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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]

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]

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]

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]

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]

Drug safety is a significant concern in many countries, as side effects (AE) and adverse drug reactions (ADR) have caused many deaths worldwide. One of the reasons is the low contribution of pharmacists in spontaneously reporting AE/ADR. This study aims to develop a questionnaire to assess factors that correlate with spontaneous reporting by pharmacists. A questionnaire pilot was tested on 30 pharmacist respondents who worked in type C hospitals in Surabaya and Sidoarjo, Indonesia. Respondents' responses were then evaluated for face validity, construct validity, and reliability. The results showed that the face validity of the questionnaire was ideal. Then, the results of the construct validity of the knowledge section using point biserial correlation showed that two items were invalid because the r-value was smaller than the r-table (r = 0.361). Then, construct validity uses the factor analysis method for psychological, environmental, and practical variables by paying attention to the Kaiser-Mayer-Olkin Measure (KMO) value, which must be greater than 0.5, the significance of the Bartlett test, which must be less than 0.05 and the factor loading value which conditions must be greater than 0.5. As a result, most of the psychological, environmental, and practical variables show valid and reliable results. However, further consideration should be given to eliminating some items that do not meet the requirements. In conclusion, this validated questionnaire can be used to obtain additional information regarding factors influencing spontaneous reporting by pharmacists.

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 ¾ 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.

We aimed to identify whether a spontaneous reporting system (SRS) in Croatia could timely identify and confirm signals for COVID-19 vaccines. Post-marketing spontaneous reports of adverse drug reactions (ADRs) following COVID-19 immunisation reported to the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) were extracted and analysed. 6624 cases reporting 30 655 ADRs following COVID-19 immunisation were received from 27th December 2020 to 31st December 2021. Available data in those cases were compared with data available to the EU network at the time when signals were confirmed and minimisation measures were implemented. 5032 cases, reporting 22 524 ADRs, were assessed as non-serious, and 1,592 cases, reporting 8,131 ADRs as serious. The most reported serious ADRs, which were listed in the MedDRA Important medical events terms list, were syncope (n = 58), arrhythmia (n = 48), pulmonary embolism (n = 45), loss of consciousness (n = 43), and deep vein thrombosis (n = 36). The highest reporting rate had Vaxzevria (0.003), followed by Spikevax and Jcovden (0.002), and Comirnaty (0.001). Potential signals were identified, however, they couldn’t be timely confirmed solely on cases retrieved by SRS. In order to overcome the limitations of SRS, active surveillance and post-authorisation safety studies of vaccines should be implemented in Croatia.

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.

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: Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs. Objectives: We aim to evaluate Individual Case Safety Reports (ICSRs) of ICIs-induced cardiac arrhythmias and compare the reporting frequency of cardiac arrhythmias among ICIs. Methods: ICSRs were retrieved from the European Pharmacovigilance database (Eudravigilance). ICSRs were classified based on the ICI reported (pembrolizumab, nivolumab, atezolizumab, ipilimumab, durvalumab, avelumab, cemiplimab, and dostarlimab). If more than one ICI was reported, the ICSR was classified as a combination of ICIs. ICSRs of ICI-related arrhythmias were described and the reporting frequency of cardiac arrhythmias was assessed by applying the reporting odds ratio (ROR) and its 95 % confidence interval (95 %CI). Results: A total of 1262 ICSRs were retrieved, of which 147 (11.65 %) were related to combinations of ICIs. A total of 1426 events of cardiac arrhythmias were identified. The three most reported events were atrial fibrillation, tachycardia, and cardiac arrest. Ipilimumab was associated with a reduced reporting frequency of cardiac arrhythmias compared to all other ICIs (ROR 0.71, 95 %CI 0.55–0.92; p = 0.009). Anti-PD1 was associated with a higher reporting frequency of cardiac arrhythmias than anti-CTLA4 (ROR 1.47, 95 %CI 1.14–1.90; p = 0.003). Conclusion: This study is the first comparing ICIs for the risk of cardiac arrhythmias. We found that ipilimumab was the only ICI associated with a reduced reporting frequency. Further high-quality studies are needed to confirm our results.

