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SCIENTIFIC RELEVANCE. Pain and pain relief are among the most important problems that arise during medical procedures. Lidocaine is used not only as an anaesthetic during interventions but also as a diluent for other medicinal products. Analysis of adverse drug reactions (ADRs) associated with lidocaine contributes to studying lidocaine toxicity and, as a result, developing measures to reduce side effects.AIM. The authors aimed to conduct a retrospective analysis of spontaneous reports of fatal ADRs associated with lidocaine.MATERIALS AND METHODS. This study analysed spontaneous ADR reports of fatal outcomes associated with lidocaine submitted to the federal ADR database in the Automated Information System of the Federal Service for Surveillance in Healthcare of the Russian Federation (Pharmacovigilance, versions 1.0 and 2.0) from 1 January 2008 to 31 December 2020.RESULTS. The ADR reports included 102 fatal outcomes associated with lidocaine. Most often, lidocaine was prescribed as a local anaesthetic or as a diluent for antibacterials. Studying the administered lidocaine doses, the authors identified several overdose cases. Most life-threatening conditions were due to hypersensitivity reactions of anaphylactic shock (54 cases, 52.9%). Lidocaine administration was accompanied by loss of consciousness, respiratory failure, and cardiac arrest in 10 cases (9.8%). Convulsions were a significant clinical sign in 9 cases (8.8%).CONCLUSIONS. Awareness of the risks of systemic toxic effects of local anaesthetics, including lidocaine, necessitates the practical implementation of certain safety measures, such as allergy skin tests before administration and mandatory monitoring of doses and patients’ well-being after administration.

Post‐marketing pharmacosurveillance is important to reduce harm to patients from marketed drugs. Oral adverse drug reactions (OADRs) are seldom reported and only few OADRs are listed scarcely in summary of product characteristics (SmPC) of drugs. Objective: Structured search for OADRs in the Danish Medicines Agencies database from January 2009 to July 2019. Results: Forty‐eight percent of OADRs were categorized as "serious" where oro‐facial swelling was reported 1041 times, medication‐related osteonecrosis of the jaw (MRONJ) 607 times and para‐ or hypoaesthesia 329 times. Four‐hundred‐eighty OADRs in 343 cases were related to biologic or biosimilar drugs where 73% affected the jawbone as MRONJ. Physician reported 44%, dentists 19% and citizens 10% of OADRs. Conclusions: Health care professionals had a sporadic reporting pattern that seemed to be influenced by the debate in the community and in professional circles but also by the information in the SmPC of the drugs. The results indicate some reporting stimulation of OADRs in relation to Gardasil 4, Septanest, Eltroxin and MRONJ. Eventually the knowledge of OADRs increases but there is a risk of skewed information if reporting is not systematic, reliable and consistent. All healthcare professionals must be educated in spotting and reporting all suspected adverse drug reactions. [ABSTRACT FROM AUTHOR]

Aims: Adverse drug reactions (ADRs) are known to show sex‐specific differences in occurrence and phenotype. The aim of this study was to analyse sex‐specific differences in ADR–drug combinations that required hospitalization based on two different datasets. Methods: We performed a complementary analysis of (i) spontaneously reported (n = 12 564, female = 51.7%) and (ii) systematically collected ADR reports from a prospective multicentre observational study (ADRED, n = 2355, female = 48.2%) from Germany in the ADR database EudraVigilance (EV). Both datasets were analysed separately concerning the suspected drugs, ADRs and ADR–drug combinations more frequently reported for females or males by calculating reporting odds ratios (ROR) with 95% confidence intervals. ADR–drug combinations more frequently reported for either females or males in EV reports were related to prescription data. Finally, the results from both datasets were discussed with regard to their (dis‐)concordance. Results: In both datasets, some antineoplastic agents and nervous system drugs were found to be reported more often for females than males (RORs ranging from 1.5 [1.1–2.1] for quetiapine in spontaneous reports to 41.3 [13.1–130.0] for trastuzumab in spontaneous reports). ADRs of the respiratory system, and haemorrhages were described predominantly for males in both datasets. In spontaneous reports the ADR–drug combination self‐injurious behaviour–quetiapine was more often reported for females without and with consideration of drug prescriptions (ROR: 3.8 [1.3–11.0]). Quetiapine and psychiatric disorders (superordinate level) was exclusively reported for females in ADRED reports. Conclusions: Our results can contribute to raise awareness and further knowledge regarding sex‐specific ADRs. The findings require further in‐depth investigation. [ABSTRACT FROM AUTHOR]

Scientific relevance. Vancomycin and linezolid are the antibacterial agents of choice for severe infections caused by multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). However, few studies have been conducted in Russia to analyse the safety of these medicinal products.Aim. The study aimed to compare the safety of vancomycin and linezolid using the Moscow segment of the Russian Federal Service for Surveillance in Healthcare’s database for adverse drug reaction (ADR) reports.Materials and methods. The study used information from the spontaneous reporting database for 2018–2022, which contained 147 ADR reports for vancomycin (122 reports) and linezolid (25 reports). The authors analysed the ADR distribution and assessed the statistical significance of the identified differences by sex, weight, and age of patients, conditions of medical care, route of administration, single dose, daily dose, therapy duration, ICD-10 codes, ADR severity, and ADR outcome.Results. The distribution of adverse reactions to vancomycin and linezolid by patient age was relatively uniform. Outpatient linezolid was associated with a significantly higher rate of ADRs (3 of 5 reports) than outpatient vancomycin (21 of 129 reports; p=0.0408). For ADR severity, 5 of 20 ADRs reported with linezolid required hospitalisation or prolongation of hospitalisation—considerably more than with vancomycin (16 of 94 reports; p=0.528). The average single dose of vancomycin (794 mg) was higher than that of linezolid (467 mg; p=0.007); the same was noted for average daily doses (1273 mg vs 998 mg; p=0.3664). The mean duration of treatment with linezolid before ADR onset was 5.26 days, which was significantly longer than the mean duration of treatment with vancomycin (2.44 days; p=0.0053). Oral linezolid was associated with a significantly higher ADR rate (4 of 19 cases) than oral vancomycin (5 of 96 cases; p=0.0027).Conclusions. The ADRs observed with vancomycin and linezolid were predictable and class-specific. According to the results of the ADR report analysis, adverse reactions to vancomycin and linezolid were associated with different factors. Similar results of the literature analysis confirmed this conclusion. However, according to the results of the linear regression analysis, none of the factors considered in this study had a statistically significant influence on the probability of developing an adverse reaction to vancomycin or linezolid.

