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.

Monitoring of information on the safety and efficacy of medicinal products that involves searching for data on benefits and risks of the post-approval use of medicinal products is one of the most important pharmacovigilance processes. The aim of the study was to summarise instruments and recommendations for effective monitoring of information on the safety and efficacy of medicinal products. The article presents the results of the analysis of the regulatory framework and modern tools for scientific literature and Internet information monitoring as part of routine pharmacovigilance. The main resources recommended for information monitoring are open-source scientific and medical bibliographic databases; scientific journals; websites of regulatory authorities and international organisations that monitor the efficacy and safety of medicines; social networks; and online patient communities. Drawing upon current regulatory documents and international good pharmacovigilance practices, the article presents recommendations on the number of resources needed for conducting qualitative monitoring and on the formulation and revision of a search strategy. It describes modern technological solutions in the field of information monitoring, substantiating the suitability of new achievements in such areas as Data Science and natural language processing (NLP) for marketing authorisation holders to collect and analyse data on the safety and efficacy of medicinal products. Regular updates of the search strategy and information channels, the use of software products for the automatic collection and analysis of data from various sources, and the creation of a continuous training system for pharmacovigilance specialists will allow for high-quality monitoring of information on the safety and efficacy of medicines.

Emergent ways to obtain information on the safety of medicinal products give relevance to the implementation of new information technologies into big data analysis in pharmacovigilance.
The aim of the study was to systematise data on the use of information technologies for pharmacovigilance process automation and identify problems and limitations that may arise when introducing the technologies.
Materials and Methods: the authors analysed literature on the subject matter and the practical experience of Flex Databases with the development of the electronic system for pharmacovigilance data processing designed for marketing authorisation holders.
Results: using the electronic pharmacovigilance system by Flex Databases as an example, the authors demonstrated the feasibility of basic, robotic, and cognitive automation and artificial intelligence technologies for data processing. Automation technologies allow the users to streamline information entry, process and analyse data, create reports and metrics, timely submit the reports and metrics to regulatory authorities, and manage risks and safety signals; they also help specialists in decision making. Artificial intelligence technologies (a wide range of technologies including machine learning, neural networks, and automatic natural language processing) are used to collect safety reports, amongst other things, through real-world clinical data analysis; prepare summary reports; and manage risks and safety signals. Moreover, human involvement is necessary only at certain stages, particularly to process the data on exceptional cases and to analyse the results in an expert capacity.
Conclusions: there is demand for process automation and artificial intelligence technologies at all stages of collection and analysis of pharmacovigilance information, from receiving a safety report to submitting it to regulatory authorities and identifying a safety signal. The deployment of the technologies within pharmacovigilance systems helps to increase the amount of data processed, among other things as a result of the inclusion of real-world clinical data into the search process. As the technologies reduce the degree of human involvement into routine processes of data collection, entry, verification, and analysis, the likelihood of errors reduces as well, whereas the quality and accuracy of the obtained results improve.

In the Russian Federation, a substantial proportion of the population (39.3–75.7%) opts for self-treatment. Self-administration of prescription medicinal products, particularly antibiotics, can lead to serious adverse drug reactions (ADRs). The safety of medicines in circulation relies upon the proper functioning of the pharmacovigilance system, both in general and in the case of self-medication ADRs.
The aim of the study was to analyse data on the serious ADRs attributed to self-treatment with antibiotics and reported to the Regional Centre for Drug Safety Monitoring of the Irkutsk Region, as well as on the pharmacovigilance problems associated with self-treatment.
Materials and methods: the study analysed the suspected ADR reporting forms from the database accumulated by the Regional Centre for Drug Safety Monitoring of the Irkutsk Region in 2011–2019. The inclusion criteria for the reporting forms were full completion and a Naranjo probability score categorising antibiotic–ADR causality at least as “possible”.
Results: of the total 2325 reports in the database, 790 (34%) were on the ADRs associated with the use of antibiotics. Of these, 222 reported serious ADRs caused by self-medication. The largest number of ADRs (126) was recorded in patients aged 40–70 years; the proportion of women (60.32%) was significantly higher than the proportion of men (39.68%). Hospitalisation was required for 23 patients with serious adverse events. In 80% of the studied cases, patients justified the need for self-prescription of antibiotics with cough (which they regarded as acute bronchitis), but their presumptive diagnosis coincided with that established in the hospital only in 47.83% of the cases. The reports of ADRs during self-treatment with antibiotics were mainly received from hospitals (205 cases), and much less often from outpatient clinics and directly from patients (9 and 8 cases, respectively). There were no reports from pharmacy organisations; and it may be assumed that their employees did not take active part in reporting.
Conclusions: the use of antibiotics for self-medication can lead to serious ADRs; therefore, the medicinal products of this class should be used only as directed by a doctor. To reduce the incidence of ADRs, it is necessary to raise awareness of the population and medical specialists conducting antibiotic therapy. The quality of medical care will benefit from proper performance of pharmacovigilance activities by all parties to the circulation of medicines, active involvement of patients in treatment safety monitoring, inclusion of specific sections on practical functioning of the pharmacovigilance system into the training curricula of pharmaceutical professionals, and creation of a feedback system connecting pharmacovigilance organisations to medical ones and other subjects of the circulation of medicines.

