Drug-induced neutropenia and agranulocytosis are serious and potentially life-threatening complications of pharmacotherapy. The aim of the review was to systematise and analyse scientific literature on the prevalence, risk factors, pathogenesis, clinical picture, methods of prevention and treatment of drug-induced neutropenia and agranulocytosis, and medicinal products that most often lead to their development. The analysis revealed that one of the major reasons of drug-induced neutropenia and agranulocytosis is the use of cytotoxic drugs (alkylating agents, antimetabolites, taxanes), non-steroidal anti-inflammatory drugs, antibiotics, antiplatelet, antithyroid, antirheumatic, antiarrhythmic, and antipsychotic drugs. The incidence of drug-induced neutropenia and agranulocytosis is generally low—from 3 to 16 cases per 1 million patients annually. The main risk factors for the development of these conditions include old age, female sex, history of chemotherapy or radiation therapy, malnutrition, and comorbidities. The symptoms in patients with neutropenia and agranulocytosis regardless of etiology can include fever, chills, apathy, myalgia, weakness, pharyngitis, gingivitis, sinusitis, stomatitis, bronchitis, and sepsis. There are no practical methods for early diagnosis or prevention of drug-induced neutropenia and agranulocytosis. Successful management of these conditions relies on timely identification and immediate withdrawal of the potential causative drug. Prevention of chemotherapy-associated neutropenia may consist in reducing the dose of the chemotherapeutic agent. Practicing physicians should be aware of the risk of drug-induced neutropenia and agranulocytosis. It is important to raise awareness among healthcare professionals of the methods of diagnosis and prevention of these conditions, as well as specific aspects of managing patients with these conditions.

About 14‒23% of all clinically used drugs have nephrotoxic potential and are a frequent cause of acute and chronic kidney problems. Acute kidney injury (AKI) is associated with a high risk of repeat hospitalisation, complications, and mortality in adults and children. The aim of the study was to provide an overview of the current approaches to the assessment of drug induced nephrotoxicity. The paper summarises pathogenetic mechanisms of drug induced kidney injury as well as molecular mechanisms at the drug transporters level. It analyses risk factors for drug induced kidney injury—age, sex, ethnicity, comorbidities (chronic kidney disease, diabetes, cardiovascular disease, immune disorders, sepsis, etc.), drug dosage and duration of therapy, pharmacokinetics of drugs, combinations of potentially nephrotoxic drugs, genetic determinants of drug metabolism and transport, etc. It was demonstrated that the traditional nephrotoxicity markers—serum creatinine and urine output—have low sensitivity as indicators of early renal damage. Therefore, new kidney biomarkers are being sought for in order to be used in AKI diagnosis and monitoring in patients with different comorbidities. Some of these biomarkers are already used in drug development, preclinical and clinical trials for assessment and prediction of drug safety. The analysis showed that none of these new kidney biomarkers could be used as an all-purpose tool in routine clinical practice. The development of new AKI biomarkers is a long-range objective and is the path toward early diagnosis and successful treatment of drug-induced nephrotoxicity.

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.

Cervical cancer caused by human papillomavirus (HPV) types 16 and 18 is one of the most common cancer types in women. Other high-risk HPV types may cause vaginal cancer, vulval cancer, penile cancer, anal cancer, head and neck cancer. Low-risk HPV types, such as 6 and 11, can cause anogenital warts and recurrent respiratory papillomatosis. These diseases may be prevented by vaccinating women and men before contracting the virus. The aim of the study was to summarise current data on using vaccines for the prevention of HPV-associated diseases. Currently, there are three HPV vaccines available on the market: Cervarix^®, Gardasil^®, and Gardasil^®9. Extensive clinical and post-licensing studies show that these vaccines are safe and highly effective (up to 100 %) in preventing vaginal, vulval, and cervical intraepithelial neoplasias when administered to patients who were not previously infected with these HPV types. However, there are a number of unresolved issues that encourage further clinical research to find a universal vaccine. First of all, the effectiveness of these vaccines is limited to the HPV types covered by a particular vaccine. It was only in 2011 that the question was raised about the need to vaccinate males. Also, the recommendations on the frequency of vaccination are periodically revised in line with new immunogenicity study results. Reducing the frequency of immunisation is particularly relevant for developing countries with limited financial resources and a high incidence of cervical cancer. Thus, global vaccination programmes, including those with optimal availability and immunisation frequency for developing countries, higher vaccination coverage in terms of age and sex, and expansion of cancer screening programmes are necessary to eliminate HPV worldwide.

Summary. Safety pharmacology studies of paediatric medicines are an important stage in the life cycle of drugs.

The purpose of the study was to analyse and compare the safety pharmacology profiles of the recommended paediatric dosage regimens of a fixed ibuprofen (IBU)/paracetamol (PAR) combination and of IBU and PAR monopreparations following repeated oral administration of these products to juvenile rats.

Material and methods: safety pharmacology was assessed in both male and female outbred juvenile rats. Two dose levels were used in the study—the highest treatment dose (HTD) equivalent for juvenile rats, and the three-times-equivalent therapeutic dose (3 HTD). The animals were given the fixed IBU/PAR combination in the form of suspension from dispersible tablets (100 mg IBU + 120 mg PAR), IBU in the form of oral suspension (100 mg/5 mL), and PAR in the form of oral suspension (120 mg/5 mL). Statistical processing was performed using Statistica 10.0 software.

Results: unlike monopreparations, the fixed IBU/PAR combination did not have clinically significant hepatotoxic or nephrotoxic effects when administered to juvenile rats. Administration of IBU alone resulted in an increase in blood urea nitrogen concentration in female rats (HTD) and male rats (3 HTD), and a small amount of leucocytes in the urine of female rats. Administration of PAR resulted in an increase in the amount of red blood cells in the urine of male rats. Administration of the monopreparations at the HTD dose led to a decrease in the locomotor activity of the animals. No significant effect on the cardiovascular or respiratory systems was observed for any of the products.

Conclusions: the safety pharmacology profile of the fixed IBU/PAR combination after repeated oral administration to juvenile rats did not differ much from those of IBU and PAR used alone, and in some cases was even better.

An important part of treating patients infected with SARS-CoV-2 is to ensure effective pathogenetic and symptomatic therapy before life-threatening complications, such as pneumonia, acute respiratory distress syndrome, or sepsis begin to develop. Current COVID-19 treatment protocols often use remdesivir and tocilizumab, though safety data on these drugs are insufficient. Therefore, experts of the Centre for Evaluation of Medicinal Products’ Safety of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation studied adverse reactions to remdesivir and tocilizumab, which are registered in the VigiBase (as of August 27, 2020), the global database of individual case safety reports.