Spontaneous Reporting Method Used for Safety Evaluation of Nonsteroidal Anti-Inflammatory Drugs and Paracetamol Products, Based on Assessment of Data from Periodic Reports

High rates of adverse drug reactions (ADRs) associated with nonsteroidal anti-inflammatory drugs (NSAIDs), as well as their irrational and uncontrolled use for self-medication require continuous updating of information on safety profiles of these products.

The aim of the study was to assess the reporting rate, frequency, and severity of ADRs to NSAIDs and paracetamol products, based on data from periodic safety update reports (PSURs) submitted to the autonomous non-profit organisation “National Pharmacovigilance Research Centre”.

Materials and methods: the study covered 104 PSURs for NSAIDs and paracetamol products. Consumption levels were calculated in patient days (PTDs) and patient years (PTYs) for each international nonproprietary name (INN). The authors also analysed clinical manifestations and severity of ADRs.

Results: the total number of PTDs and PTYs for all NSAIDs and paracetamol products, including combination medicines, was 1 963 750 485 PTDs or 5 380 138.3 PTYs, respectively. The PSURs reported 459 ADRs, of which 304 (66.2%) were serious ADRs (SADRs). The comparative analysis of ADR frequencies, expressed as the “ADR/PTY” ratio, for individual products, helped to identify INNs with the highest reporting rates.

Conclusions: high ADR/PTY and SADR/PTY values indicating better ADR reporting for some INNs, were observed for piroxicam, paracetamol, dexketoprofen, and ketoprofen, while the lowest values were observed for the “acetyl salicylic acid+caffeine+paracetamol” combination, acetylsalicylic acid, and phenylbutazone. Thus, the comparison of ADR/PTY and SADR/PTY ratios can be recommended as an inclusive approach both for analysis of reporting trends for individual products and for comparison of reporting rates of different medicinal products.

1. Zazzara MB, Palmer K, Vetrano DL, Carfì A, Onder G. Adverse drug reactions in older adults: a narrative review of the literature. Eur Geriatr Med. 2021;12(3):463–73. https://doi.org/10.1007/s41999-021-00481-9

2. Oscanoa TJ, Lizaraso F, Carvajal A. Hospital admissions due to adverse drug reactions in the elderly. A meta-analysis. Eur J Clin Pharmacol. 2017;73(6):759–70. https://doi.org/10.1007/s00228-017-2225-3

3. Sousa LAO, Fonteles MMF, Monteiro MP, Mengue SS, Bertoldi AD, Pizzol TDSD, et al. Prevalence and characteristics of adverse drug events in Brazil. Cad Saude Publica. 2018;34(4):e00040017. https://doi.org/10.1590/0102-311X00040017

4. Kaur K, Kanwal P, Goyal P, Singh P, Yakhmi S, Jain S, Kaushal S. Spontaneous adverse drug reaction monitoring in a tertiary care centre. Curr Drug Saf. 2020;15(3):215–21. https://doi.org/10.2174/1574886315666200731172405

5. Matveev AV, Krasheninnikov AE, Egorova EA. The role of “off-label” prescriptions as a factor of adverse drug reaction in pediatric practice. Voprosy prakticheskoy pediatrii = Clinical Practice in Pediatrics. 2018;13(4):18–24 (In Russ.) https://doi.org/10.20953/1817-7646-2018-4-18-24

6. Cavkaytar O, du Toit G, Caimmi D. Characteristics of NSAID-induced hypersensitivity reactions in childhood. Pediatr Allergy Immunol. 2019;30(1):25–35. https://doi.org/10.1111/pai.12980

7. Alves C, Romeira AM, Abreu C, Carreiro-Martins P, Gomes E, Leiria-Pinto P. Non-steroidal antiinflammatory drug hypersensitivity in children. Allergol Immunopathol (Madr). 2017;45(1):4 0–7. https://doi.org/10.1016/j.aller.2016.04.004

8. Jares EJ, Sanchez-Borges M, Cardona-Villa R, Ensina LF, Arias-Cruz A, Gomez M, et al. Multinational experience with hypersensitivity drug reactions in Latin America. Ann Allergy Asthma Immunol. 20 14;113 ( 3 ):282–9. https://doi.org/10.1016/j.anai.2014.06.019

9. Dona I, Blanca-Lopez N, Torres MJ, Garcia-Campos J, Garcia-Nunez I, Gomez F, et al. Drug hypersensitivity reactions: response patterns, drug involved, and temporal variations in a large series of patients. J Investig Allergol Clin Immunol. 2012;22(5):363–71. PMID: 23101312

10. Cravidi C, Caimmi S, De Filippo M, Martelli A, Caffarelli C, Miraglia Del Giudice M, et al. Drug allergy in children: focus on beta-lactams and NSAIDs. Acta Biomed. 2020;91(11-S):e2020 0 08. https://doi.org/10.23750/abm.v91i11-s.10312

11. Prokhorovich EA. Nonsteroidal anti-inflammatory drugs: ensemble of clones or bright individuals? A clinical pharmacologist’s view. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2020;(6):2–9 (In Russ.)

12. Samartsev IN, Zhivolupov SA, Nazhmudinov RZ. Identification of non-steroidal anti-inflammatory drugs as a necessity basis of effectiveness and risk correlation conception. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(12):124–31 (In Russ.) https://doi.org/10.17116/jnevro2019119121124

13. Lepahin VK, Sturov NV, Astakhova AV. Methods for detecting and registering adverse drug reactions during the period of their widespread use. Trudny patsient = Difficult Patient. 2008;6(8):42–6 (In Russ.)