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

Objective. To analyze spontaneous reports (SRs) from the Russian database of adverse reactions (Automated information system "Pharmacovigilance" of Roszdravnadzor), containing information on fatal outcomes during ceftriaxone treatment, and to identify factors associated with an increased risk of death with ceftriaxone use. Materials and Methods. The study included 122 SRs concerning fatal cases during ceftriaxone therapy. All SRs were submitted to the Russian pharmacovigilance database from 06 May 2019 to 23 November 2022. A retrospective analysis of fatal adverse reactions cases in ceftriaxone treatment was carried out according to the following parameters: gender, age, drug intake and route of administration, clinical symptoms of anaphylaxis. Additionally, indications for the simultaneous use of drugs for local anesthesia as a solvent were evaluated. Results. A total of 86 SRs (70.5%) were primary and relevant for further analysis. 16 SRs (18.6%) were registered in the database for 8 months of 2019, 25 (29.1%) – for 2020, 15 (17.4%) – for 2021, for less than 11 months 2022 received 30 reports (34.9%). The number of adverse reactions reports in male and female patients was similar. Among the age groups, the largest number of SRs was observed in middleaged and elderly patients – 27 (31.4%) and 23 (26.7%) reports, respectively, 8 cases (9.3%) were registered in pediatric population. The development of fatal adverse reactions in the hospital was reported in 50 (58.1%) SRs, in outpatient setting – in 31 (36.1%) SRs. 18 SRs were identified with an indication of the patient’s self-treatment, which is 20.9% of all primary reports. Clinical symptoms of anaphylactic shock were noted in 63 reports (73.3%). Additional analysis of the combined use of ceftriaxone and local anesthetics cases revealed a range of medical errors. Conclusions. Ceftriaxone treatment was associated with a high risk of anaphylactic shock. The use of this antibiotic in outpatient setting, especially as self-treatment is an additional risk factor for death. Inappropriate use of local anesthetics in combination with ceftriaxone is an additional serious risk factor for fatal outcome.

Pharmacovigilance studies based on spontaneous reporting systems use disproportionality analysis methods to identify drug‐event combinations with higher‐than‐expected reporting. Enhanced reporting is deemed as a proxy for a detected signal and is used to generate drug safety hypotheses, which can then be tested in pharmacoepidemiologic studies or randomized controlled trials. Higher‐than‐expected reporting means that the reporting rate of a drug‐event combination of interest is disproportionately higher than the rate in a specific comparator or reference set. Currently, it is unclear which comparator is the most appropriate for use in pharmacovigilance. Moreover, it is also unclear how the selection of a comparator may affect the directionality of the various reporting and other biases. This paper reviews commonly used comparators chosen for signal detection studies (active comparator, class‐exclusion comparator, and full data reference set). We give an overview of the advantages and disadvantages of each method based on examples from the literature. We also touch upon the challenges related to the derivation of general recommendations for the selection of comparators when mining spontaneous reports for pharmacovigilance. [ABSTRACT FROM AUTHOR]

Aims: Recent case reports have suggested that sodium‐glucose co‐transporter 2 (SGLT2) inhibitors may interact with statins to increase their risk of myotoxicity. We assessed the risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins. Methods: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2013 to 2021 for reports including SGLT2 inhibitors, statins or both. We estimated several measures of disproportionate reporting of myopathy and rhabdomyolysis associated with concomitant use of SGLT2 inhibitors and statins: reporting odds ratio (ROR) with 95% confidence interval (CI), Ω shrinkage measure (safety signal if >0) and an extension of the proportional reporting ratio (PRR) (two‐criteria set, safety signal if both criteria are met), using the full FAERS dataset as the reference set. In sensitivity analyses, we focussed on specific SGLT2 inhibitor‐statin pairs with higher interaction potential (canagliflozin‐rosuvastatin, empagliflozin‐rosuvastatin) and accounted for stimulated reporting. Results: There were 456 myopathy and 77 rhabdomyolysis reports involving both an SGLT2 inhibitor and a statin. Concomitant use of SGLT2 inhibitors and statins was not associated with an increased risk of myopathy (ROR 0.79, 95% CI 0.70 to 0.89) or rhabdomyolysis (ROR 0.58, 95% CI 0.41 to 0.83) reporting. For both outcomes, the Ω shrinkage measure was negative and only one criterion of the PRR extension was met. SGLT2 inhibitor‐statin pairs with higher interaction potential yielded potential signals for rhabdomyolysis; these signals disappeared after accounting for stimulated reporting. Conclusion: There was no increased risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins or for specific drug pairs. [ABSTRACT FROM AUTHOR]

Objective. To perform pharmacoepidemiological analysis of spontaneous reports of adverse drug reactions (ADRs) occurred during macrolide group antibiotics prescription and registered in the “Pharmacovigilance 2.0” subsystem of the Federal Service for Surveillance in Healthcare. Materials and Methods. A retrospective pharmacoepidemiological analysis of spontaneous reports of ADRs arising from the use of all macrolide and azalide antibiotics registered in Russia and registered in the electronic database of the “Pharmacovigilance 2.0” subsystem of the Federal Service for Surveillance in Healthcare for the period from 01.04.2019 to 30.11.2022 was performed. Results. Analysis of the number of spontaneous reports of ADRs, their structure, outcomes and severity criteria was performed. The most clinically significant ADRs were identified, the occurrence of which was reported to pharmacovigilance bodies. The results of a retrospective pharmacoepidemiological analysis showed that the development of complications of pharmacotherapy in most cases was associated with the use of azithromycin and clarithromycin. The main clinical manifestations of adverse drug reactions were skin and subcutaneous tissue disorders, gastrointestinal disorders, as well as general disorders and injection site reactions. Conclusions. It was found that the reported events generally corresponded to the general spectrum of ADRs typical for individual representatives of macrolide and azalide antibiotics.

The pharmacovigilance system aimed at ensuring the safety of medicines has been functioning in Russia since 1997. However, at the moment, an important part of this system, pharmacy organisations, is not sufficiently involved in pharmacovigilance activities. Pharmacy personnel may be not prepared to collect information on adverse reactions associated with the use of medicinal products and submit it to regulatory authorities. The reason is not only that their knowledge of pharmacovigilance is insufficient, but also that little attention is paid in the educational process to the development of dialectical thinking, which is necessary for successful problem-solving. The available literature does not cover the importance of dialectical thinking as a professional competency of a pharmacy employee sufficiently well.The aim of the study was to substantiate the need in the development of dialectical thinking in employees of pharmacy organisations in order to increase their participation in the pharmacovigilance system.Materials and methods: 166 employees of pharmacies in Kazan were surveyed on the implementation of pharmacovigilance in pharmacy organisations. The authors used Spearman’s rank correlation coefficient to assess the extent of association between the variables identified in the survey (pharmacy’s standing in the pharmacovigilance system, respondents’ competence in pharmacovigilance, their familiarity with pharmacovigilance documentation, adverse reaction reporting, and so forth).Results: the majority of respondents perceive the importance of pharmacies for the pharmacovigilance system as medium (46.99%) and low (17.47%); the same is true for the level of pharmacovigilance development in pharmacies (45.63 and 27.5% of the respondents respectively). According to the correlation analysis, pharmacy employees do not associate the level of pharmacovigilance development in their pharmacy with their competence, which is characteristic of a dialectical failure. Most respondents tend to exaggerate the role of executive authorities, medical organisations, and pharmaceutical companies in the pharmacovigilance system and underestimate the role of pharmacies and pharmacy staff (only 17.62% of the respondents assign this role to pharmacies), which may be the reason for failing to fulfil pharmacovigilance duties and passing the responsibility to other parties to the circulation of medicinal products.Conclusions: according to the consolidated results, pharmacy employees may not consider themselves to be leading implementers of legislative initiatives, causally related to the effectiveness of pharmacovigilance system as a whole. Consequently, there is a need to form dialectical thinking in pharmacy employees within the framework of educational programmes. It will contribute to the development of reflection on their efforts in ensuring the safety of medicines and increase the effectiveness of their participation in pharmacovigilance activities.

