Registration and analysis of adverse events following immunisation (AEFIs) allow for objective assessment and systematisation of AEFI causes, and promotion of vaccination safety. Development of abscesses after DTP vaccination is a fairly common AEFI, however, they are not included in the “Side effects” part of the patient information leaflet of the vaccine. The aim of the study was to analyse reasons for abscess development after DTP vaccination and to elaborate recommendations on enhancing the vaccine safety. The review of literature data, solicited reports on AEFIs, and AEFI investigation reports submitted to the Scientific Centre for Expert Evaluation of Medicinal Products during 2014–2018 suggests that abscesses associated with DTP vaccination may be caused by the vaccine reactogenicity, quality defects arising during production or distribution, and vaccine administration errors by healthcare personnel. Lack of information in the documents submitted by medical institutions does not allow to rule out any of the identified reasons. The minimisation of risks of abscesses requires quality control of DTP vaccines, maintenance of the cold chain during transportation and storage, and compliance with aseptic regulations during administration. Additional pharmacovigilance measures will also help enhance vaccination safety: improvement and standardisation of data collection during investigation of abscess development in the post-vaccination period, obligatory inclusion of data on the thickness of children’s subcutaneous adipose tissue (weight, body mass index) and the length of the needle used for vaccination in AEFI investigation reports. It is advisable to add information on abscess risk in the “Side effects” part of the patient information leaflet of the DTP vaccine, and to update the “Dosage regimen and administration route” and “Precautions” parts in order to minimise the risk. Personnel of healthcare facilities performing vaccination should be made aware of the importance of providing detailed data on AEFIs for subsequent objective analysis.

Analysis of administrative decisions of foreign regulatory authorities on the recoil of medicines and/or the need for changes in the instructions for their medical use due to changes in the safety profi le, conducted by experts of the Scientifi c Centre for Expert Evaluation of Medicinal Products revealed 16 administrative decisions. These decisions contained information on the following medicines registered in Russia: norepinephrine, xylometazoline, mometason, liraglutide recombinant, exenatide, insulin recombinant human, insulin degludec, teriparatide, progesterone, gestodene, desogestrel, dienogest, drospirenone, norgestrel, lynestrenol, levonorgestrel, medroxyprogesterone, mestranol, nomegestrol, norethisterone, norgestimate, chlormadinone, cyproterone, estradiol, ethinylestradiol, etonogestrel, ethinylestradiol, fi nasteride, abiraterone, thiamazole, omega-3-acid ethyl esters, pitavastatin.

In 1968 the World Health Organisation initiated the development of an international programme for collection of data from the maximum number of sources about potential adverse effects of medicines. In order to implement this programme, a number of databases were created, such as the global database VigiBase, the European database EudraVigilance, and the database of the Eurasian Economic Union (EAEU). The aim of the present study was to compare approaches of the international spontaneous reports databases to collection, processing, and analysis of information on adverse drug reactions. It was demonstrated that the international databases VigiBase, EudraVigilance, and the EAEU database of adverse drug reactions contain different numbers of spontaneous reports, but serve the same objectives, namely to collect, process, and analyse information submitted as spontaneous reports. Unlike VigiBase that contains reports on authorised medicines coming from the national pharmacovigilance centres only, EudraVigilance also receives data from marketing authorisation holders and has reports on adverse drug reactions observed during clinical trials. The exchange of information between countries ensures rapid identification of safety signals concerning potential risks of medicines, and increases the likelihood of detecting rare and late-onset adverse reactions that may go unnoticed when analysing national data in a particular country. Spontaneous reports databases are an essential tool of the international drug safety monitoring community. Effective measures in this area will ultimately help to improve patients’ health and quality of life.

The safety of interferons was assessed by analyzing 499 spontaneous reports in the Russian database from 2015 to 2017. The results led to the conclusion that the safety profile of systemic interferon preparations that are widely used in medical practice to treat multiple sclerosis is defined by data in spontaneous reports for the development of adverse reactions to them or the ineffectiveness of using them.

