The processes of planning, performing, documenting, and follow-up of pharmacovigilance system inspections are regulated by the Good Pharmacovigilance Practices (GVP) and local regulations. These inspection processes apply mainly to marketing authorisation holders, developers of medicinal products for human use, and their authorised legal representatives, but they are presented from the perspective of regulatory authorities. Currently, there are no recommendations for pharmaceutical companies on how to prepare for a pharmacovigilance system inspection. The aim of the study was to develop recommendations on how pharmaceutical companies should prepare for a pharmacovigilance system inspection. The analysis of risks associated with scheduled and unscheduled inspections of pharmaceutical companies’ pharmacovigilance systems was performed with due consideration of the number of foreign marketing authorisations and the number of medicinal products under development according to the national registers of medicinal products and medical devices of the countries of the Eurasian Economic Union (EAEU), the Commonwealth of Independent States, and some European countries as of 30 June 2021. Some differences were identified in the work of Russian and foreign pharmacovigilance inspectorates, which are partially due to different numbers of EAEU-authorised medicinal products in the national markets. Based on the results obtained as well as personal experience as a pharmacovigilance officer in preparation of and participation in pharmacovigilance inspections of Russian companies by foreign regulators, implementation of corrective and preventive actions, the author of the paper has developed preliminary recommendations on how to prepare a EAEU pharmaceutical company’s pharmacovigilance system for an inspection. Effective management of pharmaceutical companies’ pharmacovigilance systems would contribute to the provision of the population with high-quality and safe medicines.

Drug-induced nephrotoxicity is the third most common cause of acute kidney injury (AKI). The aim of the study was to analyse and summarise data on the factors and mechanisms responsible for increased risk of drug-induced AKI, to analyse potential methods of its prevention and treatment. At present, the following phenotypes of drug-induced AKI are distinguished: acute vascular disease, acute glomerular disease, acute tubular injury / necrosis, and acute interstitial nephritis. It was discovered that most often these complications occur following the use of antimicrobial drugs, renin-angiotensin-aldosterone system inhibitors, non-steroidal anti-inflammatory drugs, and anticancer drugs, including targeted therapy. Risk factors for drug-induced AKI include age >65, female gender, low body weight, pre-existing chronic kidney disease, hypovolemia, hypoalbuminemia, acute and chronic heart failure, diabetes, malignancies, liver cirrhosis, prolonged use of nephrotoxic drugs, and simultaneous use of two or more nephrotoxic drugs. Discontinuation of the drug which resulted in kidney failure is the first and foremost principle for managing not only drug-induced, but all AKI patients. The use of potentially nephrotoxic drugs should be avoided, especially in high-risk patients, in order to prevent drug-induced AKI. If a patient needs a drug that affects renal hemodynamics, the therapy should begin with a minimum effective dose, and combinations of two and more nephrotoxic drugs should be avoided. Close monitoring of kidney function is crucial for high-risk patients. They should also be informed about the importance of adequate water consumption schedule for prevention of hypovolemia.

The frequency of adverse drug reactions (ADRs) in older patients is approximately 11.0%, according to scientific literature. Antibiotics are the third largest group (19.5%) of medicinal products in terms of ADR frequency in geriatric patients. Beta-lactam antibiotics are the empiric treatment of choice for older outpatients and inpatients with community-acquired pneumonia. The mortality in this group of patients accounts for 85% of the overall mortality from community-acquired pneumonia. The aim of the study was to analyse scientific data on risk factors and characteristics of adverse drug reactions associated with the use of beta-lactam antibiotics in older patients. Specificity of ADRs to beta-lactam antibiotics in this group of patients is due to age-related changes in pharmacokinetics and pharmacodynamics as well as polymorbidity and polypharmacy. The analysis of scientific literature demonstrated that there have not been so many pharmacoepidemiological studies in this group of patients, and their results have been inconsistent. The frequency, causes, and clinical manifestations of ADRs in geriatric patients are diverse and differ considerably from those in younger patients. Of the most widely used antibiotics, ceftriaxone and cefaclor exhibited a statistically lower risk of ADRs in older patients than in younger patients. At the same time, ceftriaxone was associated with a relatively higher frequency of serious ADRs in older patients as compared to younger patients, whereas the frequency of serious ADRs was lower with cefaclor. The likelihood of nephrotoxic, neurotoxic, and hepatotoxic ADRs associated with the use of beta-lactam antibiotics is becoming more and more obvious but it is still underestimated in clinical and geriatric practice. Safety monitoring, therapeutic drug monitoring with due consideration of ADR risk factors in older patients, and inclusion of older patients in clinical trials of antimicrobial drugs, would improve efficacy and safety of antibiotic treatment.

