Herbal medicines make up a large part of all medicinal products in the Russian market. Complex combinations of biologically active substances that are used as components in herbal medicines not only determine their therapeutic efficacy, but can also cause adverse reactions. The aim of this review was to analyse data on adverse effects of herbal medicines, and reasons and mechanisms behind their development. Special attention should be given to hepatotoxic and nephrotoxic effects of biologically active substances that are used as components in herbal medicines, because liver and kidney failure may lead to life-threatening conditions. The paper addresses hepatic adverse effects, including sinusoidal obstruction syndrome, caused by toxic biologically active substances of the pyrrolizidine alkaloids group. The paper summarises data on herbal medicines and toxic biologically active substances causing acute kidney injury and chronic kidney disease. It analyses potential clinically significant interactions that may occur during co-use of herbal and other types of medicines due to their pharmacokinetic and pharmacodynamic interactions. Further research involving collection, systematisation, and analysis of adverse effects of herbal medicines used alone or in combination with other medicinal products is needed to improve the safety of pharmacotherapy.

Atrial fibrillation is a serious adverse reaction associated with the use of anticancer drugs. The aim of the study was to analyse scientific literature on the prevalence, pathophysiological mechanisms, and risk factors of anticancer drug-induced atrial fibrillation, ways of its prevention and treatment. The results of the study showed that the incidence of drug-induced atrial fibrillation varies depending on a specific anticancer drug and ranges from 1 to 86%. It is associated with the use of herbal anticancer agents, alkylating agents, protein kinase inhibitors, monoclonal antibodies, immunosuppressants, antitumor antibiotics, antimetabolites, hormonal anticancer agents, hormone antagonists, etc. Most often, atrial fibrillation develops following the use of such drugs as gemcitabine (in combination with vinorelbine), cisplatin, melphalan, ibrutinib, cetuximab, trastuzumab, alemtuzumab, and doxorubicin. It was demonstrated that the pathophysiological mechanisms underlying the development of atrial fibrillation induced by anticancer drugs include electrophysiological abnormalities, myocardial injury, inflammation, immune response, apoptosis, and oxidative stress. Risk factors for the development of anticancer drug-induced atrial fibrillation are not clearly defined yet and continue to be the subject of research. Prevention of drug-induced atrial fibrillation in cancer patients requires a multidisciplinary approach involving participation of an oncohematologist and a cardiologist. The doctors in charge should also be vigilant regarding potential development of this adverse reaction.

The Russian Federation and the member states of the Eurasian Economic Union (EAEU) are working on the creation of a common pharmaceutical market. EAEU marketing authorisation may be granted to those pharmaceutical companies whose activities comply with the Good Pharmacovigilance Practice (GVP). The aim of the study was to analyse pharmacovigilance system documents submitted as part of registration dossiers of medicines and to identify problems that may arise during preparation of the pharmacovigilance system master file (PSMF). The authors analysed the PSMF, which makes part of the registration dossier, for compliance with the EAEU GVP requirements for submission, content, and completeness of all sections of the document. They identified the most common types of errors in PSMF preparation and analysed conditions when a PSMF is required or, alternatively, when a brief summary of the pharmacovigilance system of the marketing authorisation holder will suffice. The paper summarises specific aspects of incorporating pharmacovigilance system documents in regulatory submissions, as well as aspects of presenting pharmacovigilance system data when bringing the registration dossier in line with the EAEU requirements. This information may be useful for marketing authorisation holders who are the main stakeholders in the medicine authorisation process and who are directly involved in the pharmacovigilance system management during the authorisation and post-authorisation stages of the drug life-cycle.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used worldwide as pain relievers, antipyretics, and anti-inflammatory drugs. Failure to comply with the instructions for medical use of this group of drugs increases the risk of serious adverse reactions on the part of different organs and systems. From 5 to 18% of patients taking NSAIDs develop adverse reactions associated with impaired renal function. Organic anion transporter (OAT) proteins, which mediate the drug excretion with urine, have an important role to play in the NSAIDs adverse effect on kidneys. The aim of the study was to analyse and systematize scientific literature on the role of OATs in nephrotoxicity development in the context of NSAIDs use. It was revealed that adverse kidney reactions associated with NSAIDs are determined by several mechanisms, including inhibition of prostaglandin synthesis due to cyclooxeganse-1 and/or cyclooxeganse-2 blockade, and direct toxic effect on renal tubule epithelium followed by tubular necrosis due to NSAIDs interaction with OATs. Moreover, by suppressing OAT1 and OAT3, NSAIDs can not only enhance, but also reduce nephrotoxic effects of other medicines (when used together) and endogenous/exogenous toxins. Considering that NSAIDs are widely used in the treatment of various diseases (including in elderly patients and patients with concomitant renal diseases), it is still relevant to study mechanisms of adverse kidney reactions associated with drug transporters.

Doctors of various medical specialties often encounter adverse drug reactions in their clinical practice. Methotrexate (MTX) can cause adverse reactions in the oral cavity, primarily erosions and ulcerations. The aim of the study was to analyse scientific literature on the prevalence, pathophysiological mechanisms, risk factors for oral lesions associated with low doses of MTX, their prevention and treatment. It was demonstrated that the most frequent oral adverse reactions associated with low doses of MTX are hard-to-heal painful necrotic and often irregularly shaped lesions of the oral mucosa (including aphthae and ulcers). The spectrum of histopathological changes ranges from nonspecific ulcerations to lichenoid reactions. Treatment of oral lesions induced by low doses of MTX consists in drug withdrawal or dose tapering. Folic acid and local symptomatic therapy can also be used, if necessary. Practitioners should be aware of the potential development of MTX-induced oral lesions, and specific aspects of the drug pharmacokinetics and pharmacodynamics in order to be able to ensure timely detection of adverse reactions and their effective treatment.

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 limiting the use of some medicinal products and/or the need to introduce changes in patient information leaflets due to changes in the medicines’ safety profiles. The analysis helped to identify 16 administrative decisions that contain information on the following medicines registered in Russia: duloxetine, sertraline, paroxetine, сitalopram, desvenlafaxine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, venlafaxine, vortioxetine, mirtazapine, risperidone, clozapine, aripiprazole, quetiapine, olanzapine, lacosamide, gabapentin, pregabalin.