Vaccine safety is an important aspect of mass immunization of the population. Adverse reactions that occur following vaccination result in a decrease in public confidence. The aim of this research was to identify information on the development of adverse events after immunization with vaccines included into the national vaccination calendars of the USA, European Union (EU), Japan, China, South Korea and India. Particular attention was paid to vaccines that are not included in the vaccination calendar, but are presented in the Russian Federation. During monitoring of vaccination against human papillomavirus information in the European Union, Japan and the United States, according the possible connection with development of autoimmune diseases was refuted. Monitoring of adverse events after vaccination with rotavirus vaccine I generation in the USA, EU and India, allowed to establish a link with the development of intestine invagination and limit the use of this medicinal product in favor of vaccine II generation. After starting vaccination against influenza was detected narcolepsy as a complication of this procedure; and when analyzing the complications of meningococcal vaccination Guillain — Barre syndrome was detected. We also analyzed information on various complications associated with vaccination against Japanese viral encephalitis, which was included into the national vaccination calendar of countries in Asia and the Pacifi c region — China, India, Japan, and South Korea. The main complications registered in the PRC after the introduction of Japanese encephalitis vaccine into the national vaccination calendar included: febrile seizures, thrombocytopenic purpura, encephalitis and meningitis. The main safety concerns about vaccines included into the national vaccination calendars of EU countries, the USA and the Asia-Pacific region concern vaccines that have recently appeared on the pharmaceutical market.

Due to repeated reports of adverse effects with the use of fluoroquinolone antibiotics, these drugs become over and over again the object of the close attention of pharmacovigilance specialists and health care specialists. The aim : to study the frequency and the nature of adverse reactions associated with the use of ciprofloxacin, based on the analysis of the spontaneous reports received by the Russian pharmacovigilance service. Materials and Methods : A retrospective analysis of the spontaneous reports of ciprofloxacin was conducted on the data-base «Pharmacovigilance» of the automated information system of Roszdravnadzor from 2008 to 2018. Results : 3403 adverse reactions that occurred in 2083 patients using ciprofloxacin were recorded. The most frequently developed reactions were from skin and subcutaneous tissues (37.3 %), general disorders and disorders at the injection site (21.1 %), gastrointestinal tract reactions (14.9 %). More than a one third of the reports contained information about serious adverse reactions. Unexpected reactions were identified as not recorded in the instructions for the medical use of ciprofloxacin: bradycardia, atrial arrhythmia, cyanosis, increased blood pressure. Conclusions : fluoroquinolone antibiotics with proven efficacy and years of experience in clinical use, continue to be drugs whose safety requires constant monitoring. The results of the study confirmed the possibility of detecting a wide range of the adverse reactions using the method of spontaneous reports. Regulatory authorities of the Russian Federation should recommend to registration certificate holders to include the information of adverse reactions of ciprofloxacin that were registered in the post-marketing period in the instructions for medical use.

In the 1960s, following the Thalidomide Disaster, the World Health Organization (WHO) initiated the development of an international drug safety monitoring programme. The objectives of this WHO programme are to improve the quality and safety of pharmaceuticals, and to support public health programmes by providing information for effective assessment of the risk-benefit ratio of medicinal products. The paper outlines the main focus areas of the programme and the mechanism of interaction between the countries involved. It summarises the functions of the WHO Collaborating Centre for International Drug Monitoring located in Uppsala, namely, accumulation and assessment of data on efficacy, inefficacy and risks of medicinal products, which are communicated by the participating countries, and provision of reliable and coherent data to specialists. The paper provides a review of online resources and methods used by VigiBase — global database of adverse drug reactions — that make it possible to search and analyse the data statistically. It describes the functions of the national monitoring centres located in different regions, and their interaction with the WHO. The dissemination of objective and reliable medical information throughout the world, promotion of pharmacovigilance as a science, creation of international partnerships and pooling of expertise from different countries allow for a significant improvement in the safety of pharmacotherapy.

Efficacy, safety and biotransformation features of any drug are fully revealed during widely using. Therefore, postmarketing studies of the pharmacological properties of drugs are an integral component of pharmacovigilance. The aim of this study was to evaluate the nature and frequency of drugs adverse reactions that have been reported in the post-marketing period, as well as a review of measures taken by foreign regulatory authorities to ensure the safety of use of these drugs. The results of monitoring the drug safety in the post-marketing period used in clinical practice during various time intervals are presented: from several years (atelizumab, daclizumab) to several decades (valproate, retinoids). The review included data from decisions of regulatory authorities, published in 2018. Recommendations from foreign sources on the rational use of drugs, ways to increase the benefit/risk ratio of adverse reactions when using drugs from different therapeutic groups and/or the need for changes in the instructions on their medical use due to changes in the safety profile are considered. These recommendations will be helpful to healthcare professionals, as well as persons authorized for pharmacovigilance by pharmaceutical companies. Particularly, this information may be of interest to rheumatologists, oncologists, neurologists, psychiatrists, as well as other physicians who use atezolizumab, tocilisumab, daclizumab, pomalidomide, valproate sodium and valproic acid, retinoids, clarithromycin, cotrimaxozol, cefalexine, hydroxycarbamide, ritonavir.

