Herbal medicinal products (HMPs) are widely used in medical practice due to their availability, ease of use, and relatively safe pharmacological profile. However, medicinal plants are capable of accumulating heavy metals and arsenic which can have toxic effect on the human body when found in HMPs. The aim of the study was to summarise and analyse requirements of the Russian and foreign pharmacopoeias for the limits of heavy metals and arsenic in HMPs. National and regional pharmacopoeias have limits for the content of the major toxic elements (lead, cadmium, mercury, chromium, and arsenic) in HMPs. The study showed that the Indian and Japanese pharmacopoeias include only semi-quantitative methods for determination of heavy metals and arsenic, while the Russian and Chinese pharmacopoeias allow for the use of both quantitative and semi-quantitative methods. It was demonstrated that the limits for heavy metals and arsenic are the same for herbal substances and HMPs. The development of consistent approaches to determination of heavy metals and arsenic content, a systematic transition to quantitative methods of analysis, and establishment of individual limits for toxic elements in different HMP dosage forms, will make it possible to achieve the so-called consistent harmonisation, ensure reliable assessment of the content of heavy metals and arsenic, and minimize the risk of their entering human body with HMPs.

According to clinical studies, the use of fluoroquinolone antibacterial agents is associated with such rare, but serious adverse reactions as aortic injuries. The aim of the study was to analyse scientific literature data on the risk of aortic injury during fluoroquinolone treatment. The analytical review showed that the risk factors for fluoroquinolone-induced aortic injury are male gender, age over 45 years, underlying aortic disease, as well as smoking and associated atherosclerosis. Clinical and morphological forms of fluoroquinolone-associated aortic injuries include dilatation (aneurysm development), dissection, and rupture. The analysis of data on the association between aortic injuries and the use of most common fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) showed that development of aneurysm and dissection was most often observed for levofloxacin, and least often for ciprofloxacin. The mechanism of aortic injury is due to fluoroquinolone-mediated activation of matrix metalloproteinases which damage elastic components of vascular walls, as well as reduction in lysyl oxidase expression and collagen synthesis. The ability of fluoroquinolones to form complexes with magnesium ions reduces the availability of magnesium to the cell enzyme systems, which delays synthesis of extracellular matrix structural proteins, leads to metalloproteinase activation and calcification of the vascular walls. Prevention, early detection, and timely management of the above-mentioned issues depend on the awareness of different medical specialists about the risks of aortic injury associated with the use of fluoroquinolone antibiotics.

Good pharmacovigilance practices (GVP) of the Eurasian Economic Union (EAEU) were prepared based on the GVP of the European Medicines Agency that have been in force in the European Union (EU) since 2012. The EAEU GVP have been in force in the Russian Federation and the other EAEU member states since 2016. It is important to identify potential differences between the current regulations in order to harmonise requirements for the pharmacovigilance systems in the EU and EAEU. The aim of the study was to analyse and compare GVP requirements in the EU and EAEU. The analysis helped to identify differences in the structure and contents of GVP sections, the definitions of terms (EU GVP definitions are more detailed and supported by examples, subsections, and references to other documents). Moreover, supplements and annexes to the EU GVP contain figures, templates, examples, algorithms, and tables, which are missing in the EAEU GVP. Expert analysis of these differences as applied to assessment of the pharmacovigilance systems’ effectiveness, and practical activities of marketing authorisation holders, medicine developers, and regulatory authorities, demonstrated that the two GVPs are sufficiently harmonised and have very few differences. However, the number of differences between the documents increases, as changes are made to the EU GVP. A more comprehensive harmonisation of the EAEU GVP with the current version of the EU GVP will make it possible to develop and use uniform pharmacovigilance documents in the EU and EAEU, and will facilitate the introduction of EAEU medicines into the global pharmaceutical market.

