This article is a continuation of the publication «Standard form of a Periodic safety update report» in the previous issue of the journal. This article recommendations for the preparation of Periodic safety update report (PSUR) to ensure the development of this report document license holders of certificates of registration of drugs for subsequent submission to the section «Periodic report» Federal Database «Automated system of Pharmacovigilance» and subsequent evaluation of the Roszdravnadzor the information of scientific and clinical nature are presented. This practical advices with step by step recommendations for medical authors are presented.

The article is devoted to the problems of safety of non-steroidal anti-inflammatory drugs. The analysis of 3,963 spontaneous reports to the Russian database for the period from December 7, 2008 to August 31, 2017, with the aim of identifying information on adverse reactions that have occurred during the application of NSAIDs is presented. Most often unwanted reactions were registered for preparations of acetylsalicylic acid, diclofenac, ibuprofen, ketorolac. A total of 6,257 adverse reactions were recorded. The greatest specific weight among all cases of undesirable reactions were disorders of the immune system, skin, subcutaneous tissues and gastrointestinal tract. The lack of therapeutic effectiveness of drugs was recorded in 280 cases. Most often, such ADR on NSAIDs were angioedema, urticaria, erosive gastritis, skin rash, increased blood pressure. In case of using of the over-the-counter drugs and self-medication it is necessary to work with the population to form a responsible attitude to the use of medicines, warn of possible complications of self-medication and conditions requiring compulsory medical attention.

Varenicline is a partial agonist of nicotinic acetylcholine receptors for the therapy of nicotine addiction. The efficacy and safety of the use of varenicline in the treatment of nicotine dependence have been demonstrated in clinical trial EAGLES. These studies describe adverse reactions such us mental disorders: depression, suicidal thoughts, suicidal behavior. However, data on the increase in the incidence of these adverse reactions during longer treatment with varenicline was not obtained. In 2016, the FDA has been presented with information about the risk of development the following serious neuropsychiatric adverse reactions on the using of varenicline: depression, manic syndrome, psychosis, hallucinations, delusions, homicidal ideation, aggression, agitation, anxiety, panic, suicidal ideation, attempt of suicide. These adverse reactions were observed in patients with and without psychiatric disorders.

Generic drug of fingolimode (Nesklair, Russia) receives marketing authorisation in 2014. In 2016, was initiated the Post-authorisation safety study (PASS) to evaluate the safety of Neskler in patients with remitting multiple sclerosis (MS) vs. original drug and in the primary assignment. This PASS was conducted at 8 clinical centres in 7 regions of Russia — Moscow, Moscow region, St. Petersburg, Rostov-on-Don, Ufa, Chelyabinsk, Kurgan. The results of therapy of MS in 94 patients of both sexes, aged 35 ± 8.9 years, who have got fingolimode for 12 months are presented. The average duration of disease at inclusion in the study was 8.6 ± 4.9 years. 74,47 per cent (1 group) received this therapy with the original drug, 25.53 per cent of patients (group 2) have not received previous fingolimode. The results of the program indicate a good safety profile, comparable with previously published data on the use of the original drug.

One of the key enzymes involved in the first phase of biotransformation of drugs is cytochrome P450 (CYP450), represented predominantly in the liver. Vincristine is metabolized mainly by CYP3A5 (75 %) and to a lesser extent CYP3A4 (whose level is lower in children). Low expression (CYP3A5*3 genotype) or even absence of CYP3A5 (in 80 % of Caucasians) and an age-related decrease in CYP3A4 activity leads to a five-fold decrease in vincristine clearance, its cumulation and development of an undesirable side reaction (CPD) — most often peripheral neuropathy, but its characteristic feature is the reduction of achilles reflexes and distal paresis after 2–3 injections. The article presents a case of a rare side effect of vincristine — damage to the nervous apparatus of the intestine with the development of dynamic obstruction. The complication of vincristine therapy is explained by the ethno-dependent decrease / absence of cytochrome P450 3A5, which metabolizes vincristine, which leads to cumulation of the drug.