Most of the medicines used to treat the novel coronavirus infection (COVID-19) are either approved under an accelerated procedure or not approved for the indication. Consequently, their safety requires special attention.The aim of the study was to review methodological approaches to collecting data on the safety of medicines, using COVID-19 treatment regimens involving azithromycin as a case study.Materials and methods: PubMed® (MEDLINE), Scopus, eLIBRARY, and Cyberleninka databases were searched for publications on azithromycin as part of combination therapy for COVID-19 in 2020–2021. Search queries included names of the medicinal product or its pharmacotherapeutic group and words describing adverse drug reactions (ADRs) during treatment.Results: the analysis included 7 publications presenting the results of studies covering the use of azithromycin as part of COVID-19 combination therapy in more than 4000 patients. Most commonly, the patients receiving COVID-19 therapy including azithromycin developed cardiovascular ADRs (up to 30% of azithromycin prescription cases). In 3 of the analysed publications, safety information was collected through spontaneous reporting and active identification based on the findings of laboratory and instrumental investigations performed during the clinical studies; in other 3, only spontaneous reports were used; and in the last one, ADR database information was studied.Conclusion: currently, information on ADRs associated with the use of medicines is mainly gathered via spontaneous reporting. Direct sourcing of information on personal experiences with a certain product from patients, among other means through social media analysis, opens a promising direction towards the improvement of existing approaches to collecting safety data.

Purpose: Literature reports of adverse drug events can be replicated across multiple companies, resulting in extreme duplication (defined as a majority of reports being duplicates) in the FDA Adverse Event Reporting System (FAERS) database because they can escape legacy duplicate detection algorithms routinely deployed on that data source. Literature reference field, added to in 2014, could potentially be utilized to identify replicated reports. FAERS does not enforce adherence to the Vancouver referencing convention, thus the same article may be referenced differently leading to duplication. The objective of this analysis is to determine if variations of the same literature references observed in FAERS can be resolved with text normalization and fuzzy string matching. Methods: We normalized the literature references recorded in the FAERS database through the first quarter of 2021 with a rule‐based algorithm so that they better conform to the Vancouver convention. Levenshtein distance was then utilized to merge sufficiently similar normalized literature references together. Results: Normalization of literature references increases the percentage that can be parsed into author, title, and journal from 61.74% to 93.93%. We observe that about 98% of pairs within groups do have a Levenshtein similarity of the title above the threshold. The extreme duplication ranged from 66% to 87% with a median of 72% of reports being duplicates and often involved addictovigilance scenarios. Conclusions: We have shown that these normalized references can be merged via fuzzy string matching to improve enumeration of all the individual case safety reports that refer to the same article. Inclusion of the PubMed ID and adherence to the Vancouver convention could facilitate identification of duplicates in the FAERS dataset. Awareness of this phenomenon may improve disproportionality analysis, especially in areas such as addictovigilance. [ABSTRACT FROM AUTHOR]

High rates of adverse drug reactions (ADRs) associated with nonsteroidal anti-inflammatory drugs (NSAIDs), as well as their irrational and uncontrolled use for self-medication require continuous updating of information on safety profiles of these products.The aim of the study was to assess the reporting rate, frequency, and severity of ADRs to NSAIDs and paracetamol products, based on data from periodic safety update reports (PSURs) submitted to the autonomous non-profit organisation “National Pharmacovigilance Research Centre”.Materials and methods: the study covered 104 PSURs for NSAIDs and paracetamol products. Consumption levels were calculated in patient days (PTDs) and patient years (PTYs) for each international nonproprietary name (INN). The authors also analysed clinical manifestations and severity of ADRs.Results: the total number of PTDs and PTYs for all NSAIDs and paracetamol products, including combination medicines, was 1 963 750 485 PTDs or 5 380 138.3 PTYs, respectively. The PSURs reported 459 ADRs, of which 304 (66.2%) were serious ADRs (SADRs). The comparative analysis of ADR frequencies, expressed as the “ADR/PTY” ratio, for individual products, helped to identify INNs with the highest reporting rates.Conclusions: high ADR/PTY and SADR/PTY values indicating better ADR reporting for some INNs, were observed for piroxicam, paracetamol, dexketoprofen, and ketoprofen, while the lowest values were observed for the “acetyl salicylic acid+caffeine+paracetamol” combination, acetylsalicylic acid, and phenylbutazone. Thus, the comparison of ADR/PTY and SADR/PTY ratios can be recommended as an inclusive approach both for analysis of reporting trends for individual products and for comparison of reporting rates of different medicinal products.

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines' selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance. [ABSTRACT FROM AUTHOR]

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines’ selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance.

Abstract Background Comprehensive analysis of all available data in spontaneous reports (SRs) can reveal previously unidentified medication errors (MEs). Methods To detect MEs, we performed a retrospective analysis of SRs submitted to the Russian pharmacovigilance database in the period from January 01, 2012, to August 01, 2014. This study evaluated SRs of cases where beta-lactam antibiotics were the suspected drug. Results A total of 3608 SRs were analyzed. MEswere detected in 1043 reports (28.9% of all cases). The total number of detected errors was 1214. Reporters themselves indicated MEs in 29 SRs. A term denoting an ME was selected in the “Adverse Reactions” section in 18 of these SRs, whereas in the other 11 reports information on the ME was found only in the “Case narrative” section. MEs were associated with wrong indications in 32.5% of the cases; 61.0% of these cases were viral infections. Various dosing regimen violations constituted 29.7% of MEs. A contraindicated drug was administered in 17.3% of all detected MEs, most commonly to a patient with a history of allergy to the suspected drug or severe hypersensitivity reactions to other drugs of the same group. Conclusion Automatic identification of MEs in the pharmacovigilance database is sometimes precluded by the absence of a code for the respective episode in the “Adverse Reactions” section, even when the error was detected by the reporter. The most frequent types of MEs associated with the use of beta-lactams in Russia are the leading risk factors of growing bacterial resistance.

Abstract Background There are no reports on investigations of the characteristics of adverse drug reaction (ADR) reports for pediatric patients in the Japanese Adverse Drug Event Report database (JADER) and the utility of database for drug safety surveillance in these patients. Method We aimed to evaluate ADR reports for pediatric patients in the JADER. We used spontaneous ADR reports included in the JADER since April 1, 2004, to December 31, 2017, which was downloaded in April 2018. In a total of 504,407 ADR reports, the number of spontaneous reports was 386,400 (76.6%), in which 37,534 (7.4%) were unknown age reports. After extraction of 27,800 ADR reports for children aged

The authors conducted a retrospective analysis of Russian database of spontaneous reports (SRs) for the period from 01.01.2012 to 01.08.2014. They analyzed 3608 SRs concerning adverse drug reactions associated with beta-lactam antibiotics to identify medication errors (MEs). MEs were detected in 1043 (28.9%) SRs, total amount of MEs was 1214. Medication error-related terms were indicated by reporters in 29 (0.8%) SRs. The most common types of identified MEs were inappropriate indication for the antibiotic - 32.5% MEs, deviations from the recommended dosing scheme - 29.7% MEs, and the use of contraindicated drug - 17.3% MEs. The use of antibiotics for viral infections and errors associated with a patient with documented hypersensitivity to administered drug pose a special problem. The highest number of SRs with MEs was associated with the use of cefazolin (50.8% SRs), amoxicillin (40.9% SRs), amoxicillin/clavulanate (40.0% SRs). The study shows the need to develop measures for prevention of MEs associated with the use of beta-lactam antibiotics in clinical practice.