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]

There is considerable interest worldwide in developing safe and effective vaccines against COVID-19. Pharma-covigilance of adverse events following immunisation (AEFIs) is a key to making informed decisions regarding the global COVID-19 vaccination campaign. In the Kyrgyz Republic, there have been developed a national immunisation information system (IIS) for automated recording of vaccines, vaccinated persons, and AEFIs and a mobile application for AEFI reporting, called Den Sooluk.The aim of the study was to analyse the pattern of AEFIs against COVID-19 in the Kyrgyz Republic.Materials and methods: the study analysed the spontaneous safety reports submitted to the national IIS database through the Den Sooluk mobile application from 29.03.2021 to 25.09.2022.Results: according to the data available by 25.09.2022, the total number of vaccinated people in the country amounted to 2,940,082. At the time, the IIS database included 2111 AEFIs: 1 fatal (and coincidental), 3 severe and 2108 minor ones. AEFIs were more frequent in the young and middle-aged population (81.5%), than in the elderly (18.5%). The following AEFIs were reported: injection site pain (21.25%), fatigue (20.7%), headache (19.8%), body temperature above 38 °C (10.10%), miscellaneous symptoms (5.12%), chills (4.41%), dizziness (4.32%), sore throat (3.36%), myalgia (2.9%), and nausea (2.2%).Conclusions: all COVID-19 vaccines used in the Kyrgyz Republic can be considered adequately safe. Pharmacovigilance of AEFIs is an integral part of the requirements to ensure the safe use of vaccines, and collecting of spontaneous reports on AEFIs supports adequate functioning of the post-marketing surveillance system. It is essential to provide access to electronic information platforms to health professionals and patients in order to ensure vaccination transparency and coordination and enable quick and safe reporting of AEFIs associated with the use of COVID-19 vaccines.

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]

Abstract 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.

(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]

Abstract Background Adverse effects of drugs are often identified after market introduction. Post-marketing pharmacovigilance aims to detect them as early as possible and relies on spontaneous reporting systems collecting suspicious cases. Signal detection tools have been developed to mine these large databases and counts of reports are analysed with disproportionality methods. To address disproportionality method biases, recent methods apply to individual observations taking into account all exposures for the same patient. In particular, the logistic lasso provides an efficient variable selection framework, yet the choice of the regularization parameter is a challenging issue and the lasso variable selection may give inconsistent results. Methods We propose a new signal detection methodology based on the adaptive lasso. We derived two new adaptive weights from (i) a lasso regression using the Bayesian Information Criterion (BIC), and (ii) the class-imbalanced subsampling lasso (CISL), an extension of stability selection. The BIC is used in the adaptive lasso stage for variable selection. We performed an extensive simulation study and an application to real data, where we compared our methods to the existing adaptive lasso, and recent detection approaches based on lasso regression or propensity scores in high dimension. For both studies, we evaluate the methods in terms of false discoveries and sensitivity. Results In the simulations and the application, both proposed adaptive weights show equivalent or better performances than the other competitors, with an advantage for the CISL-based adaptive weights. CISL and lasso regression using BIC are solid alternatives. Conclusion Our proposed adaptive lasso is an appealing methodology for signal detection in pharmacovigilance. Although we cannot rely on test theory, our approaches show a low and stable False Discovery Rate in all simulation settings. All methods evaluated in this work are implemented in the adapt4pv R package.

Chile has a passive surveillance system of adverse events following immunization (AEFI) that allows monitoring and evaluating the safety profile of the vaccines administered. Between 2018 and 2019, the National Immunization Program (NIP) changed from a pentavalent whole-cell pertussis vaccine (wP) to a hexavalent (DTaP-IPV-HepB-Hib) acellular pertussis vaccine (aP) for children

This study assessed adverse events following immunizations (AEFIs) reported on COVID-19 vaccines in VigiAccess and determined the reporting trends across all continents of the world. The study was cross-sectional quantitative in design. VigiAccess was searched on 10 November 10 2021 for reported adverse events following the introduction of COVID-19 vaccines. After entering the search term, “COVID-19 vaccines” in VigiAccess, AEFIs associated with nine approved brands of COVID-19 vaccines had been documented in the database. Data were captured among age groups, sex, and continents of the world and analyzed using Statistical Package for Social Sciences (SPSS) version 25. Overall, 2,457,386 AEFIs had been reported in VigiAccess at the time of the search. No causal associations could be established between the vaccines and the AEFIs. The public accessing VigiAccess data should therefore be made aware of this in order to not falsely attribute AEFIs to COVID-19 vaccines when assessing the database.

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]

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]

Introduction: Most evidence of adverse drug events (ADEs) comes from hospitals as the risks associated with hospital care are higher. However, underreporting of ADEs is a critical problem in all healthcare settings. This is important in sub-Saharan African countries including Ghana with limited resources and a high prevalence of both infectious and non-infectious diseases. Consequently, this study sought to determine the annual prevalence of spontaneously reported ADEs using 6-year reports and factors associated with the occurrence of serious ADEs amongst outpatient care settings in hospitals in Ghana to provide future guidance. Methodology: This is a cross-sectional study using duplicates of the Ghana Food and Drugs Authority adverse event forms retrieved from three outpatient care settings submitting their reports to the National Pharmacovigilance Centre in Ghana between 2013 and 2018. Descriptive and bivariate analyses were performed. Results: Overall, 93 spontaneously reported cases of ADEs were identified during the study period. The annual prevalence rate was 192 reports/1000,000 population amongst our study population, and the rate of serious ADE was 35.48% (95% confidence interval: 25.83%–46.09%). Serious ADEs were associated with the type of indication for which the drug was prescribed (P = 0.048), the duration of the ADE (P = 0.047) and the need to administer treatment for the ADE at the reporting facility (P = 0.017). Conclusion: Early spontaneous reporting of ADEs at outpatient settings is essential. Patient and provider education and awareness of potential ADEs must be intensified for early identification and reporting.