The main pharmacoepidemiological method for assessing the efficacy and safety of ongoing pharmacotherapy involves the collection of spontaneous reports on adverse drug reactions (ADRs) associated with the use of medicines.
The aim of the study was to analyse approaches to organising a system for collecting information on ADRs associated with the use of medicinal products, taking the Omsk region as a case study.
Materials and methods: the authors analysed 200 ADR reporting forms received by the Regional Centre for the Study of Side Effects of Drugs (RCSSED) in 2019.
Results: the analysis determined the ways of receiving the forms in the RCSSED. According to the analysis, the ADR reports were submitted by medical organisations in Omsk (86%) and the Omsk region (0.5%), as well as directly by patients (13.5%). The leading sources of reports were clinical pharmacologists (80% of the forms). Most of the reports were on ADRs associated with the use of psychotropic (41%) and antitumour (10%) medicinal products; it is explained by the proactive attitude and high commitment of medical personnel from the specialised clinics in Omsk towards their professional duties. Other important sources of reports in the Omsk region, which contributed to the number of spontaneous reports from patients, were the patient hotline and free consultation appointments with the clinical pharmacologist of the RCSSED on side effects of medicinal products. The article emphasises the leading role of the RCSSED clinical pharmacologist in educating medical personnel—in pharmacovigilance, collecting information about the development of ADRs, and the quality of reporting form filling—and coordinating the activities of the medical and pharmacy services, including the stages of laboratory assessment of medicinal product quality and pharmaceutical consultation of general public.
Conclusions: using the example of the Omsk region, the authors demonstrated the structural organisation of the collection of information about adverse reactions associated with the use of medicinal products. An important direction for further improvement of the organisation of ADR monitoring is the interaction with employees of pharmacy organisations, including additional training events for them.

Adverse drug reactions (ADRs) are recorded throughout the lifecycle of a medicinal product. In the post-marketing period, new ADRs are primarily identified via drug safety signals. In order to assess a signal and establish causality between an adverse drug reaction and a suspected medicinal product, it is necessary to evaluate the signal strength and quality.
The aim of the study was to analyse the information submitted to Russian regulatory authorities by a patient and check it for a potential causal association of acute tubulointerstitial nephritis (ATIN) with the use of ceftriaxone and with the patient’s principal diagnosis, Lyme disease.
Materials and methods: the authors analysed the patient’s submission received by the Ministry of Health of the Russian Federation in 2022 with a complaint that the treatment of Lyme disease with ceftriaxone had caused ATIN. The probability of a causal relationship between the medicinal product and the ADR was evaluated using the Naranjo algorithm.
Results: according to the review of literature and the spontaneous reports collected in Pharmacovigilance 2.0, the database in the Automated Information System of the Russian Federal Service for Surveillance in Healthcare, both ceftriaxone and the underlying condition (Lyme disease) may cause renal abnormalities. Ceftriaxone is potentially nephrotoxic; it mainly affects the tubular system of the kidneys. Borreliosis may cause kidney damage as well; such damage manifests clinically as rapidly progressing and fatal damage to the glomeruli.
Conclusions: the probability of a causal relationship between the development of ATIN in the complainant and the use of ceftriaxone was categorised as “possible”. However, the information available did not allow for establishing a definite relationship between kidney damage and the use of the medicinal product. Further monitoring of similar cases is necessary to minimise the risks of developing this pathology during treatment with ceftriaxone.

The overall incidence of healthcare-associated infections (HAIs) in patients with COVID-19 is lower than 15%. However, in critical COVID-19 patients, the incidence of HAIs may reach 50%, and the mortality rate may exceed 50%. This makes effective antibiotic therapy in this category of patients extremely important.
The aim of the study was to assess the rationality of antibiotic therapy in critically ill COVID-19 patients with HAIs, as well as analyse the timeliness and sufficiency of microbiological and laboratory diagnostic testing in these patients.
Materials and methods: the study comprised a retrospective analysis of medical records of the patients with COVID-19 complicated by HAIs who had been admitted to an intensive care unit of Moscow City Clinical Hospital 4 from 27.04.2020 to 01.11.2020. Antibacterial therapy was analysed in accordance with the principles set forth in the Strategy for the Control of Antimicrobial Therapy (antimicrobial stewardship) and the current Interim Guidelines on the Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19) of the Russian Ministry of Health. Statistical significance was evaluated using Student’s unpaired t-test. The qualitative comparison of independent groups was made using the χ2 test.
Results: HAIs developed in 138 (20.8%) of 664 patients admitted to the intensive care unit. The authors considered empirical antibiotic therapy irrational in 53.6% of these cases (74/138 patients) due to nonconformity to the current clinical recommendations. Empirical antimicrobial therapy was rational in 68.6% of survivors and 33.3% of non-survivors (p < 0.001). It was corrected based on the results of microbiological testing in 56.9% of survivors and 30.2% of non-survivors (p = 0.005). Procalcitonin levels, as a marker of bacterial infection, were determined in 74.5% survivors and 48.3% of non-survivors (p = 0.003).
Conclusions: Antibiotic therapy was rational in less than 50% of critically ill COVID-19 patients with HAIs. Having demonstrated a significant mortality decrease in the category of studied patients with rational antibiotic therapy, the study suggests that it is necessary to follow the current recommendations more carefully. The success of therapy also largely depends on its timely correction based on the results of HAI pathogen identification and other diagnostic measures, in particular, procalcitonin biomarker tests.