Gender is an important factor affecting the risk of drug-induced adverse reactions in patients. According to scientific literature, the risk of drug-induced symptoms, syndromes, and diseases is 1.5–1.7 times higher in women than in men. The aim of the study was to analyse and systematise data on the factors responsible for increased risk of drug-induced diseases in women. It was demonstrated that the increased risk of complications in women following the use of certain pharmacological classes of drugs is associated with a combination of factors that affect pharmacokinetics and pharmacodynamics. These factors include anatomical and physiological characteristics, specificity of enzyme and transport protein activity/expression. Women, compared to men, have higher percentage of adipose tissue and lower percentage of water in the body, which affects the volume of distribution of lipophilic agents, such as opioids and benzodiazepines, resulting in their accumulation in the body. Women have a lower rate of renal excretion and elimination, as compared to men, which may lead to adverse reactions following the use of medicines with predominantly urinary excretion. Changes in the endocrine profile in women taking sex steroids as replacement therapy or a contraceptive measure, as well as fluctuations in endogenous sex steroids during the menstrual cycle, pregnancy, perimenopause, influence the volume of distribution, the activity of cytochrome P450 enzymes, and the glomerular filtration rate, and, thus, may affect the pharmacokinetics and pharmacodynamics of other medicinal products, which, in turn, affect the safety of pharmacotherapy. In order to increase the safety of pharmacotherapy in women, it is necessary to consider the revealed specific pharmacokinetic and pharmacodynamic parameters of the medicine in a given group of patients when selecting the treatment regimen, including the dosage regimen and routes of administration.

According to international epidemiological studies, about 80% of women have to use medicinal products during pregnancy, mainly during the first weeks of organogenesis in the case of an unplanned pregnancy, and for the treatment of chronic diseases or acute conditions developing during pregnancy. Specificity of pharmacokinetics and pharmacodynamics in pregnant women contributes to the development of adverse drug reactions (ADRs), many of which are serious and pose a threat to the life of the patient. The aim of the study was to retrospectively assess the frequency and development of ADRs in pregnant women living in the Republic of Crimea, based on the data in the regional safety database ARCADe (Adverse Reactions in Crimea, Autonomic Database). Materials and methods: the authors analysed spontaneous ADR reports registered in the ARCADe database from 1 January 2009 until 31 December 2018 for the category of patients described as “Pregnant women/childbirth”. Results: during the specified period, 268 ADR cases in pregnant women were added to the database. The most common reasons of ADRs in this category of patients were antibacterials for systemic use (130 cases, 48.5%), agents that have an effect on haematopoiesis and blood (54 cases, 20.15%), and agents that have an effect on the functions of the gastrointestinal tract (29 cases, 10.82%). The study of ADR clinical manifestations revealed a high incidence of local allergic reactions (140 cases, 52.2%), inhibition of haematopoiesis (60 cases, 22.4%), and dyspepsia (36 cases, 13.4%). The analysis of the severity of the registered ADRs demonstrated that in 15 cases (5.6%) the use of the prescribed medicinal product posed a threat to the patient’s life and required urgent pharmacotherapy and discontinuation of the suspected medicine, in 8 cases (3%) it resulted in hospitalisation or prolongation of hospital treatment, and in 3 cases (1.12%) it resulted in the temporary inability to work. Conclusions: the results of the study indicate the need for further retrospective and prospective studies aimed at analysing the safety of medicine use in pregnant women and assessing the risks of toxic effects on the foetus.

Analysis of administrative decisions of foreign regulatory authorities on the recall of medicines and/or the need for changes in the instructions for their medical use due to changes in the safety profile, conducted by experts of the Scientific Centre for Expert Evaluation of Medicinal Products revealed 19 administrative decisions. These decisions contained information on the following medicines registered in Russia: amikacin, tobramycin, gentamicin, neomycin, ciprofloxacin, delafloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, rufloxacin, сeftriaxone, ceftaroline, rifapentine, tigecycline, bacitracin, ertapenem, daptomycin, erythromycin, fosfomycin, ampicillin+sulbactam, chloroquine, hydroxychloroquine.