The review article presents a summary of adverse drug reactions (ADR)  in children, information about which was received in 1968–2018 in the International database VigiBase (Uppsala monitoring center, UMC).  Of the  18.4 million Individual Safety Case Reports (ICSR)  received over  50 years by VigiBase, 1.47 million ICSR contain information on the  safety of pharmacotherapy in patients under the  age of 18,  including: 34 510  reports contain information on ADR  in children under the  age  of 27 days, 415  678  — in children aged  28 days  to 23 months, 613 676 — aged 2 to 11 years and 405 202 ICSR — in patients aged 12 to 17 years inclusive. During 2018  141 655 ICSR ADR of children in VigiBase was received. The most common reason for submitting reports on adverse effects in children was vaccines, antibiotics, non-steroidal antiinflammatory drugs, analgesics-antipyretics, anti-acne and valproic acid. The most common side effects of drugs in children were the following ADR: hyperthermia, rash, vomiting, nausea, urticaria, diarrhea, itching, headache, erythema at injection site, convulsion. Separate data on 6 age groups about 10 most frequent ADR in children and  about 10 medicines which ICSR most often arrived in VigiBase for 50 years and for 2018  are given.

New oral  anticoagulants are  effective for  the  prevention of thromboembolic complications in patients with atrial fibrillation, or after orthopedic surgery. The use  of these drugs may be associated with the  risk of bleeding from the  gastrointestinal tract — a dangerous complication, which can potentially lead  to death. The aim of this research was systematization and analysis of information on the interactions of new oral anticoagulants with other drugs and food products, and  the  identification of potentially dangerous combinations that increase the  risk of gastrointestinal bleeding. To assess the  risk of a heavy bleeding in patients with atrial fibrillation taking oral  anticoagulants to  prevent thromboembolic complications, HAS-BLED scale  is used. In some  cases  activated partial thromboplastin time, ecarin clotting time, anti-FXa, etc. can  be used  to assess the  effectiveness of the  oral  anticoagulants. Potential combinations that increase the  risk of  bleeding include the  simultaneous administration of  new  oral  anticoagulants with antiplatelet agents, anticoagulants, including vitamin K antagonists, unfractionated heparin, low molecular weight heparins, nonsteroidal anti-inflammatory drugs, antidepressants along with other drugs and foods (curcumin, grapefruit juice, peppermint, eucalyptus, etc.). The administration of proton pump inhibitors, as well  as the  elimination of potentially dangerous combinations of drugs and  food with new oral  anticoagulants, can help  prevent gastrointestinal bleeding.

Due  to repeated reports of adverse effects with the  use  of fluoroquinolone antibiotics,  these drugs become  over  and  over  again the  object of the  close  attention of pharmacovigilance  specialists and  health care  specialists. The aim: to study the  frequency and  the  nature of adverse reactions associated with the  use  of ciprofloxacin, based  on the  analysis of the  spontaneous reports received by  the  Russian pharmacovigilance service. Materials and  Methods: A retrospective analysis of the  spontaneous reports of ciprofloxacin was conducted on the  data-base «Pharmacovigilance» of the  automated information system of Roszdravnadzor from 2008 to 2018. Results: 3403  adverse reactions that occurred in 2083  patients using ciprofloxacin were recorded. The  most frequently developed reactions were  from skin and  subcutaneous tissues (37.3 %), general disorders and  disorders at the  injection site (21.1 %), gastrointestinal tract reactions (14.9 %). More than a one third of the  reports contained information about serious adverse reactions. Unexpected reactions were identified as not  recorded in the  instructions for the medical use of ciprofloxacin: bradycardia, atrial arrhythmia, cyanosis, increased blood pressure. Conclusions: fluoroquinolone antibiotics with proven efficacy and years of experience in clinical use, continue to be drugs whose  safety requires constant monitoring. The  results of the  study confirmed the  possibility of detecting a wide  range of the  adverse reactions using the  method of spontaneous reports. Regulatory authorities of the  Russian Federation should recommend to registration certificate holders to include the  information of adverse reactions of ciprofloxacin that were registered in the  post-marketing period in the  instructions for medical use.