Abstract Background Older adults are more prone to develop adverse drug reactions (ADRs) since they exhibit numerous risk factors. The first aim was to analyse the number of spontaneous ADR reports regarding older adults (> 65) in the ADR database of the German Federal Institute for Drugs and Medical Devices (BfArM) and to set them in relation to i) the number of ADR reports concerning younger adults (19–65), and ii) the number of inhabitants and assumed drug-exposed inhabitants. The second aim was to analyse, if reported characteristics occurred more often in older vs. younger adults. Methods All spontaneous ADR reports involving older or younger adults within the period 01/01/2000–10/31/2017 were identified in the ADR database. Ratios concerning the number of ADR reports/number of inhabitants and ADR reports/drug-exposed inhabitants were calculated. The reports for older (n = 69,914) and younger adults (n = 111,463) were compared using descriptive and inferential statistics. Results The absolute number of ADR reports involving older adults increased from 1615 (2000) up to 5367 ADR reports (2016). The age groups 76–84 and 70–79 had the highest number of ADR reports with 25 ADR reports per 100,000 inhabitants and 27 ADR reports per 100,000 assumed drug-exposed inhabitants. For both ratios, the number of reports was higher for males (26 and 28 ADR reports) than for females (24 and 26 ADR reports). Fatal outcome was reported almost three times more often in older vs. younger adults. Six out of ten drug substances most frequently suspected were antithrombotics (vs. 1/10 in younger adults). For some drug substances (e.g. rivaroxaban) the ADRs reported most frequently differed between older (epistaxis) and younger adults (menorrhagia). Conclusions There is a need to further investigate ADRs in older adults since they occurred more frequently in older vs. younger adults and will likely increase in future. Physicians should be aware of different ADRs being attributed to the same drug substances which may be more prominent in older adults. Regular monitoring of older adults taking antithrombotics is recommended.

Abstract Background Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). Methods We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. Results The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8). Conclusions The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

INTRODUCTION. Newly identified risks associated with the use of fluoroquinolones and the spread of antimicrobial resistance make the identification and analysis of medication errors (MEs) in prescribing fluoroquinolones especially important for providing rational antibiotic therapy. Fluoroquinolones that are most commonly used in real-world clinical settings include levofloxacin.AIM. This study aimed to examine the pattern of MEs associated with fluoroquinolones, exemplified by levofloxacin, through an analysis of spontaneous reports (SRs) submitted to the Russian pharmacovigilance database.MATERIALS AND METHODS. The authors retrospectively analysed the SRs of adverse drug reactions (ADRs) submitted to the Russian pharmacovigilance database between 1 April 2019 and 28 February 2023. According to the selected inclusion criteria, the study focused on the SRs that specified levofloxacin as a suspect medicinal product and described ADRs that took place in the Russian Federation. ME identification used summaries of product characteristics for levofloxacin approved in Russia, official clinical guidelines, and the antimicrobial stewardship guidelines Strategy for the Control of Antimicrobial Therapy (SCAT).RESULTS. The analysis included 950 SRs. MEs were identified in 307 (32.3%) of these SRs, and the total number of MEs was 332. MEs associated with the selection of the medicinal product included prescribing levofloxacin to patients without an indication for antibacterial therapy (38.9%, n=129, with 76.0% of cases being viral infections), incorrect selection of levofloxacin as a first-line antibacterial agent (18.1%, n=60), and irrational and excessive prescribing of levofloxacin in combination with other antibacterial agents (15.4%, n=51). Less frequently identified MEs were related to inappropriate dosing (13.0%, n=43), levofloxacin use in patients with contraindications (8.7%, n=29), and incorrect selection of the route of administration (3.9%, n=13) and the dosage form (2.1%, n=7).CONCLUSIONS. According to the results of this study, the practice of prescribing antibacterial agents for viral infections persists despite strong evidence of ineffectiveness in such cases. Antibacterial agents can be used effectively and safely only if prescribed for approved indications, administered at recommended doses, and delivered via specified routes of administration. The overuse of antibiotics may have negative sequelae not only for the health of an individual patient but for the health of the general population because of the increased risk of antimicrobial resistance. Therefore, there is a need to develop measures to limit the excessive use of antibiotics.

INTRODUCTION. With the development of the Internet and the increasing availability of social networks and fora, patients have received an opportunity to share their medication experiences online. According to the guidelines on Good Pharmacovigilance Practices, social media can be considered an important additional source of patient-derived information in post-marketing surveillance, but the effectiveness of their use in detecting adverse drug reactions (ADRs) is still being investigated.AIM. This study aimed to analyse the results of relevant original studies and assess the potential of using social networks and online patient fora as a source of information on ADRs associated with the use of medicinal products.DISCUSSION. Published studies indicate that posts on social networks and patient fora describe both minor and serious ADRs, including new ADRs. The relevance of social media as a source of information about the safety of a medicinal product varies depending on several factors, including the medicinal product class and time on the market, as well as the platform demographics. Young users (18–44 years) are interested in online discussions about medicinal products for mental and reproductive system disorders. Users aged 45–64 years tend to discuss the use of medicinal products for chronic pain (including muscle pain), menopause, and gastritis. Discussions among users over 65 years old predominantly focus on medicinal products for diabetes, heart conditions, and muscle pain. People are much more likely to describe ADRs associated with the use of medicinal products for orphan diseases and cancer on fora for patients than on social networks in general, and vice versa for ADRs associated with the use of medicinal products for mental disorders. In addition, social media may be of interest as a source of information about cases of overdose, misuse and off-label use of medicinal products, and use of medicinal products during pregnancy and lactation.CONCLUSIONS. Social media can be a source of valuable information about the safety of medicinal products and the impact of ADRs on the quality of patients’ lives. Marketing authorisation holders can obtain new information about the safety of medicinal products by extending their safety monitoring strategies to include social media. Nevertheless, since the relevance of a particular social network or patient forum for the detection of ADR cases varies considerably, a preliminary assessment is necessary to ascertain the presence of information on the medicinal product of interest.

