and Appendages Disorders" were analyzed based on patient demographics, the types of CADRs, suspected drugs, outcome, and latency period. Of the 104 372 reports analyzed, 56.2% involved females and 72.5% involved Chinese patients. The mean age was 41.1 years old. The top CADRs reported were rash (including nonspecified rash, follicular rash, maculopapular rash, and vesicular rash) (67.2%) and angioedema (13.9%). The drugs frequently associated with the CADRs-of- interest include nonsteroidal antiinflammatory drugs and antibiotics with angioedema, iohexol with urticaria, and antiepileptics and allopurinol with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). A subgroup analysis based on age, sex, and race on the 10 CADRs-of- interest showed the following trends in reporting: Alopecia (reported more in females), drug hypersensitivity syndrome (more in males), angioedema (more in younger patients), and photosensitivity (more in older patients). In general, the racial distribution across each CADR-of- interest was consistent with that of Singapore's population, with slight deviations observed for SJS/TEN, photosensitivity and skin discoloration. We analyzed CADR reports from Singapore over 10 years, and identified the types of CADRs reported, and their associated drugs, latency periods and patient characteristics. Such information could add value to healthcare professionals as they assess CADR cases and evaluate suspected drugs. [ABSTRACT FROM AUTHOR]

Paracetamol is a popular and easily available drug which is used world-wide as analgesic, antipyretic agent. Hypersensitivity reactions to this drug involve a wide range of symptoms of various importance for patient management. The EudraVigilance (EV) database serves as a system for monitoring adverse events (AE) due to drug intake. We retrospectively recorded AE reports for “paracetamol” reported from 1 January 2007 to 1 October 2018 which fulfilled the category of “serious” in EV. For further analysis the retrieved AE reports were selected according to the keywords corresponding to hypersensitivity symptoms. We included in the study 4589 AE reports with 9489 particular AEs. 24.2% of all the AE reports concerned children. The most often reported symptoms were “angioedema,” “rash” and “urticaria” (each of them with a frequency of >10% in the AE reports). An important group of AEs were oedema reported as being located in the head, neck or respiratory tract. We recorded 58 AE reports with fatal outcomes, including 9 Stevens-Johnson syndrome/toxic epidermal necrolysis cases (SJS/TEN), 10 anaphylactic reactions, 21 cases of hepatic failure and a further 18 cases which occurred for other reasons. SJS/TEN, acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms were reported 129, 42 and 25 times, respectively. Prodromes and symptoms of potentially life-threating SJS/TEN appeared in 286 of the AE reports. 380 AE reports pointed to a diagnosis of anaphylaxis. To improve patient safety, healthcare professionals, including pharmacists, can identify warning signs of severe hypersensitivity reactions to paracetamol. [ABSTRACT FROM AUTHOR]

Pharmacovigilance is a practice aimed to monitor drug safety in real life conditions and capture adverse drug events during the post marketing phase of drug's life cycle. But under reporting of adverse reactions is a major cause of concern and a threat to the pharmacovigilance systems. The present article looks into the major obstacles affecting the spontaneous reporting of adverse drug reactions (ADRs) in India and the possible solutions. As per available scientific literature, the major impediments to ADR reporting are inadequate knowledge and awareness among health professionals, clinicians' perceptions towards reporting, problems with establishing reporting systems in hospitals and insufficient training to recognize ADRs. Measures to improve the situation include greater involvement of nurses, pharmacists as well as consumers in the reporting of ADRs, making the process simpler and faster through electronic means, introducing educational interventions and training programs for health care providers and spreading awareness about the reporting system amongst caregivers and receivers alike. Providing a momentum to the pharmacovigilance system and ensuring a robust reporting process is a challenge but proper planning, feasible solutions and focussed efforts can help bring about the change ensuring patient safety - the ultimate goal of pharmacovigilance. [ABSTRACT FROM AUTHOR]

