The widespread use of statins in clinical practice necessitates a systematic approach to the risk and safety assessment. The aim of the study was to analyze information about adverse reactions to statins and their specific causes in patients with hypercholesterolemia accompanied by diabetes and hypothyroidism. The paper compares statin products (simvastatin, atorvastatin, pravastatin, rosuvastatin, and fluvastatin) in terms of the frequency of the most significant adverse reactions—statin-induced myopathy, liver damage, secondary hyperglycemia. It dis­cusses specific causes of adverse reactions to statins in patients with hypothyroidism and dia­betes. It was demonstrated that the use of statins in patients with compensated hypothyroid­ism, who have CC and TC allelic variants of the SLCO1B1*5 gene (c.521T>C), is associated with a higher risk of developing statin-induced myopathies. The adjustment of statin doses, especially in patients with hypothyroidism and diabetes, should be made based on the results of pharmaco­genetic testing for SLCO1B1*5 (c.521T>C) allelic variants. The results of dynamic clinical and laboratory control of the hepatic transaminase level, as well as the levels of glucose, glycated hemoglobin, and thyroid-stimulating hormone should be the key factors to be taken into account when adjusting treatment plans in this group of patients. The paper analyses polymorphisms of genes which are associated with resistance to statin therapy in patients with diabetes. Thus, the use of statins for primary prevention and treatment of cardiovascular diseases in patients with hypercholesterolemia accompanied by diabetes and/or hypothyroidism, requires a comprehen­sive assessment of the risk/benefit ratio.

EEosinophilia can be caused by various reasons, including taking certain medications, in which case it is called drug-induced. The relevance of drug-induced eosinophilia issue is due to the serious consequences associated with this condition, in particular eosinophilia-myalgia, DRESS-syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), heart damage and multisystem manifestations which can be fatal. Objective of this review is data analysis and systematization on the prevalence and risk factors for the drug-induced eosinophilia development, as well as a synthesis of existing methods for the prevention and treatment of this condition. Most often, drug-induced eosinophilia develops while taking certain antibiotics, sulfonamides, anti-malarial, anti-leprosy, anticonvulsant, non-steroidal anti-inflammatory drugs. The prevalence of drug-induced eosinophilia varies with the use of different drugs. This pathological condition occurs with the same frequency in both men and women of any age. Risk factors include the presence of several clonal hematological pathologies, non-hematological disorders (allergic and atopic diseases), infections (especially parasitic), tumors, as well as concomitant use of ≥2 of the above-mentioned drugs. The main way to prevent drug-induced eosinophilia is to refuse to use and/or replace the drug with another drug that does not have this side effect, provided the patient has clinical symptoms associated with eosinophilia. A symptomatic eosinophilia does not require the discontinuation of ongoing drug therapy. The presence of clinical symptoms associated with eosinophilia dictates the need for discontinuation of the drug, but if this is not possible, the treatment is continued with careful monitoring of the clinical picture and hematological parameters. 

For the treatment of dementia and Alzheimer’s disease, acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or the non-competitive inhibitor of N-methyl-D-aspartate receptors (NMDA receptors) memantine are currently used. The administration of these drugs can help temporarily improve or stabilize memory impairments and other cognitive functions, regress behavioral disorders, reduce the patient’s dependence on others, but at the same time can lead to the development of adverse drug reactions. The aim of this study was to analyze the information on the safety of acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the non-competitive inhibitor of NMDA receptors used to treat dementia. It was shown that stimulation of cholinergic receptors can lead to adverse drug reactions as contraction and narrowing of the pupil (miosis), an increase in lens curvature, accommodation spasm (visual impairment and an increased risk of falls), a decrease in heart rate (bradycardia) and inhibition of conduction of impulses through the conducting system heart, increased tone of the bronchi, gastrointestinal tract, gall and bladder, decreased tone of the sphincters of the digestive tract and bladder, increased secretion of exocrine and glands of the stomach, agitation, confusion. Blockade of NMDA receptors due to impairment of glutamate metabolism in the central nervous system may be the cause of neurotoxicity of NMDA receptor antagonists, and also causes dizziness, feeling of tiredness, hallucinations, drowsiness, and confusion. In case of development of adverse reactions, if possible, it is necessary to stop using the drug or reduce its dose, in case of an overdose or other need, prescribe symptomatic therapy. Information on the safety of cholinesterase inhibitors and NMDA receptor antagonists presented in the article is of practical importance for healthcare professionals, as it allows them to assess the possible risks associated with the use of drugs of these groups more accurately. In addition, the information can be used to optimize and individualize the pharmacotherapy regimens for patients with dementia, including the development of domestic protocols for the deprescribing of drugs (evidence-based practice of withdrawal, replacement or gradual dose reduction) in the elderly. 