Purpose: This study aimed to identify factors that influence the decision to take safety regulatory actions in routine signal management based on spontaneous reports. For this purpose, we analyzed the safety signals identified from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and related information. Method: From the signals that the FDA identified in the FAERS between 2008 1Q and 2014 4Q, we selected 216 signals for which regulatory action was or was not taken. Characteristics of the signals were extracted from the FAERS quarterly reports that give information about what signals were identified from the FAERS and what actions were taken for them, and the FAERS data released in the same quarter when the signal was published. Univariate and multivariable logistic regression analysis was used to assess the relationship between the characteristics of each of the signals and the decision on regulatory action. Result: As a result of the univariate logistic regression analysis, we selected 5 factors (positive rechallenge, number of cases accumulated in the last one-year period before the signal indication, previous awareness, serious outcome, risk for special populations) to include in the multivariable logistic regression model (p < 0.2). The multivariate logistic regression analysis showed that the number of cases accumulated in the last one-year period before the signal indication and previous awareness were associated with the regulatory action (p < 0.05). Conclusion: The present study showed that number of cases accumulated in the last one-year period before the signal indication and previous awareness potentially associated with the United States regulatory action. When assessing safety signals, we should be careful of the adverse events with a large number of cases accumulated rapidly in a short period. In addition, we should pay attention to new information on not only unknown risks but also previously identified and potential risks. [ABSTRACT FROM AUTHOR]

Herbal tonic and adaptogens are often used to improve overall well-being. However, few clinical evidence supports their use and their safety is not known before marketing. In this context, the aim of our study was to analyze the spontaneous reports of suspected adverse reactions (ARs) to performance enhancing herbal dietary supplements collected by the Italian Phytovigilance System. Between March 2002 and September 2020, 110 spontaneous reports were collected, 58 of which related to products containing botanicals, alone or in association. Twenty-three serious reactions were reported, 21 of which required hospitalization, one was life-threatening and another caused disability. Dermatological and cardiovascular reactions were the most frequent. Hepatic ARs were the most serious (9 out of 10). A positive dechallenge was indicated in 69% of cases, while a positive rechallenge occurred in 15%. Concomitant use of other products was present in 18 reports (31%), while predisposing conditions were indicated in 17 (29%). Present data highlight safety concerns on herbal dietary supplements used as cognitive and physical performance enhancers, mainly due to their quality and use without expert supervision. Considering that postmarketing surveillance is not required for these products, spontaneous reports represent the only tool to point out risks related to food supplements. [ABSTRACT FROM AUTHOR]

What is known and objective: The use of glucagon‐like peptide‐1 (GLP‐1) analogues has been linked to the risk of thyroid cancer. Spontaneous reports can provide information about rare adverse events occurring after the time of marketing. Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of thyroid cancer during GLP‐1 analogues treatment in patients with diabetes. Methods: Herein, we analysed all reports of thyroid cancer reported with GLP‐1 analogues in EudraVigilance database from their first marketing authorization till 30 January 2020. A case/non‐case method was used to assess the association between thyroid cancer and GLP‐1 analogues, calculating proportional reporting ratios (PRRs) and their 95% confidence interval (CI) as a measure of disproportionality. The cases were identified with Medical Dictionary for Regulatory Activities (MedDRA) version 22.1. Results and discussion: There were 11 243 cases of thyroid cancer and related preferred terms (PTs) in the 6 665 794 reports recorded in EudraVigilance during the study period. GLP‐1 analogues were involved in 236 cases. Exenatide, liraglutide and dulaglutide met the criteria to generate a safety signal, suggesting that thyroid cancer is reported relatively more frequently in association with these drugs than with other medicinal products. The association was strongest for liraglutide followed by exenatide with PRR of 27.5 (95% CI, 22.7‐33.3) and 22.5 (95% CI, 17.9‐28.3), respectively. Disproportionality was also observed for GLP‐1 analogues and individual identified preferred term, that is thyroid cancer (N = 111), medullary thyroid cancer (N = 64) and thyroid neoplasm (N = 46) with PRR of 14.4 (95% CI, 11.8‐17.4), 221.5 (95% CI, 155.7‐315.1) and 35.5 (95% CI, 25.9‐48.5), respectively. What is new and conclusions: Our findings showed disproportionality for thyroid cancer, medullary thyroid cancer and thyroid neoplasm in patients treated with GLP‐1 analogues. We have found evidence from spontaneous reports that GLP‐1 analogues are associated with thyroid cancer in patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population., Methods: We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20-64 years) using disproportionality analysis., Results: We found a significant association between severe ADEs of cardiac and renal/urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults., Conclusion: The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Children are more exposed to inappropriate medicine use and its consequent harms. Spontaneous reporting of suspected Serious Adverse Drug Reactions (SADR) increases knowledge and prevention of pharmacotherapy risk. Disproportionality measures are useful to quantify unexpected safety issues associated with a given drug-event pair (signals of disproportionality). This cross-sectional study aimed to assess SADR reporting and safety signals for Brazilian children from 0-12 years old, notified between January 2008 and December 2013 from the Brazilian Surveillance Agency (Notivisa). Information from serious reports (gender and age of the patient, event description, suspected drug) was included. Disproportionality analysis based on Reporting Odds Ratios with a confidence interval of 95% was conducted to identify possible signals of disproportionate reporting (SDR). Almost 30% of 1,977 suspected SADR was related to babies (0-1-year-old). 69% of reports happened with intravenous dosage forms, and 35% of suspected SADR involved off label use according to age. Laronidase, miglustat, imipenem/cilastatin, and clofarabine were involved in six or more suspected deaths among 75 deaths reported. There were 107 SDRs, of which 16 events (15%) were not described in the product labels. There was a relatively higher number of SADRs in Brazilian children compared with studies from other countries. SDRs found, (especially drug-event pairs ‘imipenen/cilastatin–pneumonia’ and ‘laronidase–respiratory insufficiency’) should be investigated more. The reports of SADR with IV dosage forms and OL drug use suggest the need for drug research and the use of better dosage forms for children in Brazil.

The pharmacovigilance system currently represents as a complex of interstate, state, departmental and public institutions. This system provides the receipt and processing of information about facts and circumstances that pose a threat to life or health for person who using drugs at all stages of life cycle of drugs. In addition, in the framework of pharmacovigilance activities, a continuous evaluation benefit and risk of the use of registered and developed drugs. On the way to its formation, the Russian pharmacovigilance system is face a challenge with a spectrum of problems, including the fragmentation of the conclusions formulated and the identification of polymorphic "targets" for the subsequent appropriate managerial decisions at pharmacovigilance field. Classification of existing problems at the field of pharmacovigilance is the technique of integration variety of studied objects to several systematized groups for the subsequent high-level review of the way for optimization and the possibilities for increasing its effectiveness. The results of the studies using methods of content analysis of publications of pharmacovigilance, statistical analysis of spontaneous reports and a sociological survey made it possible to identify a number of problems in the Russian pharmacovigilance system that were grouped of five types: political, organizational, information, cultural and personal. These analyzes allow us to determine the way for further research of the possibilities for increasing the effectiveness of the pharmacovigilance system based on the integrated development of ways for optimize the activity of the leading pharmacovigilance subjects in five problem areas.