The aim of this study was to investigate the characteristics of medication errors (MEs) and adverse drug reactions (ADRs) using data from the spontaneous reporting system, which is helpful to understand the actual situation of MEs in China. Data from 2015 in a south distinct in Shanghai were gathered from the spontaneous reporting system and analyzed. The general information, cause of errors, severity, primary diseases, involved system and organs, symptoms, and suspected drugs were investigated. A total of 1290 adverse drug events (ADEs), including 1079 ADRs and 211 MEcs (MEs causing ADE), were reported. Older patients suffered from both ADRs and MEcs (age distribution and dosage form were different between ADRs and MEcs). The main causes of errors were inappropriate usage and dosage of drugs and inappropriate indication selection. Most ADR and MEc cases were mild; the possibility of developing a severe adverse event was quite low. The distribution of the top 10 system and organs, and symptoms involved was significantly different between ADRs and MEcs, with J01 drugs (antibacterials for systemic use) being the leading cause in both. Our results suggested that a direct analysis of data from the spontaneous reporting system is a reliable, and convenient method to investigate MEs and ADRs, despite the existing limitations, and contributes to further understanding the current situation of MEs and ADRs in China.

Abstract 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

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Lu, Song and Liu.)

Background: The high incidence of adverse drug reactions (ADRs) in children is of global concern. Enhancing the reporting of ADRs could contribute to making safer medicines available to children. Aim: To assess parents’ awareness of reporting ADRs and their knowledge on the reporting procedures in South Africa. Setting: South African parents with online access. Method: A quantitative descriptive study was conducted based on an anonymous voluntarily web-based self-administered questionnaire that was distributed through Facebook® and LinkedIn™ to parents in South Africa. Results: The questionnaire was completed voluntarily by 206 respondents. The majority of participants (70.9%) were aware of the term ADR. Significant associations between not being aware of the term ADR and single marital status, lower education level, not having private medical aid and accessing public clinics for medical services were found. The majority (66.5%) of participants did report an ADR to a healthcare professional whilst only 15% reported it to a product manufacturer. More than half of the participants (58.7%) knew how to report ADRs whilst 72.8% knew what type of ADRs to report. Almost a third (32.5%) did not know where more information on ADR reporting could be found or how ADRs could be reported (31.5%). Conclusion: The majority of the respondents were aware of the term ADR, indicative of a good knowledge basis on which ADRs to report and the importance of reporting ADRs. However, gaps in the respondents’ knowledge were identified which highlighted specific groups of individuals to be targeted to increase ADR awareness and improve the knowledge on the reporting process.

(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.

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]

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]

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Abstract Background Adverse drug reaction (ADR) reporting practices by health care professionals remain poor. Over-the-counter (OTC) drugs are perceived as safe; however, they can also cause ADRs. The objective of this study was to analyze ADR reporting for OTC drugs in a 10-year period, in order to evaluate frequency of ADRs, population that ADRs most affect and reporters of ADRs of OTC drugs in Croatia. Methods Spontaneously reported ADRs of non-analgesic OTC drugs, collected from January 2008 to December 2017 were analyzed. Data was obtained from Agency for Medicinal Products and Medical Devices of Croatia (HALMED). Results There were 547 ADRs of OTC drugs reported in total and an increase in number of reports through the years was observed. Pharmacists reported 45.4% of all ADRs, and were most frequent reporters (p

Few data are available on the clinical impact of drug–drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Our objective was to describe the characteristics of ADRs resulting from DDIs reported to the French Pharmacovigilance system and to identify the drugs most often implicated in these ADRs. Considering all ADR reports from January 01, 2012, to December 31, 2016, we identified all cases of ADR resulting from a DDI (DDI-ADRs). We then described these in terms of patients’ characteristics, ADR seriousness, drugs involved (two or more per case), and ADR type. Of the 4,027 reports relating to DDI-ADRs, 3,303 were related to serious ADRs. Patients with serious DDI-ADRs had a median age of 76 years (interquartile range: 63–84); 53% were male. Of all serious DDI-ADRs, 11% were life-threatening and 8% fatal. In 36% of cases, the DDI causing the ADR involved at least three drugs. Overall, 8,424 different drugs were mentioned in the 3,303 serious DDI-ADRs considered. Altogether, drugs from the “antithrombotic agents” subgroup were incriminated in 34% of serious DDI-ADRs. Antidepressants were the second most represented therapeutic/pharmacological subgroup (5% of serious DDI-ADRs). Among the 3,843 ADR types reported in the 3,303 serious DDI-ADRs considered, the most frequently represented were hemorrhage (40% clinical hemorrhage; 6% biological hemorrhage), renal failure (8%), pharmacokinetic alteration (5%), and cardiac arrhythmias (4%). Hemorrhagic accidents are still an important part of serious ADRs resulting from DDIs reported in France. The other clinical consequences of DDIs seem less well identified by pharmacovigilance. Moreover, more than one-third of serious DDI-ADRs involved at least three drugs.

