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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.

Some patients are more likely to have drug-induced diseases due to a number of risk factors, such as older age. The aim of the study was to analyse the effect of older age on pharmacokinetics and pharmacodynamics of medicines and the risk of developing drug-induced diseases. The analysis of scientific literature demonstrated that changes in the functions of body organs and systems caused by natural aging processes may potentially affect pharmacokinetics and pharmacodynamics of medicines and increase the risk of adverse drug reactions. For instance, older people have a decreased cardiac output both at rest and during exercise, weight loss, loss of elasticity of elastic vessels, a reduced number of functioning nephrons, poorer renal filtration capacity, decreased liver volume, a reduced number of functioning hepatocytes, decreased hepatic blood flow. These changes directly affect absorption, metabolism, distribution, and excretion of medicines, which in turn can affect their safety profiles. Consideration of age-related changes in the functions of body organs and systems, regular monitoring of the efficacy and safety of the prescribed medicine, changing the dosage regimen, and revision of the treatment sheet by healthcare professionals will help optimize pharmacotherapy and reduce the risk of adverse reactions and drug-induced diseases in older patients.

Experts of the Department for Evaluation of Medicinal Products’ Safety of the Scientific Centre for Expert Evaluation of Medicinal Products analysed administrative decisions of foreign regulatory authorities on the recall of medicines and/or the need to amend the prescribing information due to changes in their safety profile. The analysis helped to identify 11 administrative decisions that contain information on the following medicines registered in Russia: ranitidine, nizatidine, famotidine, pantoprazole, ondansetron, domperidone.

Purpose Preparation errors occur frequently during conventional preparation of parenteral medication in the clinical environment, causing patient harm and costs for the national health care system. The use of ready-to-administer prefilled sterilized syringes (PFSSs) produced by the hospital pharmacy can reduce preparation errors and the risk of bacteremia from contamination of the intravenous medication. The aim of this research is to compare the total costs of the conventional preparation method (CPM) with the PFSS method. Methods In this cost-minimization analysis, costs related to the preparation of the medication, bacteremia from contamination, adverse drug events as a result of preparation medication errors, and wastage of syringes were taken into account. Annual costs in a general Dutch hospital were consistently calculated. Three scenarios were analyzed: (1) all preparations as CPM (864,246 administrations per year), (2) all preparations as PFSSs, and (3) 50% as PFSSs and 50% as CPM. Deterministic and probabilistic sensitivity analyses were performed. Findings The first scenario found higher annual costs at €14.0 million (US$16.0 million) compared with the second scenario (€4.1 million, US$4.7 million). The most realistic situation (third scenario) found savings of €4.9 million (US$5.6 million) compared with the first scenario. Sensitivity analyses revealed that cost savings of PFSSs were strongly influenced by decreased risk of medication errors and contamination of intravenous medication. Extrapolating these results nationwide indicated potential savings of >€300 million (US$342 million) if only PFSSs were used. Implications The use of PFSSs prepared in the hospital pharmacy yielded cost savings compared with the CPM on the ward in the Dutch hospital.

While the presence of bovine spongiform encephalopathy (BSE) infectivity in the blood of clinically affected sheep has been proven by intraspecies blood-transfusion experiments, this question has remained open in the case of BSE-affected cattle. Although the absence of infectivity can be anticipated from the restriction of the agent to neuronal tissues in this species, evidence for this was still lacking. This particularly concerns the production and use of medicinal products and other applications containing bovine blood or preparations thereof. We therefore performed a blood-transfusion experiment from cattle in the clinical end stage of disease after experimental challenge with either classical (C-BSE) or atypical (H- and l-) BSE into calves at 4–6 months of age. The animals were kept in a free-ranging group for 10 years. Starting from 24 months post-transfusion, a thorough clinical examination was performed every 6 weeks in order to detect early symptoms of a BSE infection. Throughout the experiment, the clinical picture of all animals gave no indication of a BSE infection. Upon necropsy, the brainstem samples were analysed by BSE rapid test as well as by the highly sensitive Protein Misfolding Cyclic Amplification (PMCA), all with negative results. These results add resilient data to confirm the absence of BSE infectivity in the donor blood collected from C-, H- and l-BSE-affected cattle even in the final clinical phase of the disease. This finding has important implications for the risk assessment of bovine blood and blood products in the production of medicinal products and other preparations.

The problem of dosing drugs at an early age is conditioned by specific metabolism of medicinal products (MP) in the child's body. Currently, there are a few clinical trials on the study of physiological characteristics in different periods of childhood and systematised data. It is still relevant to understand the characteristic differences that affect the bioavailability, distribution and excretion of MP, especially in children over one month of life. The results of such studies are necessary in order to formulate the recommendations for use of MP in children taking into account their age and compensate for the lack of data from direct clinical trials in pediatrics. The possibility of using a dose calculation method regarding the fat content of the body in different periods of childhood and the chemical properties of the substance has been discussed.