Purpose. The purpose of this study was to discover the prevalence and types of medication errors associated with the use of carbapenems. Materials and methods. We analyzed 161 spontaneous reports concerning adverse drug reactions associated with the carbapenems. All the reports were submitted to the Russian pharmacovigilance database between 01.01.2012 and 01.08.2014. Approved prescribing drug information, standards of medical care and practical guidelines for certain conditions were used to identify medication errors associated with specific products. Results. The prevalence of medication errors associated with the use of carbapenems was 24,8%. The reporters indicated medication error-related term only in 5,0% of these cases. The most common types of identified medication errors (44,0%) were deviations from the recommended dosing scheme, in most cases (20,0%) medication errors resulted from wrong frequency of administration of the antibiotic. Conclusions. The results of this study show that the reporters rarely recognize and identify medication errors. We suggest emphasizing the importance of compliance with the dosage regimen of antibiotics; the frequency of administration of carbapenems is critical.

Purpose. To study and compare the structure of off-label drug use in children in 2012 and 2015 by means of analysis of the national pharmacovigilance database. Materials and methods. We conducted a comparative analysis of 341 spontaneous reports about serious adverse reactions in children, submitted to the Russian pharmacovigilance database in 2012, and 467 suchlike spontaneous reports registered in 2015. Approved in the Russian Federation prescribing drug information was used to identify «off label» drug use. Results. It was established that 58,7% of suspected medicines in 2012 and 47,5% in 2015, the use of which was associated with the development of serious complications in pharmacotherapy in children, were prescribed with deviations from the recommendations of approved prescribing drug information. Systemic antimicrobial agents and drugs for the treatment of nervous system diseases were the most common groups of drugs prescribed off-label in pediatric practice. The main types of off-label violations were inappropriate indications, deviations from the recommended dosage regimen and the use of a drug in the age group of patients, wherein the drug has not been approved. Conclusion. Our research confirms, that the practice of off-label drug use in children is not safe. It is shown that spontaneous reporting is an effective method of study the problems of drug safety in children.

Purpose. To study the structure of serious adverse drug reactions and «off label» drug use in children by means of analysis of the national pharmacovigilance database. Materials and methods. We analyzed 341 spontaneous reports about serious adverse reactions in children, submitted to the Russian pharmacovigilance database in 2012, and 467 suchlike spontaneous reports registered in 2015. Results. Children of preschool age have higher risk of medical therapy complications. Most frequently, skin (33,4% in 2012 and 38,7% in 2015) and organism as a whole (21,4 and 21,1%, respectively) were involved in the pathological process. Antimicrobial drugs for systemic use (43,5% in 2012 and 43,8% in 2015) and drugs for nervous system (25,1 and 26,1% respectively) often caused them. Unexpected serious adverse reactions accounted for 16,9% of all complications in children in 2012, 10,8% in 2015. It was established that 58,7% of suspected medicines in 2012 and 47,5% in 2015, the use of which was associated with the development of serious complications in pharmacotherapy in children, were prescribed with deviations from the recommendations of approved prescribing drug information. The main types of «off-label» drug use were inappropriate indications, deviations from the recommended dosage regimen, the use of a drug in the age group of patients, wherein the drug has not been approved, and the use of a drug in the presence of contraindications to its use. Conclusion. Our research confirms that the practice of «off-label» drug use in children is an independent risk factor for developing adverse drug reactions. It is shown that the method of spontaneous reporting can help to identify the problems of drug safety and to develop recommendations for minimizing the risk of complications of pharmacotherapy in pediatric practice.

Problems of interchangeability of systemic interferons for treatment of multiple sclerosis are described. An analysis of 1,643 spontaneous reports existing in the Russian database for the period 2009 to 2015 was made in order to identify information on adverse reactions that occurred after replacement of systemically used interferons. Since 2010-2011 there have been reports on adverse reactions and lack of efficacy caused by the replacement of one systemic interferon for treatment of multiple sclerosis with another one with the same INN. Most of the reports indicated a «possible» degree of reliability of the cause-effect relationship. Most of the spontaneous reports of adverse reactions when replacing interferons beta-1a and beta-1b contained information about adult patients. More than half of the spontaneous reports of adverse reactions contained information on clinically signifiant events. When interferons beta-1a and beta-1b were replaced, there were mainly general disorders, reactions at the injection site, musculoskeletal disorders and neurologic disorders observed. The reference medication was well tolerated but replacing for a bioanalogous drug resulted in ineffectiveness or development of adverse reactions. The results of the study demonstrated that the data of spontaneous reports are important for making decision on the interchangeability of systemic interferons for the treatment of multiple sclerosis.

The article presents data obtained in a retrospective analysis of spontaneous messages (SM) on drug adverse reactions during pregnancy, recieved in the Russian base «Pharmacovigilance» AIS Roszdravnadzor, for the period 1 January 2015 to 31 December 2015 included.

We have prepared this review of the domestic and foreign scientific literature to characterize the different modern approaches to collecting of ADR information. Advent of new technologies in mobile devices and software applications is leading to facilitate information gathering. The importance of medical literature, social media and patient-generated data for pharmacovigilance were highlighted.

We have prepared this review of the domestic and foreign scientific literature on how to use the social media for pharmacovigilance purposes. We examined the complexities that are connected with this kind of monitoring and how to extract information on adverse drug reactions from the Internet. The importance of a systematic approach in assessing the safety of drugs and the benefits of social networks is underlined. A description of applications for smartphones, which allow you to easily and quickly report drug adverse reactions is provided.

The safety of application of different groups of antibacterial drugs in pediatrics among children is discussed in this article. The analysis was made of spontaneous reports in the national database for 2012, containing information about serious adverse reactions (AR) on antibiotics in the pediatric population. In addition to evaluating the overall structure of serious AR and their distribution to system organ classes, the role of different pharmaco-therapeutic groups of antibacterial drugs in the development of adverse effects of pharmacotherapy was analyzed. Particular attention was drawn to «off-label» prescriptions; their frequency and structures. It was shown that antibiotics are common cause of serious AR among children, and their use as «off-label» prescribed drugs is an additional risk factor for such reactions.

Pregnancy is characterized by overexertion of metabolism in the liver and some changes in metabolism, which can lead to various, including severe organ, damage. During pregnancy, according to international epidemiological studies, more than 80 % of women take medicines. Under polypragmasy it is extremely difficult to isolate a particular medicine responsible for the drug pathology in the liver in pregnant women. The article presents a retrospective analysis of spontaneous reports accepted from the Russian database of AIS Roszdravnadzor for the period from 01.01.2009 to 31.12.2016.