Background: The high incidence of adverse drug reactions (ADRs) in children is of global concern. Enhancing the reporting of ADRs could contribute to making safer medicines available to children. Aim: To assess parents' awareness of reporting ADRs and their knowledge on the reporting procedures in South Africa. Setting: South African parents with online access. Method: A quantitative descriptive study was conducted based on an anonymous voluntarily web-based self-administered questionnaire that was distributed through Facebook® and LinkedIn™ to parents in South Africa. Results: The questionnaire was completed voluntarily by 206 respondents. The majority of participants (70.9%) were aware of the term ADR. Significant associations between not being aware of the term ADR and single marital status, lower education level, not having private medical aid and accessing public clinics for medical services were found. The majority (66.5%) of participants did report an ADR to a healthcare professional whilst only 15% reported it to a product manufacturer. More than half of the participants (58.7%) knew how to report ADRs whilst 72.8% knew what type of ADRs to report. Almost a third (32.5%) did not know where more information on ADR reporting could be found or how ADRs could be reported (31.5%). Conclusion: The majority of the respondents were aware of the term ADR, indicative of a good knowledge basis on which ADRs to report and the importance of reporting ADRs. However, gaps in the respondents' knowledge were identified which highlighted specific groups of individuals to be targeted to increase ADR awareness and improve the knowledge on the reporting process. [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]

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.

Context The adverse drug reactions (ADRs) are of great concern for any health care set ups as they directly or indirectly cost in terms of disability, prolongation of hospital stay, or even death. Hence, regular and timely reporting of ADR is of great importance, especially in treating doctors and nursing staff. Aims The main aim of this study was to assess the knowledge, attitude, and practice (KAP) of ADR reporting among doctors and nurses of tertiary care teaching hospital. Settings and design This was a prospective, cross-sectional questionnaire-based study that included 50 doctors and 50 nurses from the clinical departments of rural tertiary care teaching hospital. Patients and methods A self-developed, prevalidated questionnaire consisting of good mixture of open-ended and close-ended questions was used to obtain data, focusing on KAP of ADR reporting. The filled questionnaires were collected from the participants. Statistical analysis The collected data was analyzed using statistical package for the social sciences, version 22. Results The results obtained were of mixed nature. But the overall KAP pertaining to ADR reporting was statistically on a higher side in the doctors' group as compared to nursing staff group. Conclusions The study reveals that both doctors and nursing staff are aware of ADR reporting; their attitude toward ADR reporting is right, but it is not reflected when it comes to actual reporting. The issues related to under reporting and lack of knowledge about the reporting system are clearly evident. Hence, creating an awareness on ADR reporting and sensitizing can aid in improving spontaneous reporting.

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.

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]

The aim of this study was to investigate the characteristics of medication errors (MEs) and adverse drug reactions (ADRs) using data from the spontaneous reporting system, which is helpful to understand the actual situation of MEs in China. Data from 2015 in a south distinct in Shanghai were gathered from the spontaneous reporting system and analyzed. The general information, cause of errors, severity, primary diseases, involved system and organs, symptoms, and suspected drugs were investigated. A total of 1290 adverse drug events (ADEs), including 1079 ADRs and 211 MEcs (MEs causing ADE), were reported. Older patients suffered from both ADRs and MEcs (age distribution and dosage form were different between ADRs and MEcs). The main causes of errors were inappropriate usage and dosage of drugs and inappropriate indication selection. Most ADR and MEc cases were mild; the possibility of developing a severe adverse event was quite low. The distribution of the top 10 system and organs, and symptoms involved was significantly different between ADRs and MEcs, with J01 drugs (antibacterials for systemic use) being the leading cause in both. Our results suggested that a direct analysis of data from the spontaneous reporting system is a reliable, and convenient method to investigate MEs and ADRs, despite the existing limitations, and contributes to further understanding the current situation of MEs and ADRs in China. [ABSTRACT FROM AUTHOR]

Abstract 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

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.

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]

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]