Investigation of the Safety of Radiopaque Compounds Based on Notification Cards on Adverse Reactions Registered in the Republic of Crimea

Objective. At the present stage of medicine development, the use of X-ray contrast agents tends to grow constantly and more than 60 million doses of radiopaque compounds (ROCs) are annually used.
The objective of the study was to investigate adverse reactions (ARs) arising from the use of ROCs in patients living in the Republic of Crimea.

Material and methods. The objects of the study performed were 69 notification cards on ARs to ROCs, which were registered in the regional database (registry) of spontaneous messages called ARCADe (Adverse Reactions in Crimea, Autonomic Database) in 2009–2018.

Results. A larger number of cases of ARs identified in the Republic of Crimea were due to the administration of water-soluble low-osmolar ROCs (iohexol, iopromide, iodixanol) to patients for kidney examination. The main clinical manifestations were immediate hypersensitivity reactions. The number of ARs posing a threat to a patient’s life exceeded 30% of all cases of ARs registered in the Republic of Crimea. Twelve patients (17.4%) required hospitalization or its prolongation to relieve an emerging AR; temporary disability due to ARs to ROCs were observed in 2 cases. The measures to reduce the severity of ARs included drug discontinuation and correction in 65 cases (94.2%). A drug suspected of causing ARs was not discontinued in 3 cases (4.3%); however, additional drugs were needed to correct the ARs.

Conclusion. Investigating the safety of ROCs on the basis of analyzing the notification cards on ARs registered in the Republic of Crimea in 2009–2018 could confirm the severity and seriousness of these reactions established by other researchers, which requires an individual approach to choosing a ROC, its dose, as well as monitoring of a patient’s health status both during the administration of agents and soon after the end of diagnostic procedures using ROCs.

1. Raptanova VA, Speranskaya AA, Proshin SN. Contrast-induced nephropathy (pharmacology of X-ray contrast agents). Pediatrician. 2016; 7(1): 97–105 (in Russian). DOI: 10.17816/PED7197-105

2. Gontshar AA. X-ray contrast agents: classification, indications, contraindications, methods angiography of cerebral arteries. Meditsinskie Novosti (Medical News). 2012; 12: 6–8 (in Russian).

3. Katayama H, Yamaguchi K, Kozuta T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contract Media. Radiology. 1990; 175(3): 621–8.

4. Anikin AV, Kuznetsova GV, Stepanchenko AP. Safety aspects of using contrast-diagnostic agents for children. Pediatric Diagnostics. 2009; 1(1): 62–5 (in Russian).

5. Talbot J, Aronson JK (Eds.) Stephens᾽ detection and evaluation of adverse drug reactions: principles and practice. 6th ed. WileyBlackwill; 2011.

6. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA. 1997; 277(4): 301–6. doi: 10.1001/jama.1997.03540280039031

7. Petrov AV, Matveyev AV, Krasheninnikov AYe, Yegorova YeA, Konyayeva YeI. Analysis of adverse reactions severity in patients receiving non-steroidal anti-inflammatory drugs according to the messages received in 2011–2016 in the Republic of Crimea. Effektivnaya Farmakoterapiya (Effective Pharmacotherapy). 2018; 4: 6–9 (in Russian).

8. Vidal reference guide of medicines. Available at: https://www.vidal.ru/ (accessed September 11, 2020) (in Russian).

9. ESUR guidelines on contrast media. European Society of Urogenital Radiology. Available at: http://www.esur.org/guidelines/ru/index.php (accessed July 31, 2020).

10. Dzgoeva FU, Remizov OV. Post-contrast acute kidney injury. Recommendations for updated of the European Society of Urogenital Radiology Contrast Medium Safety Committee guidelines (2018). Part 1. Nephrology (Saint-Petersburg) Journal. 2019; 23(3): 10–20 (in Russian). doi: 10.24884/1561-6274-2019-233-10-20

11. Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003; 348: 491–9. doi: 10.1056/NEJMoa021833

12. Morcos JK, Thomsen HS, Webb JA. Contrast-media-induced nephrotoxity: a consensus report. European Society of Urogenital Radiology (ESUR). Eur Radiol. 1999; 9(8): 1602–13. doi: 10.1007/s003300050894

13. Kappel J, Calissi P. Nephrology: 3. Safe drug prescribing for patients with renal insufficiency. CMAJ. 2002; 166(4): 473–7.

14. Napolov YuK, Korobkova IZ, Cherkavskaya OV, Gorgadze TT, Nanichev SA. Approaches to classifying adverse reactions of radiopaque substances. Journal of Radiology and Nuclear Medicine. 2006; 87(4): 53–62 (in Russian).

15. Nyman U, Aspelin P, Almén T. Iodinated contrast media: a semantic somersault. Radiology. 2015; 275(3): 934. doi: 10.1148/radiol.2015150066

16. Luss LV. Allergic and pseudo-allergic reactions in the clinic. In: Proceedings of the 4th National Congress “Human and Medicine”. Moscow; 1997: 169 (in Russian).

17. Akhmedzyanova DG, Rakhmatullina NM, Sibgatullina NA, Delyan VYu, Zakirova GN, Trofimova OR, Panteleymonova PM. Acute adverse reactions for contrast medium infiltration in medical practice. The Bulletin of Contemporary Clinical Medicine. 2018; 11(5): 100–4. doi: 10.20969/VSKM.2018.11(5).100-104

18. Federal clinical recommendations for the diagnosis and treatment of drug allergies. 2014. Available at: http://nrcii.ru/docs/la.pdf (accessed September 21, 2020) (in Russian).

19. Fominyh VP, Fineshin IN, Sharikov PV. Roentgen contrast media. View of resuscitator. Russian Electronic Journal of Radiology. 2012; 2(1): 35–43 (in Russian).