Background: Comprehensive analysis of all available data in spontaneous reports (SRs) can reveal previously unidentified medication errors (MEs). Methods: To detect MEs, we performed a retrospective analysis of SRs submitted to the Russian pharmacovigilance database in the period from January 01, 2012, to August 01, 2014. This study evaluated SRs of cases where beta-lactam antibiotics were the suspected drug. Results: A total of 3608 SRs were analyzed. MEswere detected in 1043 reports (28.9% of all cases). The total number of detected errors was 1214. Reporters themselves indicated MEs in 29 SRs. A term denoting an ME was selected in the "Adverse Reactions" section in 18 of these SRs, whereas in the other 11 reports information on the ME was found only in the "Case narrative" section. MEs were associated with wrong indications in 32.5% of the cases; 61.0% of these cases were viral infections. Various dosing regimen violations constituted 29.7% of MEs. A contraindicated drug was administered in 17.3% of all detected MEs, most commonly to a patient with a history of allergy to the suspected drug or severe hypersensitivity reactions to other drugs of the same group. Conclusion: Automatic identification of MEs in the pharmacovigilance database is sometimes precluded by the absence of a code for the respective episode in the "Adverse Reactions" section, even when the error was detected by the reporter. The most frequent types of MEs associated with the use of beta-lactams in Russia are the leading risk factors of growing bacterial resistance. [ABSTRACT FROM AUTHOR]

What is known and objective: Complementary and alternative medicine (CAM) is widely used worldwide for health maintenance, disease prevention and treatment. The objective of the study was to identify adverse drug reactions (ADR) associated with the use of CAM in Malaysia and factors which are associated with the more serious reactions. Methods: All ADR associated with the use of CAM products (including health supplements) submitted to the Malaysian Centre for ADR Monitoring, National Pharmaceutical Regulatory Agency over a 15‐year period were reviewed and analysed. Multivariate logistic regression analysis was performed to identify predictors of serious ADR. Results and discussion: From a total of 74 997 reports in the database, 930 (1.2%) involved CAM products, and 242 (26%) were serious with 36 deaths. About a third of the reports involved used CAM products for health maintenance. Most (78.1%) of the ADR reports implicated unregistered products with 16.7% confirmed to contain adulterants which were mainly dexamethasone. Of the 930 reports, the ADR involved skin and appendages disorders (18.4%) followed by liver and biliary system disorders (13.7%). The odds of someone experiencing serious ADR increased if the CAM products were used for chronic illnesses (odds ratio [OR] 1.99, confidence interval [CI] 1.46‐2.71), having concurrent diseases (OR 1.51, CI 1.04‐2.19) and taking concurrent drugs (OR 1.44, CI 1.03‐2.02). What is new and conclusions: The prevalence of serious ADR associated with CAM products is high. Factors identified with serious ADR included ethnicity, CAM users with pre‐existing diseases, use of CAM for chronic illnesses and concomitant use of CAM products with other drugs. The findings could be useful for planning strategies to institute measures to ensure safe use of CAM products. [ABSTRACT FROM AUTHOR]

Children are more exposed to inappropriate medicine use and its consequent harms. Spontaneous reporting of suspected Serious Adverse Drug Reactions (SADR) increases knowledge and prevention of pharmacotherapy risk. Disproportionality measures are useful to quantify unexpected safety issues associated with a given drug-event pair (signals of disproportionality). This cross-sectional study aimed to assess SADR reporting and safety signals for Brazilian children from 0-12 years old, notified between January 2008 and December 2013 from the Brazilian Surveillance Agency (Notivisa). Information from serious reports (gender and age of the patient, event description, suspected drug) was included. Disproportionality analysis based on Reporting Odds Ratios with a confidence interval of 95% was conducted to identify possible signals of disproportionate reporting (SDR). Almost 30% of 1,977 suspected SADR was related to babies (0-1-year-old). 69% of reports happened with intravenous dosage forms, and 35% of suspected SADR involved off label use according to age. Laronidase, miglustat, imipenem/cilastatin, and clofarabine were involved in six or more suspected deaths among 75 deaths reported. There were 107 SDRs, of which 16 events (15%) were not described in the product labels. There was a relatively higher number of SADRs in Brazilian children compared with studies from other countries. SDRs found, (especially drug-event pairs 'imipenen/cilastatin–pneumonia' and 'laronidase–respiratory insufficiency') should be investigated more. The reports of SADR with IV dosage forms and OL drug use suggest the need for drug research and the use of better dosage forms for children in Brazil. [ABSTRACT FROM AUTHOR]

Background: There are no reports on investigations of the characteristics of adverse drug reaction (ADR) reports for pediatric patients in the Japanese Adverse Drug Event Report database (JADER) and the utility of database for drug safety surveillance in these patients. Method: We aimed to evaluate ADR reports for pediatric patients in the JADER. We used spontaneous ADR reports included in the JADER since April 1, 2004, to December 31, 2017, which was downloaded in April 2018. In a total of 504,407 ADR reports, the number of spontaneous reports was 386,400 (76.6%), in which 37,534 (7.4%) were unknown age reports. After extraction of 27,800 ADR reports for children aged < 10 and 10–19 years, we excepted for ADR reports associated with a vaccine (n = 6355) and no-suspected drug reports (n = 86). A total of 21,359 (4.2%) reports were finally included in this analysis. Results: More than half of the ADR reports were for children aged < 10 years. Approximately 30% of ADR reports had multiple suspected drugs, which did not differ by age. The percentages of fatal outcomes of ADRs among patients aged < 10 and 10–19 years were 4.7 and 3.9%, respectively. The most frequently reported drug, reaction, and drug-reaction pair were oseltamivir, abnormal behavior, and oseltamivir and abnormal behavior, respectively. Conclusion: We clarified the characteristics of ADR reports for Japanese children by using the JADER. ADR report databases, especially those for pediatric patients, are valuable pharmacovigilance tools in Japan and other countries. Therefore, a proper understanding of the characteristics of the ADR reports in the JADER is important. Additionally, potential signals for ADRs in pediatric patients should be monitored continuously and carefully. [ABSTRACT FROM AUTHOR]

Purpose The collection and analysis of real‐world data for the active monitoring of medical device performance and safety has become increasingly important. Spontaneous reports, such as those in the Food & Drug Administration's (FDA's) Manufacturer and User Facility Device Experience (MAUDE), provide early warning of potential issues with marketed devices. This review synthesizes the current literature on medical device surveillance signal detection and provides a framework for application of methods to active surveillance of spontaneous reports. Methods: Ovid MEDLINE, Ovid Embase, Scopus, and PubMed databases were systematically searched up to January 2019. Additionally, five methods articles from pharmacovigilance were added that had potential applications to medical devices. Results: Among 105 articles included, the most common source of data (84%) was registries; median time between data collection and publication was 8 years. Surgical procedure outcome signal detection articles comprised 83% while 14% were on device outcome signal detection. The most common family of methods cited (70%) was Sequential Probability Ratio. Conclusion: Application of any signal detection algorithm requires careful consideration of influential factors, data limitations, and algorithmic assumptions. We recommend approaches using disproportionality, statistical process control, and sequential probability tests and provide R packages to further development efforts. The small number of published examples suggest that further development of statistical methods and technological solutions to analyze large amounts of data for device safety and performance is needed. Fundamental differences in products, data infrastructure, and the regulatory landscape suggest that medical device vigilance requires its own body of research distinct from pharmacovigilance. [ABSTRACT FROM AUTHOR]