According to the World Health Organisation, pneumonia and other lower respiratory tract infections are one of the leading causes of death all over the world. Simultaneous treatment of pneumonia with antibacterial drugs and concomitant medicines may result in adverse drug reactions (ADRs). 

The aim of the study was to analyse ADRs resulting from drug-drug interactions in different empiric antibiotic treatment regimens used for mild community-acquired pneumonia (CAP), taking into account the concomitant symptomatic non-antibacterial treatment and chronic disease treatment. 

Materials and methods: the authors analysed spontaneous reports in the VigiBase global database (starting from the date the database was created and until 15 February 2021) on ADRs resulting from interactions of medicinal products included in the Russian clinical guidelines for CAP.

Results: the authors compiled a list of antibacterial drugs (amoxicillin+clavulanic acid, amoxicillin, ampicillin, azithromycin, clarithromycin, levofloxacin, moxifloxacin, cefotaxime, ceftriaxone, linezolid), as well as lists of medicinal products for symptomatic and concomitant treatment, based on the approved guidelines for management of CAP and frequent comorbid chronic diseases. They searched VigiBase for ADRs that may have resulted from drug-drug interactions involving these medicinal products. 

Conclusions: the analysis of adverse reactions used for mild CAP treatment demonstrated that the largest number of ADRs were associated with drug-drug interactions involving azithromycin, while the smallest number of ADRs were associated with cefotaxime and ceftriaxone. Further study of drug-drug interactions will help to prevent potential ADRs, identify rational drug combinations, and improve the existing patient management strategies.

A well-known problem in pharmacotherapy is an increased risk of adverse drug reactions (ADRs) in older as compared to younger patients. The Russian pharmacovigilance database includes a significant number of spontaneous reports of suspected ADRs in patients aged 65 and older. An increase in ADRs reporting makes it difficult to identify potential safety signals based on qualitative approaches only, which necessitates the use of statistical methods for signal detection based on disproportionality.

The aim of the study was to assess the applicability of quantitative methods for signal detection and analysis of ADR risks in the elderly using the Russian spontaneous report database.

Materials and methods: the study covered the reports on patients 65 years of age and older, which were submitted to the spontaneous report database from January 2008 until June 2018. The procedure recommended by the European Medicines Agency was used to identify potential statistical safety signals which were determined based on the following criteria: Reporting Odds Ratio, ROR—lower bound of the 95% confidence interval >1, number of cases ≥2; Proportional Reporting Ratio, PRR ≥ 2, Chi-square value χ2 ≥ 4, number of cases ≥3, lower bound of the 95% confidence interval >1, number of cases ≥3.

Results: 2231 potential statistical signals were identified. Of these, the vast majority of combinations of suspected drugs and ADRs were associated with known drug risks, and were not new safety signals for these drugs. The largest proportion of statistical signals was attributed to the following pharmacological groups: antiplatelet agents, cephalosporins, non-steroidal anti-inflammatory drugs, fluoroquinolones, angiotensin-converting enzyme inhibitors, metabolic agents, and indirect anticoagulants.

Conclusion: the results obtained indicate the applicability and effectiveness of statistical methods based on disproportionality of reporting for the analysis of the Russian spontaneous report database in order to identify potential drug safety issues.

Ensuring the safety of pharmacotherapy is a priority of the national regulatory health policy and is enshrined in the international and federal legislation. Survey of qualified pharmacovigilance experts on current problems in pharmacovigilance is one of the tools for improving the pharmacovigilance system efficiency.

The aim of the study was to analyse the Russian pharmacovigilance system organisation based on the results of a survey of pharmacovigilance officers.

Materials and methods: the authors carried out a survey of 26 pharmacovigilance officers from pharmaceutical companies.

Results: the majority of the respondents (50%) had short work experience in this area and combined pharmacovigilance duties with other functions in the company. At the same time, 73.08% of the respondents noted the lack of full-time pharmacovigilance staff in the company. According to the respondents, one of the most important problems in organising pharmacovigilance in the Russian Federation is a low level of staff qualification, which stems from the lack of specific pharmacovigilance courses at medical universities. The lack of qualified staff hinders the preparation of periodic and routine pharmacovigilance reports (according to 67.1% of the respondents) as well as the implementation of critical pharmacovigilance processes, e.g., risk management, and organisation of the pharmacovigilance quality management system. In addition, the paper discusses the issues of state support of private pharmacovigilance activities and the creation of a consolidated system for promoting consumer awareness about pharmacovigilance.

Conclusions: the improvement of the pharmacovigilance system should be based on: state oversight of the authorised regulatory and supervisory bodies, marketing authorisation holders, and professional communities; joint efforts on the part of professional communities and educational institutions in order to train staff in practical pharmacovigilance aspects—as part of post-graduate and professional education programmes; adequate reflection of pharmacovigilance problems and potential solutions in the mass media.