Objective: Desloratadine, a third-generation antihistamine, is claimed to cause fewer central nervous system (CNS) adverse drug reactions (ADRs) than antihistamines of the first- and second-generation. While literature is inconclusive regarding the possible CNS effects, symptoms like somnolence and hallucinations are acknowledged ADRs of desloratadine, indeed suggesting some passage of this drug across the blood-brain barrier. Depression is currently not described as an ADR in the approved desloratadine product labelling. Materials and methods: In a joint signal detection workshop with the Uppsala Monitoring Centre and the Netherlands Pharmacovigilance Centre Lareb, case reports of suspected drug-ADR associations were analysed. Results: Forty-nine unique case reports of desloratadine associated with depression or depressed mood were detected in the WHO global ADR database. In these reports, the median time to onset of depression was three days. Most patients recovered after withdrawal of desloratadine, and in five patients the symptoms of depression recurred after re-administration of desloratadine. Conclusion: We hypothesize that desloratadine may enter the CNS and that it hence in rare cases may cause a clinically relevant state of depression, a relation that patients and their treating physicians should be made aware of. [ABSTRACT FROM AUTHOR]

Background: The National Coordination Centre-Pharmacovigilance Programme of India (NCC-PvPI), Indian Pharmacopoeia Commission works under the aegis of Ministry of Health and Family Welfare, Government of India. It promotes patient safety in India and also supports postmarketing surveillance programs. Currently, almost hundred thousand case reports are submitted to NCC-PvPI each year through its 250 ADR Monitoring Centers (AMCs) located across India, and India is the one of the top ten contributor countries under WHO-Uppsala Monitoring Centre since 2012 and start issuing drug safety alerts from March 2016. Aim: This study aims to highlight the drug safety alerts issued by NCC-PvPI from March 2016 to June 2017 and urgent need for further monitoring by adopting targeted spontaneous reporting (TSR) methodology at AMCs and its impact on the NCC's drug safety database, i.e., VigiFlow in India. Methodology: A retrospective analysis was done for the reported unlisted ADRs by various AMCs to PvPI through VigiFlow, i.e., individual case safety report (ICSR) management system at NCC, where these unlisted drug-ADR combinations considered and issued as drug safety alerts for further reporting these to NCC, if any detected at healthcare settings during routine clinical practice by healthcare professionals. Results: From July 2011 to June 2017, NCC-PvPI was collated 250,787 ICSRs and contributed to WHO international drug safety database, i.e., VigiBase, from these ICSRs; NCC-PvPI was issued 56 drug safety alerts from March 2016 to June 2017. Conclusion: In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization. [ABSTRACT FROM AUTHOR]

Purpose We aimed at investigating whether, in Germany, the number of individual case safety reports (ICSR) of confirmed narcolepsy following Pandemrix® vaccination notified to the Paul-Ehrlich-Institut (PEI, German Federal Institute for Vaccines and Biomedicines) was higher than expected when compared with the prepandemic background incidence rates. Methods ICSR of narcolepsy after vaccination with Pandemrix® notified to the PEI until September 2016 were reviewed and validated according to the criteria of narcolepsy defined by the Brighton Collaboration (BC). Cases fulfilling the criteria of BC levels of diagnostic certainty 1 to 4a with symptoms onset after vaccination with Pandemrix® were eligible. Adjustment for underreporting was performed with cases of narcolepsy recruited within the scope of the German Narcolepsy Study using capture-recapture methods. An observed versus expected (OvE) analysis was conducted based on adjusted case numbers using risk windows for symptoms onset within 4 and 6 months following vaccination. Results By the end of September 2016, a total of 85 ICSR of narcolepsy after vaccination with Pandemrix® had been notified to the PEI 52 of which were eligible. The OvE estimates for the 4 and 6 months risk windows were 3.8 (95% CI: 2.6-5.4) and 2.8 (95% CI: 2.0-3.9), respectively. The number of excess cases was higher in children and adolescents (15-fold and 11.7-fold increased OvE estimate) than in adults (2.1-fold and 1.5-fold increased estimate). Conclusions Compared with the prepandemic background incidence rate, the number of incident narcolepsy cases was 3.8-fold and 2.8-fold as high. [ABSTRACT FROM AUTHOR]

