A. E. Krasheninnikov General Director of ANO “National Scientific Center for Pharmacovigilance”, Moscow, anatoly.krasheninnikov@drugsafety.ru

A. V. Matveev, Associate Professor of the Department of Internal Medicine No. 1 with the course of clinical pharmacology of the Medical Academy S. I. Georgievsky Federal State Autonomous Educational Institution of Higher Education “Crimean Federal University. V. I. Vernadsky”, Simferopol, Executive Director of ANO “National Scientific Center for Pharmacovigilance”, Moscow, avmcsmu@gmail.com

E. A. Egorova Assistant of the Department of Internal Medicine No. 1 with the course of clinical pharmacology of the Medical Academy. Assistant of the Department of Internal Medicine No. 1 with the course of clinical pharmacology of the Medical Academy. S. I. Georgievsky Federal State Autonomous Educational Institution of Higher Education “Crimean Federal University. V. I. Vernadsky”, Simferopol, elena212007@rambler.ru

Currently, nuclear medicine technologies related to the use of radioactive sources for diagnostic and therapeutic purposes are widely introduced into the practice of doctors. Of particular importance is the use in clinical practice of means for determining the state of various organs and systems of the body, such as radiopharmaceuticals (RP). Radiopharmaceuticals are medicines that contain one or more radionuclides (radioactive isotopes) in a ready-to-use form. The history of the use of radioactive isotopes in scientific research began in 1913 by D. Hevesy. In 1927, H. L. Blumgart and S. Weiss were the first to use the radioactive isotope radon for diagnostic purposes to determine blood flow velocity.

The widespread use in medicine of drugs containing radionuclides began in the 1940s. To date, about 200 types of radiopharmaceuticals of various prices are represented on the world pharmaceutical market, the consumption of which is growing by 10–15% annually. The market leaders are the countries of the Asia-Pacific region, Europe and North America, including the USA. A study of the dynamics of consumption of this group of drugs in the United States alone showed that by 2020 the volume of the radiopharmaceutical market is projected to amount to $20 billion, which will be 20 times higher than in 2001. In the Russian Federation, there is a trend similar to other countries to increase the cost , volumes of production and use of radiopharmaceuticals. According to the State Register of Medicines of the Russian Federation, 22 radiopharmaceuticals for scintigraphy and single-photon emission computed tomography (SPECT), 20 radio kits for immune analysis and 6 radiopharmaceuticals based on 4 ultrashort-lived radionuclides for positron emission tomography have been registered. A study by authorized persons for pharmacovigilance of the use of radiopharmaceuticals in clinical practice showed that about 95% of drugs in this group are used for diagnostic purposes, and 5% for radionuclide therapy.

The diagnostics of diseases with the help of radiopharmaceuticals is based on the principle of indication, which makes it possible to monitor the distribution of the radionuclide included in its composition in the body by external registration of radiation with further study of biological and physiological processes. Radiopharmaceuticals can selectively accumulate in the intravascular, extracellular and other spaces of the body, which makes it possible to detect structural and functional changes in organs and tissues at the earliest stages of development. The basis of radionuclide therapy is the formation of absorbed doses of ionizing radiation in pathological foci, which leads to damage to vital components of tumor cells and destruction of damaged tissue. This finds its application in the treatment of tumor diseases of the musculoskeletal system, the thyroid gland, in the formation of bone metastases of tumors of various localizations.

The RFP circulation is carried out in accordance with the requirements established by the legislation in the field of ensuring the radiation safety of the population. Radiopharmaceuticals can be supplied to health care facilities in the form of ready-to-use forms or in the form of kits for preparation in medical institutions to reduce cost. In the latter case, radiopharmaceuticals are prepared in the laboratory from a set of reagents and a radioactive label immediately before use. Order No. 211n dated April 27, 2015 “On approval of the procedure for the manufacture of radiopharmaceutical drugs directly in medical organizations” regulates the need for the manufacture of radiopharmaceuticals in medical organizations in controlled areas that meet the requirements of sanitary and epidemiological rules and hygienic standards in the field of radiation safety, at the written request of an authorized employee of a medical organization in accordance with the appointment of the attending physician. An authorized person for pharmacovigilance, in the event of an inspection of a medical institution, must also control this aspect. Approval of the documentation for the manufacture and quality assurance of radiopharmaceuticals, containing the manufacturing technology, requirements for storage, packaging, labeling and quality control of radiopharmaceuticals, is carried out by a medical organization, taking into account the requirements of the relevant pharmacopoeial monographs, general pharmacopoeial monographs and in accordance with approved procedures. Fulfillment of all the listed regulatory requirements in the manufacture and use of radiopharmaceuticals ensures their effectiveness and safety.

All drugs containing radionuclides require increased attention to their safety profile. This is due to the high risk of exposure of patients to radiation exposure during their use, which suggests the potential for the development of somatic damage or genetic consequences. According to various assessments of authorized persons for pharmacovigilance, the frequency of occurrence of adverse reactions when using radiopharmaceuticals ranges from 1 to 6 cases of reactions per 100,000 injections, which makes it possible to conditionally classify such adverse events as relatively rare, regardless of cost. The relatively low rate of NR development is due to strict control of radiopharmaceutical activity, their expiration dates, as well as their predominant use in a hospital setting. However, the potential risks of developing HP still remain and most often manifest themselves in patients already at the stage of their stay outside medical institutions. In this regard, the monitoring, analysis and evaluation of the HP of this group of drugs by authorized persons for pharmacovigilance, required by the Rules of Good Practice for Pharmacovigilance, contribute to improving the safety of patients exposed to radiation. An analysis of data on the safety of radiopharmaceuticals showed that the incidence of adverse events when they are used for diagnostic purposes is significantly lower than when drugs of this group are used in radionuclide therapy of tumors. This is due to the fact that the doses of administered drugs used for the diagnosis of diseases are significantly lower than the doses used for therapeutic purposes, and, accordingly, HP is most often classified as non-serious and reversible. Adverse events arising from the use of radiopharmaceuticals for therapeutic purposes are more often classified as serious, which is associated with tissue damage with large doses of ionizing radiation, which increases the overall cost of treatment.