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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.

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.

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.

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 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.

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.

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.

The present study aimed to describe the trends and characteristics of adverse events following immunization (AEFI) reporting for children in the Japanese Adverse Drug Event Report database (JADER). We used 6280 AEFI reports for children aged Haemophilus influenzae type b conjugate vaccine and pyrexia among children aged

Classical methods used for signal detection in pharmacovigilance rely on disproportionality analysis of counts aggregating spontaneous reports of a given adverse drug reaction. In recent years, alternative methods have been proposed to analyze individual spontaneous reports such as penalized multiple logistic regression approaches. These approaches address some well-known biases resulting from disproportionality methods. However, while penalization accounts for computational constraints due to high-dimensional data, it raises the issue of determining the regularization parameter and eventually that of an error-controlling decision rule. We present a new automated signal detection strategy for pharmacovigilance systems, based on propensity scores (PS) in high dimension. PSs are increasingly used to assess a given association with high-dimensional observational healthcare databases in accounting for confusion bias. Our main aim was to develop a method having the same advantages as multiple regression approaches in dealing with bias, while relying on the statistical multiple comparison framework as regards decision thresholds, by considering false discovery rate (FDR)-based decision rules. We investigate four PS estimation methods in high dimension: a gradient tree boosting (GTB) algorithm from machine-learning and three variable selection algorithms. For each (drug, adverse event) pair, the PS is then applied as adjustment covariate or by using two kinds of weighting: inverse proportional treatment weighting and matching weights. The different versions of the new approach were compared to a univariate approach, which is a disproportionality method, and to two penalized multiple logistic regression approaches, directly applied on spontaneous reporting data. Performance was assessed through an empirical comparative study conducted on a reference signal set in the French national pharmacovigilance database (2000–2016) that was recently proposed for drug-induced liver injury. Multiple regression approaches performed better in detecting true positives and false positives. Nonetheless, the performances of the PS-based methods using matching weights was very similar to that of multiple regression and better than with the univariate approach. In addition to being able to control FDR statistical errors, the proposed PS-based strategy is an interesting alternative to multiple regression approaches.

The purpose of research is to assess adverse drug reactions, which were registered in Volgograd region, using spontaneous reports. Retrospectively notice cards of suspected adverse drug reactions received by the Volgograd regional center of drugs safety monitoring during 2010 and 2011 were analyzed. Evaluation of reliability of causal relationship «Drug— Adverse Drug Reaction» was carried out in accordance with Naranjo algorithm. In 2011 the volume of registered side effects grew almost 3 times by increasing the activity of doctors than in 2010. We defined the structure of drugs, which caused adverse reactions the most frequently. During these two years doctors rarely reported about adverse drug reactions of type A, so we can suppose that doctors had troubles with detecting causal relationship « Drug —Adverse Drug Reaction».