Copyright of Mali Médical is the property of Mali Medical, Faculte de Medecine, de Pharmacie et d'Odonto-stomatologie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Little is known about the informativeness of initial patient reports before they are reviewed by a pharmacovigilance centre (PVC). We aim to describe the patterns of patient adverse drug reaction (ADR) reporting in France and estimate the contribution of a review by a PVC assessor on the informativeness of these reports. Methods: A retrospective study was conducted on patient reports between July 2011 and July 2015. Informativeness of 16 key elements of information (including drug start and end date, duration of treatment, time to onset and duration of the ADR, outcome, medical history and concomitant medication) was assessed in initial reports before and after review by a pharmacovigilance assessor. Results: Overall, 240 reports concerning 522 ADR and involving 278 drugs were reported over this 4-year period. Mean number of available key elements of information in initial reports was increased from 11/16 to 15/16 after review of reports by the PVC. Time to onset and duration of the ADR were respectively available in only 51 and 58% of the reports before review compared to 83 and 90% after review. Medical history and concomitant medication were missing in 75% of the initial reports compared to less than 30% of the reports after review. Contacting the reporter enabled an increase of informativeness of most elements of information for more than 90% of the reports. Conclusion: Patient reports often need to be completed on key elements of information that are required to assess reports. Both upstream education of patients and downstream intervention of a pharmacovigilance assessor to complete missing information could help to enhance the informativeness of such reports. [ABSTRACT FROM AUTHOR]

Background: While spontaneous reporting (SR) is one of the important public health activities for community pharmacists to guard patients' safety, very few studies examined educational activities and its effects on knowledge about the SR system in Korea. This study described the association between knowledge of SR and educational activities targeting community pharmacists in Korea. Methods: Self-administered questionnaires were collected between September 1, 2014 and November 25, 2014. The questionnaires addressed sources of SR knowledge (structured educational programs, personal access to educational resources, and information by social network services) and knowledge about the Regional Pharmacovigilance Center designated for community pharmacists, the legal responsibility clause on the serious event reporting, and the reportable items. The association between the knowledge of SR and the educational activities was evaluated using analysis of variance or chi-squared tests. Results: Overall, 766 questionnaires demonstrated that mean age and length of career in community pharmacies was 45.7 years and 15.9 years, respectively. A structured educational program was used in 63.1% of the participants followed by a personal access to educational resources (56.3%). An educational program offered by the Korean Pharmaceutical Association was the most frequently mentioned program (56.8%), and no regional disparity in the program between the metropolitan and rural areas was observed. Pharmacists who had personal access to educational resources identified SR knowledge contents less correctly than those who used a structured educational program or both (p < 0.01). In general, pharmacists' knowledge on reportable items was significantly lower with non-prescription drugs, nutritional supplements, and personal hygiene products as compared to their knowledge on prescription drugs, regardless of the type of education (p < 0.01). Conclusions: Knowledge regarding SR was more likely to increase when a structured educational program was used alone or in combination with other educational methods. Knowledge on reportable items should be reinforced during the continuing education process. [ABSTRACT FROM AUTHOR]

The article discusses knowledge, attitude, and practice (KAP) of pharmacovigilance (PV) to understand drug-related problems among doctors of medical college hospital of Tripura, India. Topics discussed include information on adverse drug reactions (ADRs) , pattern of drug usage in northeastern part of the country, and assessment of attitude about pharmacovigilance among the prescribers.