The article reviews the literature on classical and atypical Reye’s syndrome, explores the circumstances that contribute to its occurrence, provides criteria for diagnosing with an illustration in the form of an authentic case of Reye-like disease in a child of 3 years old. Reye’s syndrome is a disease manifested by acute encephalopathy in combination with fatty degeneration of the internal organs, mainly the liver. This condition was first described in 1963 by an Australian pathologist who identified 21 cases of the disease in children with influenza A who were taking acetylsalicylic acid, 17 children died. In the future, the circle of infections that preceded the development of Reye’s syndrome-acute respiratory infections, chickenpox, entero- and rotavirus infections, in rare cases, hepatitis A and HIV, bacterial infections: mycoplasma, chlamydia, whooping cough, shigella, salmonella. Drugs that can cause the development of this syndrome: tetracycline, zidovudine, diclofenac sodium, mefenamic acid, paracetamol, amiodarone, warfarin, phenothiazine derivatives, histaminolytics (dimedrol), valproic acid. Along with drugs, insecticides, herbicides, hepatotoxic fungi can be used as triggers of the syndrome. There is an age dependence of the development of this syndrome. The pathogenesis of classic Reye’s syndrome is associated with generalized damage to the mitochondria primarily in the brain, as well as in the liver, kidneys, muscles, myocardium and pancreas, with the disturbance of oxidation of fatty acids in them and the formation of fat degeneration of varying degrees. In addition to the classic Reye’s syndrome, atypical Reye’s syndrome or Reye-like disease is isolated, occurs in children under 5 with congenital disturbance of oxidation of fatty acids. We observed in our clinic the case of Reye-like disease in a girl of three years with infection and taking antipyretics. In the discussion section, the features of the given case are noted, the question of the appropriateness (in view of the generality of the clinic and the mechanisms of development) of dividing the syndrome into classical and atypical is discussed. A new name for both conditions is proposed — Reye’s disease in honor of the discoverer, highlighting its two forms with an early and late onset. Given the morphological changes in this syndrome — steatosis of internal organs — authors seem to be appropriate measures aimed at treating secondary mitochondrial insufficiency and fatty dystrophy.

24–27 ноября 2020 г. в онлайн-формате состоялась научно-практическая конференция «Со­вре­менные подходы к экспертизе лекарственных средств» (РегЛек 2020).

A variety of medicinal products have been associated with rash and normally this information should be available in the Summary of Product Characteristics (SmPCs). Our study aimed to investigate the frequency of rash as an adverse drug reaction, based on the information provided by SmPCs of 1,048 single active substances (international non-proprietary names) authorized in the United Kingdom. Data on rash frequency was collected from each SmPC using automated searches based on selected keywords. Data analysis was carried out using R, v. 3.4. We found that over 90% of the medicines used orally or by injection may be associated with rash as an adverse event, the most common classes being protein kinase inhibitors, anticancer medicinal products, monoclonal antibodies, biologicals, antivirals and retinoids, with high variations in rash frequency for products within the same class, but also for products with the same active substance. Analysis of SmPCs revealed the need to increase homogeneity in reporting rash frequency, by using Council for International Organizations of Medical Sciences classification, and Medical Dictionary for Regulatory Activities coding in a more standardized manner, and also the need to include more safety endpoints in clinical trials and to use better the safety results for publication and updating the SmPCs.

The aim of the article is to present the legal conditions of one of the elements of the pharmacovigilance system (pharmacotherapy safety) – post-authorisation safety studies of medicinal products. The analysis embraced requirements and principles of conducting safety tests of medicinal products after the authorisation for admitting them to trading in the light of, in particular, the Pharmaceutical Law of 6 September 2001. Celem artykułu jest przedstawienie prawnych uwarunkowań jednego z elementów systemu pharmacovigilance (bezpieczeństwa farmakoterapii) – porejestracyjnych badań bezpieczeństwa produktów leczniczych. Analizie poddano wymogi oraz zasady prowadzenia badań bezpieczeństwa produktów leczniczych po wydaniu pozwolenia na dopuszczenie ich do obrotu w świetle obowiązujących przepisów prawnych, w szczególności ustawy z dnia 6 września 2001 r. Prawo farmaceutyczne.

Today, bronchial asthma is the most widespread childhood chronic respiratory disease in the world. To make managerial decisions in the health care system of Ukraine and to identify priority areas for the response to this disease, it is necessary to carry out a quantitative analysis of the appointment letters and the proportion of patients who received specific drugs for determining the main areas of therapy. Aim.Carrying out of frequency analysis of medical prescriptions at pharmacotherapy of bronchial asthma in children. Materials and methods.574 medical cards of an indoor patient with the main diagnosis of "Bronchial asthma", received at the Kyiv City Children's Clinical Hospital №2. A retrospective frequency analysis of the prescribing of drugs for archival data of appointment letters was conducted. Results.The conducted analysis of patients by age and sex allowed to establish the correspondence of the obtained results with the results of previous scientific studies on gender differences in the prevalence of bronchial asthma in children. In 45.3 % of the children, the length of stay was 2-10 days, and in 37.3 % – 11–20 days, indicating a sufficiently long period of inpatient treatment. According to the letters of appointment in the medical records of the inpatient patient, the physicians carried out 1983 appointments, of which 1867 were medicated (94.2 %), and 116 were non-medicated methods (5.8 %). The medical appointments of doctors included 1763 medicines. Of these, 94.4 % are medicines belonging to 11 groups according to ATC classification, 1.5 % – solutions for washing, irrigation, treatment, 0.3 % - dietary supplements, 0.1 % – homeopathic preparations, 3.7 % – other. The data that was obtained when calculating the intensity of the target varies in the range of 0.0006 to 0.07. The highest rates had only 2 drugs – Ventolin nebuli and Pulmicort, which were available in 22.3 % and 23.0 % of the patient's medical cards respectively, that is, every fifth patient. It was found that the ratio of drugs of domestic and foreign manufacture is 34.2 % (20 pharmaceutical companies) and 65.8 % (25 producing countries), respectively. Conclusions.The received data of the conducted analysis of prescriptions of medicinal products allow establishing a significant nomenclature of medical appointments for children with bronchial asthma. The promising direction for domestic pharmaceutical companies in the production of drugs for the treatment of the examined nosology was revealed. At the same time, the frequency analysis of the nomenclature of drugs can be used in the selection of drugs for reimbursement programs and medical insurance after further pharmacoeconomic studies.