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.

Therapeutically, new oral anticoagulants (NOACs) are considered to be non-inferior or superior to vitamin K antagonists (warfarin). NOACs are included in current guidelines for the treatment of various cardiovascular diseases. Rivaroxaban medicinal products have been shown to effectively fight thrombotic complications of the new coronavirus infection, COVID-19. The wide clinical use of rivaroxaban products motivates the development of generics.
The aim of the study was to compare the pharmacokinetics and safety of rivaroxaban medicinal products in a single-dose bioequivalence study in healthy volunteers under fasting conditions.
Materials and methods: the bioequivalence study compared single-dose oral administration of Rivaroxaban, 10 mg film-coated tablets (NovaMedica Innotech LLC, Russia), and the reference product Xarelto®, 10 mg filmcoated tablets (Bayer AG, Germany), in healthy volunteers under fasting conditions. The open, randomised, crossover trial included 46 healthy volunteers. Each of the medicinal products (the test product and the reference product) was administered once; blood samples were collected during the 48 h after the administration. The washout between the study periods lasted 7 days. Rivaroxaban was quantified in plasma samples of the volunteers by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).
Results: no adverse events or serious adverse events were reported for the test and reference products during the study. The following pharmacokinetic parameters were obtained for Rivaroxaban and Xarelto®, respectively: C_max of 134.6 ± 58.0 ng/mL and 139.9 ± 49.3 ng/mL, AUC_0–48 of 949.7 ± 354.5 ng×h/mL and 967.6 ± 319.9 ng×h/mL, AUC _0–∞ of 986.9 ± 379.7 ng×h/mL and 1003.6 ± 320.4 ng×h/mL, T_1/2 of 8.2 ± 3.2 h and 7.8 ± 3.3 h. The 90% confidence intervals for the ratios of C_max, AUC_0–48, and AUC_0–∞ geometric means were 88.04–108.67%, 89.42–104.92% and 89.44–104.81%, respectively.
Conclusions: the test product Rivaroxaban and the reference product Xarelto® were found to have similar rivaroxaban pharmacokinetics and safety profiles. The study demonstrated bioequivalence of the medicinal products.

Nowadays, the problems caused by polypharmacy are recognised and widely discussed in the medical community. Multimorbidity, which is not uncommon in paediatric practice, comes with an increase in the number of prescriptions and necessitates an active search for tools to reduce the potential risk and frequency of adverse drug–drug interactions in paediatric patients.
The aim of the study was to use a clinical case to illustrate the need for monitoring, including laboratory monitoring of pharmacokinetic parameters, during concomitant therapy in paediatric practice.
Materials and methods: the study consisted in a retrospective analysis of the archived medical records of an 11-year-old child with nephrotic syndrome associated with a concomitant tuberculous process who had been receiving inpatient treatment with immunosuppressants at the Russian Children’s Clinical Hospital from May to July 2018.
Results: the prescription of cyclosporine for nephrotic syndrome entailed monitoring of plasma drug levels for potential pharmacokinetic interactions with the medicinal products used to treat the concomitant disease. The monitoring revealed an interaction between cyclosporine and rifampicin at the level of biotransformation. An adjustment of the concomitant therapy (discontinuation of rifampicin) allowed for achieving the target blood cyclosporine concentration, decreasing proteinuria and hypercholesterolemia, and increasing the blood total protein level in the child, which indicated the effectiveness of the ongoing treatment for the chief complaint.
Conclusions: the data obtained suggest that laboratory monitoring of pharmacokinetic parameters in paediatric polypharmacy can increase the effectiveness of therapy and prevent adverse reactions and irrational combination of medicinal products.

 This article is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews. Original publication: Ciapponi A, Fernandez Nievas SE, Seijo M, Rodríguez MB, Vietto V, García-Perdomo HA, et al. Reducing medication errors for adults in hospital settings. Cochrane Database of Systematic Reviews. Version published: 25 November 2021. https://doi.org/10.1002/14651858.CD009985