Purpose To investigate how reporting of adverse drug reactions (ADRs) among adults in Sweden is associated to age and sex, in addition to seriousness of the reaction and drug utilisation. Methods Individual case safety reports (ICSRs) reported by healthcare professionals to the national pharmacovigilance database 2008-2011 were related to defined daily dose (DDD) in the Swedish Prescribed Drug Register (SPDR) for individual's ≥20 years. Data were stratified into five age groups. Crude and adjusted (by age standardisation of prescribed drugs) reporting rate (RR) and reporting rate ratio was evaluated as well as impact of sex-dependent drugs. Results Based on 9898 included ICSRs, the crude results show that overall RR was almost similar for both serious and non-serious reports and indicates highest RR in the youngest age group. Women had higher rates than men, with predominance for non-serious reports, contrary to men who had a higher RR of serious ones. Standardisation led partly to the same result, but age-related distribution was adjusted, with highest overall RR in the oldest age groups. Sex-dependent drugs had marginal impact on the results. Conclusion Age and sex have impact on spontaneous reporting of ADRs. After adjusting for dispensed drugs and by standardisation of age-related differences in prescribed drugs, results indicate that healthcare professionals more frequently reported ADRs for the oldest individuals and for women. Serious reports were more frequently reported for men. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Spontaneous adverse event reports have a high potential for detecting adverse drug reactions. However, due to their dimension, the analysis of such databases requires statistical methods. In this context, disproportionality measures can be used. Their main idea is to project the data onto contingency tables in order to measure the strength of associations between drugs and adverse events. However, due to the data projection, these methods are sensitive to the problem of coprescriptions and masking effects. Recently, logistic regressions have been used with a Lasso type penalty to perform the detection of associations between drugs and adverse events. On different examples, this approach limits the drawbacks of the disproportionality methods, but the choice of the penalty value is open to criticism while it strongly influences the results. In this paper, we propose to use a logistic regression whose sparsity is viewed as a model selection challenge. Since the model space is huge, a Metropolis-Hastings algorithm carries out the model selection by maximizing the BIC criterion. Thus, we avoid the calibration of penalty or threshold. During our application on the French pharmacovigilance database, the proposed method is compared to well-established approaches on a reference dataset, and obtains better rates of positive and negative controls. However, many signals (i.e., specific drug-event associations) are not detected by the proposed method. So, we conclude that this method should be used in parallel to existing measures in pharmacovigilance. Code implementing the proposed method is available at the following url: . [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) in children recorded in national pharmacovigilance databases in high-income countries have been analysed. Nigeria has a population of 31 million children and became a member of the WHO Programme for International Drug Monitoring in 2004 since when it has been submitting reports of suspected ADRs to the WHO Global Individual Case Safety Report database, VigiBase. Objective: To gain information on reported ADRs in Nigerian children aged 0–17 years in VigiBase from 2005 to 2012. Methods: The data were analysed for annual reports, age and sex of patients, type of reporters, suspected drugs and adverse reactions. The most commonly reported ADRs and suspected drugs were ranked, and drugs associated with the fatalities were evaluated. Results: A total of 297 reports of 473 ADRs in 297 children were received from doctors, pharmacists, other health-care professionals and consumers during the period. ADRs were most frequently reported for anti-retrovirals (74, 24%), antibiotics (71, 23%) and anti-malarials (60, 20%). The most frequently reported ADRs were rash (15.2%), fever (10.3%) and pruritus (6.8%). Anti-infective agents were responsible for more than half of the reports. Twenty-one children (7%) died, eight from acute renal failure. Seven of the cases of acute renal failure were associated with contaminated paracetamol/diphenhydramine hydrochloride and herbal medicines used for teething problems. In the majority of cases, the products were contaminated with diethylene glycol. There were 14 cases of Stevens–Johnson syndrome, three of which were fatal. Conclusion: Anti-infective agents (antibiotics, anti-malarials and anti-retrovirals) were associated with a majority of the ADRs. Stevens–Johnson syndrome was the most frequent severe ADR. Some of the fatalities were associated with sub-standard and herbal medications. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe bisphosphonate-related osteonecrosis of the jaw ( BRONJ) in the French national pharmacovigilance database. BRONJ was identified with the standardized MedDRA query ( SMQ) 'osteonecrosis' among all data from 1985 to 31 December 2014. Because this SMQ was not specific to the jaw localization, selection of cases based on anatomy was performed after data extraction. For each case, demographic and medical information was analysed, as well as data about notification (year of notification, year of occurrence, outcome, seriousness). Known associated factors for BRONJ were also documented: dentoalveolar surgery, glucocorticoids, chemotherapy, anti-angiogenics, denosumab. Among 1404 SMQ notifications, 663 were located in the jaws and 629 were associated with bisphosphonate use. BRONJ reported in the database mainly affected women ( n = 443, 71%) with an oncological indication ( n = 440, 70%). BRONJ was considered as serious in 91%. Outcome was unfavourable for 92% of cases. Associated factors were identified for 70% of the patients. A peak of notification was noted in 2014 (13% of all cases), but on analysis by year of occurrence instead of by year of notification, this peak disappeared. SMQ 'osteonecrosis' appears to be an adequate tool to analyse BRONJ in a pharmacovigilance database. [ABSTRACT FROM AUTHOR]