Regulatory approaches to assessing the safety of homeopathic medicines in the Russian Federation and abroad are formed in accordance with regulatory acts, national and international rules and guidelines. Scientific literature is particularly important for justification of safety of homeopathic medicines. The purpose of this study was to determine the requirements and procedure for presenting justification of homeopathic medicines safety in the registration dossier in accordance with the documents of the Eurasian Economic Union and the European Union. According to the current Russian and foreign regulatory approaches the safety may be justified by scientific literature data on homeopathic use and by substantiation of the dosage in the case of medicines that have long experience of safe use and those that are authorized under a simplified procedure based on a dossier with a product instruction that does not establish indications for use. In both cases, there is no need to provide the results of preclinical or clinical studies of the drug. This approach reflects specific features of homeopathic medicines. An objective criterion of the safety of homeopathic medicines is the assessment of the dosage of active substances, taking into account the «first safe dilution» of homeopathic substances. A formal safety justification using registration data for similar drugs or additional information on the use of these pharmaceutical substances in homeopathy is also possible, but may be insufficient. The completeness and proper documentation of bibliographic data are the main criteria for an appropriate rationale for the safety of homeopathic products. 

A recent increase in the number of safety signals of varying quality being submitted to the national and industry databases calls for the development of formalized search and analysis algorithms. The aim of the study was to develop an approach to identification and evaluation of safety signals in the database of an expert institution containing notifications of serious adverse events (SAE) that occurred during clinical trials. A specific feature of this approach is that it can be used in limited databases which, unlike international databases containing millions of reports (VigiBase, EudraVigilance), preclude the use of statistical methods for measurement of disproportionality. The proposed approach consists in evaluation of several criteria: two discriminatory ones (the geographic location of the clinical trial site and the type of report — whether it belongs to clinical trial documents other than the CIOMS form), and four expert criteria (whether a serious adverse event is a serious adverse reaction, whether the serious adverse reaction is predictable or not, the degree of reliability of the cause-effect relationship, and the benefit-risk ratio). The application of this approach resulted in the development of the «Signals» module of the expert institution’s SAE database. The «Signals» module is designed to calculate the rating of safety signals which can be used for conclusive identification and management of safety signals, and provides basis for scientifically well-grounded expert decisions on the need for administrative action on the clinical trial or its further monitoring. The developed approach can be used in the industry, national, and international pre- and postauthorization pharmacovigilance databases.

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 profile, conducted by experts of the Scientific Centre for Expert Evaluation of Medicinal Products revealed 23 administrative decisions. These decisions contained information on the following medicines registered in Russia: аmitriptyline, duloxetine, quetiapine, lamotrigine, topiramate, phenytoin, articaine, epinephrine, bupivacaine, oxybutynin, dexlansoprazole, pantoprazole, esomeprazole, famotidine, ketoconazole, minocycline, quinolone and fluoroquinolone (cinoxacin, ciprofloxacin, flumequine, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin, pipemidic acid, prulifloxacin and rufloxacin), antiretrovirals (abacavir, abacavir, dolutegravir, lamivudine, zidovudine, atazanavir, cobicistat, emtricitabine, tenofovir, darunavir, didanosine, rilpivirine, efavirenz, enfuvirtide, etravirine, fosamprenavir, indinavir, lopinavir, ritonavir, maraviroc, raltegravir, rilpivirine, nevirapine, saquinavir, tipranavir), direct-acting antiviral drugs (daclatasvir, dasabuvir, elbasvir, grazoprevir, glecaprevir, pibrentasvir, sofosbuvir, ombitasvir, ritonavir).