Purpose Recent safety issues involving medical devices have highlighted the need for better postmarket surveillance (PMS) evaluation. This article aims to describe and to assess the quality of the PMS data for a medical device and, finally, to provide recommendations to improve the data gathering process. Methods: A descriptive analysis of medical device reports (MDRs) on the use of MRA, a specific type of hip implant replacement submitted to the Food and Drug Administration Manufacturer and User Facility Device Experience database from 1 January 2008 to 31 December 2017. The number of reports was described as the number of MDRs per unique MDR number and stratified by different variables. The quality was assessed by the level of completeness of the collected PMS data. Results: The total number of reports related to MRA was 2377, and the number of MDRs per year ranged between 84 in 2009 and 452 in 2017. Most of the reports were reported by manufacturer Depuy Johnson & Johnson and were reported by a physician. In 44.9% of the reports, the device problem was reported as "Unknown." When the device problem was known, in the majority of cases, it was related to an implant fracture. The quality of the collected data was assessed as low due to missing information. Conclusion: The underlying data should meet high quality standards to generate more evidence and to ensure a timely signal generation. This case study shows that the completeness and quality of the MDRs can be improved. The authors propose the development of tools to ensure a more dynamic complaint data collection to contribute to this enhancement. [ABSTRACT FROM AUTHOR]

Background: Older adults are more prone to develop adverse drug reactions (ADRs) since they exhibit numerous risk factors. The first aim was to analyse the number of spontaneous ADR reports regarding older adults (> 65) in the ADR database of the German Federal Institute for Drugs and Medical Devices (BfArM) and to set them in relation to i) the number of ADR reports concerning younger adults (19–65), and ii) the number of inhabitants and assumed drug-exposed inhabitants. The second aim was to analyse, if reported characteristics occurred more often in older vs. younger adults. Methods: All spontaneous ADR reports involving older or younger adults within the period 01/01/2000–10/31/2017 were identified in the ADR database. Ratios concerning the number of ADR reports/number of inhabitants and ADR reports/drug-exposed inhabitants were calculated. The reports for older (n = 69,914) and younger adults (n = 111,463) were compared using descriptive and inferential statistics. Results: The absolute number of ADR reports involving older adults increased from 1615 (2000) up to 5367 ADR reports (2016). The age groups 76–84 and 70–79 had the highest number of ADR reports with 25 ADR reports per 100,000 inhabitants and 27 ADR reports per 100,000 assumed drug-exposed inhabitants. For both ratios, the number of reports was higher for males (26 and 28 ADR reports) than for females (24 and 26 ADR reports). Fatal outcome was reported almost three times more often in older vs. younger adults. Six out of ten drug substances most frequently suspected were antithrombotics (vs. 1/10 in younger adults). For some drug substances (e.g. rivaroxaban) the ADRs reported most frequently differed between older (epistaxis) and younger adults (menorrhagia). Conclusions: There is a need to further investigate ADRs in older adults since they occurred more frequently in older vs. younger adults and will likely increase in future. Physicians should be aware of different ADRs being attributed to the same drug substances which may be more prominent in older adults. Regular monitoring of older adults taking antithrombotics is recommended. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). Methods: We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. Results: The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for 'general disorders and administration site conditions' from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for 'injury, poisoning, and procedural complications' from the class of single psychiatric medication (OR = 2.8). Conclusions: The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results. [ABSTRACT FROM AUTHOR]

Despite ongoing debates about its safety, the use of metamizole (dipyrone) is still increasing in many countries. In this study, we analysed spontaneous reports of suspected metamizole‐associated agranulocytosis recorded in EudraVigilance database from 1985 to 2017 with regard to patient and treatment characteristics as well as fatal vs non‐fatal outcomes and compared these findings among countries. A total of 1448 reports from 31 different countries were included (Germany 42.0%; Spain 29.6%; Switzerland 13.1%; other countries 15.3%). Mean age of patients was 53.6 years (63.4% females). Differences among countries were observed, for example with respect to patient age, route of administration and daily doses. Overall, median time between starting metamizole and developing an agranulocytosis was 13 days with 34.7% of cases occurring up to 7 days. This time was much shorter in patients who had already received metamizole before (median: 6 vs 15 days). About 16% of cases ended fatally. Patients with fatal outcomes were older and more often had also received methotrexate compared to those with non‐fatal outcomes. When adjusting for age and sex in a multivariable logistic regression, methotrexate was associated with an increased risk of fatal outcomes (odds ratio: 5.18; 95% confidence interval: 3.06‐8.78). In conclusion, metamizole‐associated agranulocytosis is still a life‐threatening condition, especially in the elderly and those also receiving methotrexate. As agranulocytosis can develop weeks after last administration and independently of dose and duration of treatment, prescribers and patients should be aware of its signs and symptoms. [ABSTRACT FROM AUTHOR]

Purpose The main objective of this study was to analyze validated cases of drug‐induced anaphylactic reactions in children with regard to incriminated drugs, clinical characteristics, and associated factors. A further objective was to compare differences in incriminated drugs and characteristics between validated cases and a reference excluding anaphylactic reaction cases (basic dataset). Methods: Spontaneous reports of anaphylactic reactions in children (0‐17 years) registered between January 2000 to December 2016 were extracted from the adverse drug reaction database of the German Federal Institute for Drugs and Medical Devices. These reports were restricted to drugs for which at least four cases were found. After case validation, 159 reports remained (validated dataset) and were compared with the basic dataset (n = 12.168 reports) using inferential statistics. Results: Estimated yearly increase of reports (36.8 vs 0.1), most frequently incriminated drugs (antibiotics 30.2% vs 11%, analgesics/antipyretics 22.0% vs 5.6%; P values less than 0.001) and route of administration (38.4% vs 6.7%) differed between the validated dataset and the basic dataset. Validated cases differed in severity (higher with atracurium), reported symptoms (urticaria leading with analgesics), and associated factors (atopy/allergy rarely reported with antibiotics) depending on the incriminated drug class. In 13.8% (11.3% if excluding repeated readministration in one person) of the cases, the drug had not been tolerated before. Conclusions: A heterogeneous clinical phenotype with differences in associated factors was observed, suggesting different underlying mechanisms triggered by the different drug groups. Occurrence of serious drug‐induced anaphylactic reactions in children could be reduced by carefully considering patient history. [ABSTRACT FROM AUTHOR]

Objective. To determine the prevalence of medication errors associated with the use of penicillin-group antibiotics through analysis of national spontaneous reporting database. Materials and Methods. The study involved examination of 1123 spontaneous reports about adverse drug reactions related to penicillin-group antibiotics. All these reports were sent to Russian safety database in the period from 01.01.2012 till 01.08.2014. To identify cases of medication errors we used Russian drug labels, standards of medical care and practical guidelines for certain diseases. Results. Medication errors were detected for 36,9% of all spontaneous reports. In 17% of these cases two or more errors were made. One third (32.9%) of all medication errors included different deviations from the recommended dosage regimen. An indication was absent or inappropriate in 29,8% cases of incorrect use of antibiotics. 13.0% medication errors were associated with the cases where the antibacterial drug was prescribed to a patient, who had contraindications to it, in most cases (92%) — to a patient with hypersensitivity to penicillin or to other beta-lactams. The most commonly used drugs, amoxicillin and amoxicillin/clavulanic acid, have the highest prevalence of medication errors — 41% and 40% respectively. Conclusions. The results of this study demonstrate a high rate of medication errors associated with the use of penicillin-group antibiotics. A range of different measures are recommended for error reduction: to follow an appropriate dosage regimen, to avoid prescribing antibiotics for treatment of viral infections, to collect drug anamnesis accurately, considering cross-hypersensitivity reactions.

The paper discusses whether patients' spontaneous reporting on adverse drug reactions is appropriate and possible.