The monitoring of information on the safety of various drugs is becoming more relevant day by day, as the number of drugs on the pharmaceutical market increases, generic drugs, bio-analogous drugs appear. Long-term post-marketing use of a medicinal product allows to accumulate a sufficient evidence base and experience of application in various population groups, to study the features of the use of this drug. Information on the safe use of new drugs can be obtained in selected scientific publications. In addition to publications in the specialized scientific literature, regulators of different countries on the basis of new information give opinions on the need to make changes in instructions for medical use. When analyzing the recommendations of Russian and foreign regulatory authorities on restricting the circulation of medicines and / or the need to amend the instructions for their medical use in connection with the change in the assessment of the safety profile, we identified 16 administrative decisions of foreign regulatory bodies containing information about the following drugs registered in Russia. We consider all recommendations to be important information on the safety of medicines, which is addressed to specialists in the field of medicine, in particular to persons authorized by pharmacovigilance in pharmaceutical companies. In addition, this information may be of interest to physicians of various specialties who in their practice use buprenorphine, venlafaxine, gadolinium contrast drugs hydroxyethyl starch, daclizumab, duloxetine, denosumab, cladribine, clomifene citrate, milnacipran, methotrexate, pemetrexet, radium dichloride, rifampicin, phoebusostat, flupirtine.

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.

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.

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.

Apremilast is a new selective inhibitor of phosphodiesterase 4 (PDE4) of the class of small molecules, approved for treatment of psoriatic arthritis and psoriasis. The efficacy and safety of apremilast in the treatment of moderate to severe plaque psoriasis have been demonstrated in multicenter, randomized, double-blind, placebo-controlled clinical trials of ESTEEM 1 and ESTEEM 2 (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis). These studies describe adverse reactions such as mental disorders: depression, suicidal thoughts, suicidal behavior. However, data on the increase in the incidence of these adverse reactions during longer treatment with apremilast were not obtained. The article presents the reports from the UK regulator (MHRA) and international database VigiBase on the increased risk of developing suicidal thoughts, suicide attempts, completed suicides and suicidal behavior during treatment with apremilast.

Non-steroidal anti-inflammatory drugs (NSAIDs) are liders in selling both in the Russian Federation and worldwide. The combination of analgesic, anti-inflammatory and antipyretic effects make the drugs of this group very popular in patients with various diseases. The realization of NSAIDs in pharmacies occurs both by prescription and over-the-counter, so the safety assessment of the use of this group of drugs remains relevant. In the current practice, self-administration (responsible selfmedication) of drugs of the NSAID group is an additional factor affecting the safety of their intake. According to the studies, about 40 % of patients taking NSAIDs consider that NSAIDS are absolutely safe, and more than 30 % of those taking OTC NSAIDs use them in excess of the recommended dosages. We analyzed 3963 individual case safety reports (ICSR) in the federal database «Pharmacovigilance» from 07.12.2008 to 31.08.2017. The inclusion criterions was the presence of information on the off-label application of NSAIDs in the ICSR, reports of adverse effects that may be associated with the use of this drug or erroneous reports on the active substance, which was not present in this drug. The most frequent mistakes in the application were an increase of the daily dose, a change in the method of administration to patient who are contraindicated with this drug. There were 9 ICSR of burning sensation in the anus with the introduction of ibuprofen suppositories (not in the label), and 7 ICSR of ineffectiveness of the active substance, which was not present in this drug.

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.

The results of evaluating information in the Periodic safety update reports (PSUR) submitted by marketing-authorisation holder indicate a lack of understanding of regulatory requirements for the preparation of this document. As a result PSURs submitted by some marketing authorisation holders are returned to them for correction. The purpose of this article is to present the standard forms of PSUR, which will allow you to adequately prepare this reporting document.