Aim Term and preterm neonates are at high risk for serious adverse drug reactions (ADRs). Methods A descriptive study of reports registered in the French pharmacovigilance database from 1986 to 2012 were obtained. All reports concerning neonates (≤1 month of life) with direct drug exposure were retrieved. Characteristics of the reports, including reported ADR(s), drug(s) and the causality assessment using the French causality assessment method, were described. Results A total of 1688 reports were analyzed and more than half of them were classified as serious ( n = 995). Median age at ADR occurrence was 9 days. Overall, 3127 ADRs were described in these reports in relation to 2238 suspect/interacting drugs. The most commonly reported system organ classes (SOCs) were injury, poisoning and procedural complications (16%), general disorders and administration site conditions (12.5%) and blood and lymphatic system disorders (12%). In the majority of ADRs reported (73%), infants fully recovered and less than 4% of neonates deceased as a consequence of the reported ADR. One out of five ADRs was associated with drug administration errors. Therapeutic classes commonly incriminated were anti-infectives, nervous system and alimentary tract drugs. Substances most frequently related to serious ADRs were zidovudine, ibuprofen and nevirapine. Among the 10 most frequently encountered drug−ADR pairs, two substances were mainly implicated, zidovudine in haematological adverse reactions and phytomenadione in maladministrations. Conclusions Anti-infective drugs, mainly antiretroviral therapy, account for the majority of ADRs reported in neonates. The specific issue of drug maladministration and medication errors remains to be addressed in neonates. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Hospital pharmacists can promote medication safety through spontaneous reporting of adverse drug reactions ( ADRs). However, different educational interventions and different factors (socio-demographic and professional) have been implicated to influence the reporting process. The aims of this study were to assess the impact of pharmacovigilance awareness workshop on knowledge of hospital pharmacists; and to identify the main factors and barriers that influence ADRs reporting. Methods Two validated self-administered questionnaires were distributed to pharmacists attending an awareness workshop (pre and post); and a telephone survey was completed three months after the workshop. ADR reports (yellow cards) received from participating pharmacists were monitored for six months, and analysed for quality (validity and seriousness) and reporter demographic and professional factors. Results Two hundred and eighty-one pharmacists (95.25%) and 270 pharmacists (91.52%) completed pre- and post-workshop questionnaires respectively. A comparison of their knowledge of ADRs to report before and after the workshop showed significant difference ( Wilcoxon test P < 0.05). Two hundred and four pharmacists (72.6%) completed the follow-up questionnaire, with lack of time, administrative barriers and inability to complete patient details being the most frequent reasons for not reporting. A total of 163 yellow cards were received from 49 pharmacists (17.44%) over 6 months, of which 126 reports (77.3%) were serious ADRs. Demographics of reporting pharmacists showed significance for completion of post-graduate studies, ministry of health hospitals and pharmacist post in hospital. Conclusion Despite pharmacists' adequate knowledge after the workshop, they failed to maintain consistent reporting. Addressing the barriers to reporting and the personal factors influencing the process may be needed. [ABSTRACT FROM AUTHOR]

Aim To identify the attitudes and knowledge associated with adverse drug reactions ( ADR) under-reporting by nurses. Background The voluntary reporting system is fundamental for expediting the detection of ADR during post-marketing surveillance. Methods We performed a case-control study. A self-administered questionnaire was sent by mail to 1325 nurses. The knowledge and attitudes related to ADR under-reporting were primarily based on Inman's seven deadly sins. Results The overall response rate was 34.2%. Nurses working in primary care were 12-fold more likely to report an ADR. A change of attitude increased the probability of ADR reporting for:'The belief that the one case an individual nurse might see could not contribute to medical knowledge'; 'I do not know how the information reported is used by the system'; 'I would be more likely to report if the method was easier'; 'I think the most correct way to report is to inform the doctor' and 'I do not have time to think about the involvement of the drug in ADRs'. Conclusions Our study shows that the beliefs of nurses, such as 'one single report would not make any difference' and 'the pharmacovigilance system is very complex', act as a barrier to ADR reporting. Implications for Nursing Management It is important to clarify the ADR reporting procedure and increase the nurses reporting rate. [ABSTRACT FROM AUTHOR]