Anna Staniszewska,1 Marta Dąbrowska-Bender,2 Dominik Olejniczak,2 Aneta Duda-Zalewska,2 Magdalena Bujalska-Zadrożny3 1Department of Experimental and Clinical Pharmacology, 2Department of Public Health, 3Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland Aim: The aim of the study was to assess patient knowledge on reporting of adverse drug reactions.Materials and methods: A prospective study was conducted among 200 patients. The study was based on an original survey composed of 15 single- and multiple-choice questions. The study involved individuals who have experienced adverse reactions as well as individuals who have never experienced any adverse reactions; people over the age of 18; literate; residing in Mazowieckie Voivodeship, who have not been diagnosed with any disease that could compromise their logical thinking skills.Results: The respondents who lived in the city had a greater knowledge compared to the respondents who lived in the countryside (Pearson’s χ2=47.70, P=0.0013). The respondents who lived in the city were also more statistically likely to provide a correct answer to the question about the type of adverse reactions to be reported (Pearson’s χ2=50.66, P=0.012). Statistically significant associations were found between the place of residence of the respondents and the correct answer to the question about the data that must be included in the report on adverse reactions (Pearson’s χ2=11.7, P

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient’s safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as “low-intervention clinical trial”. The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects’ safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Two simple, sensitive, selective, precise, and accurate methods for determination of trimethoprim in different sulfonamide formulations intended for use in human and veterinary medicine were optimized and validated. The methods are based on the trimethoprim reaction with bromcresol green (BCG) and 2,4-dinitro-1-fluorobenzene (DNFB). As extraction solvents we used 10 % N,N-dimethylacetamide in methanol and acetone for both methods, respectively. The colored products are quantified applying visible spectrophotometry at their corresponding absorption maxima. The methods were validated for linearity, sensitivity, accuracy, and precision. We tested the method applicability on four different medicinal products in tablet and powder forms containing sulfametrole and sulfamethoxazole in combination with trimethoprim. The results revealed that both methods are equally accurate with recoveries within the range 95-105 %. The obtained between-day precision for both methods, when applied on four different medicinal products, was within in the range 1.08-3.20 %. By applying the F-statistical test (P

The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO4. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide) was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100–800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.

Topic of the thesis: study of demand of herbal remedies to treat neural disorders The aim of the thesis: To conduct a study of demand of herbal remedies used to treat neural disorders. Objectives: To analize the range and variety of the herbal remedies used to treat nervous disorders in Lithuanian pharmacies. To elucidate factors which may have influence when choosing herbal remedies to treat nervous disorders. To reveal the main medical plants used to make remedies for manufacturing remedies for nervous disorders. To analise the opinion survey regarding herbal remedies used for treatment of nervous disorders. Methodology: The study was conducted using questionnaire starting March, 2015 until August, 2015. Descriptive and graphic methods were used to evaluate and analize results. Results: The survey revealed that 60 % of questioned women and 40 % of questioned men were affected by anxiety, stress or insomnia. 40 % of interviewees would choose herbal remedies as a suplement to chemical drugs. Conclusion: Conducted analysis of the range of the herbal remedies used to treat neural disorders which show that the most popular herbal remedies used to treat neural for nervous disorders are: Valerian tincture Valentis, oral solution 50 ml, Sedatif PC N40 tablets, Valeradix N60 tablets. The research showed that the majority of respondents were choosing herbal remedies to treat neural disorders mainly based on sales promotions. Respondents were using such remedies as an addition to the synthetic drugs and to lessen the side effects. Respondents scored these herbal remedies for nervous disorders as per advice of the doctor or pharmacist. Hop, St. John‘s Wort, Lavender, Melissa, Marjoram, Oregano, Maypop, Chamomile, Valerian, Leonurus are the most popular plants used to prepare herbal remedies to treat neural disorders. This research shows how relevant this problem is among different age groups in our society. More than the half of female respondens and a quarter of males respondents were experiencing anxiety, stress, tension, insomnia. Only a small share of the respondents were not complaining about any neural disorder.