Multiple sclerosis is  one  of  the  most common neurological diseases of  working age population. The last 20 years widely use drugs that change the  course of multiple sclerosis. The article is devoted to the  problems of the  safety of treatment of multiple sclerosis with interferon beta  drugs. The aim of the study was to analyze the  adverse drug reactions (ADRs)  of interferon beta  medicines and  the  assessment of the  possibility of identify signals on rare adverse drug reactions based  on spontaneous reporting data. A retrospective analysis of reports of ADRs that occur after the  use of interferon beta-1a, interferon beta-1b was performed. The results confirm the known risks of developing ADRs of this group of drugs: general disorders and administration site conditions, nervous system disorders, musculoskeletal and  connective tissue disorders and psychiatric disorders. Under-reporting of ADR  was  identified, high level  reporting rate from manufacturers was  detected. A significant number of received spontaneous reports contained information about serious ADRs  (52.9 % — for  interferon beta-1a; 29.4 % — for  interferon beta-1b). All ADRs corresponded to those specified in the  instructions for  medical use of drugs. The results of the  study confirmed the  possibility of identifying signals associated with the  occurrence of very common, common, and uncommon ADRs, such  as thrombocytopenia.

Presently, an active search for  modern drugs for  the  treatment of multiple sclerosis is ongoing. Since  the  treatment with original drugs is expensive, therefore, the  development of local biosimilars is underway, which at a lower  cost should be effective and safe  as original ones. The aim of the study  is to compare the  safety of foreign preparations of interferon beta-1b (Betaferon and  Ekstavia) with Russian biosimilars (Ronbetal®, Infibeta®) in the  treatment of multiple sclerosis to ensure the  possibility of import substitution. In the  present study the  safety of domestic interferon beta-1b biosimilars in the  treatment of multiple sclerosis was studied using a meta-analysis method. There were 3 studies included in the meta-analysis. A total of 778 people participated in the  study. The average age of the  subjects was 35.92 ± 9.57 years. The main inclusion criteria were a reliable diagnosis of remittent or secondary progressive multiple sclerosis with exacerbations, an  EDSS score  less  than 5.5. The  subjects were  divided into 2 groups: the first group received therapy with the  Russian biosimilars of interferon beta-1b (Ronbetal®, Infibeta®), the  second — the  foreign ones (Betaferon, Extavia) in therapeutic doses. The duration of therapy was at least 6 weeks. Results. A meta-analysis of three studies showed the  following data: the difference in the frequency of local complications such as hyperemia in patients who received Russian and  foreign interferon beta-1b analogues statistically insignificant, the  relative risk is 1.243 (p > 0.05). No statistically significant differences in the frequency of influenza-like syndrome were  also  detected: the  relative risk is 1.459 (p > 0.05). Conclusion. This  study has increased the power of the evidence base in the application of Russian biosimilars. The conducted meta-analysis showed the absence of a statistically significant difference in the incidence of such side effects as the  injection site hyperemia and the  influenza-like syndrome in domestic biosimilars of interferon beta-1b compared with foreign ones.

Analysis of  recommendations of  foreign regulatory authorities on  the  restriction of  circulation 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 25 administrative decisions of foreign regulatory authorities. These  decisions contained information on the  following medicines registered in Russia: apixaban, granulocyte-macrophage colony  stimulating factor, hydroxyethyl starch, dabigatran, eltrombopag, epoetin alfa, atypical antipsychotic drugs, benzocaine, varenicline, carbamazepine, lamotrigine, suvorexant, topiramate, aztreonam, azithromycin, isoniazid, caspofungin, miconazole, meropenem, atazanavir, dolutegravir, lamivudine, efavirenz.