The European Medical Agency (EMA) in 2012 formulated modern legislation defining the procedure for pharmacovigilance — the Good Pharmacovigilance Practices (GVP), which replaced the earlier provisions of the Pharmacovigilance Guidelines for Human Medicines. The signal management position is included in one of the GVP EMA modules and became part of the EAEC GVP Rules. EMA in 2017 published a regulatory guide for detecting a signal in spontaneous reporting databases, which became an Annex to Module IX of the GVP Rules «Signal Management». The approach proposed in the Appendix supplements the classical analysis of disproportionality with other data, based on both statistical and clinical judgments. The article deals with the problem of detecting signals about the safety of medicines. The main parameters that determine the effectiveness of methods for detecting signals on disproportionality and allowing to compare the productivity of different statistical methods with respect to each other are considered. Priority directions are considered when evaluating the signal, and key elements of a qualitative method for detecting signals are drawn up, taking into account the expert opinion.

Myopathy is a life-threatening disease that can be caused, among other things, by the intake of various medications. Despite the fact that many drug-induced myopathies are well known, however, many health professionals are not alert to myopathies caused by drug interactions. Myopathy is a wellknown adverse reaction of statins, and muscle damage can range from minor muscle pain and weakness to life-threatening rhabdomyolysis. Colchicine can also cause myopathy, including rhabdomyolysis. The combination of colchicine and statins can significantly increase the risk of myopathy compared with their intake separately. In cases of development of myopathy in patients receiving colchicine and statins simultaneously, the most common manifestation of drug interaction was muscle weakness, occurring in almost every case, and in some cases, muscle weakness was so severe that the patient lost the ability to move. In a third of cases, the development of muscle weakness was accompanied by muscular pain, and darkening of urine to tea shade. One study showed that 40 % of patients received concurrent combinations of drugs that increased the risk of muscle damage. It is concluded that the simultaneous administration of colchicine and statins requires an assessment of the “benefit-risk” ratio, as well as the administration of drugs in minimally effective doses.

Abstract. Detection and analysis of drug safety signals in children is a mandatory part of pharmacovigilance. The criteria for evaluating signals of adverse effects were considered. Spontaneous reports databases as a source for detecting signaling information about adverse reactions, including in children were used. More than 17.5 million cases of adverse reactions identified in WHO global database of individual case safety reports — VigiBase which was detected since 1968 in 120 countries — members of the WHO Drug Treatment Control Program. Of these, 1.5 million cases of adverse reactions occur in childhood. Objective: search and analysis for signal information in the post-marketing period of the use of drugs in children to increase the safety of pharmacotherapy in pediatric practice. Results: а causal relationship between desloratadine and weight gain was detected. Desloratadine is an active metabolite of loratadine so the researchers have considered reports on desloratadine and also on loratadine. In VigiBase there are reports of weight gain when taking desloratadine (44 messages) and loratadine (115 messages) in 2016. Among them, 22 reports on weight gain in children from 2 to 11 years. The Pharmacovigilance Risk Assessment Committee of the European Medical Agency (PRAC EMA) recommended marketing authorization holders to add an information about weight gain in children in prescribing information of drugs which contains desloratadine and loratadine. In September 2017, the Committee on Drugs for Human Use, following a review and analysis of VigiBase, approved the recommendations of PRAC EMA. Appropriate changes were made to the instructions for medical use for loratadine tablets. Conclusions. These results confirm the importance of long post-marketing studies, the results of which will provide significant assistance in improving the safety of pharmacotherapy in children.

Diabetes mellitus is the most acute medical and social problem related to the priorities of national health systems. The dramatic and urgent problems of diabetes mellitus are determined by the high prevalence of diabetes, high mortality and early disability of patients. The prevalence of diabetes mellitus in Western countries is 2–5 % of the population, and in developing countries reaches 10–15 %. Inhibitors of dipeptidylpeptidase-4 are one of the classes of drugs for the treatment of patients with diabetes mellitus type II. Now days the analysis of regulatory reports from developed countries show that the number of reports FDA, Health Canada on the risk of serious adverse reactions has increased. Not all detected adverse reactions are listed in the instructions for use among the possible side effects of the group of inhibitors of DPP-4. The article deals with reports of adverse reactions detected during the monitoring of databases of the Russian Federation and regulatory authorities of foreign countries. The safety research of the use of DPP-4 inhibitors is ongoing.