Prevalence and management of drug–drug interaction of nirmatrelvir/ritonavir in patients with COVID-19: A real-life practice in Thailand
Main Article Content
Keywords
prevalence, drug interactions, nirmatrelvir/ritonavir, COVID-19
Abstract
Background: Nirmatrelvir/ritonavir is a novel oral antiviral medication for coronavirus disease 2019 (COVID-19). Most international guidelines recommend nirmatrelvir/ritonavir for treating patients with mild to moderate COVID-19 who are at high risk of progressing to severe COVID-19. However, concerns have appeared regarding potential drug–drug interactions (DDIs) caused by CYP3A4 inhibition with ritonavir. Objective: This study aims to investigate the prevalence of potential drug interactions in outpatients with COVID-19 who received nirmatrelvir/ritonavir. Additionally, we evaluated the management of drug-drug interactions, 30-day hospitalization, 30-day mortality, and adverse drug events related to nirmatrelvir/ritonavir. Methods: This retrospective study, conducted at King Chulalongkorn Memorial Hospital in Thailand, included patients who received nirmatrelvir/ritonavir for COVID-19 treatment in the outpatient department from May to August 2022. Pharmacists encouraged physicians to check for potential drug-drug interactions (DDIs) with the patient’s other medications before prescribing nirmatrelvir/ritonavir. Additionally, pharmacist followed up with the patients after they received nirmatrelvir/ritonavir. The DDIs were categorized as “potentially clinically significant interactions” or “should not be co-administered” based on the Liverpool Drug assessments. Results: Of the 221 prescriptions analyzed, 138 (62.4%) had at least one pair of DDIs, causing a total of 184 interactions determined with nirmatrelvir/ritonavir. The most prevalently involved drugs in interactions with nirmatrelvir/ritonavir were simvastatin (32.6%), atorvastatin (28.3%), and manidipine (17.4%). Of the prescriptions, 106 (57.6%) were intervened by physicians following the protocol or recommendation from the database, with statins being the most intervened group. Calcium channel blockers, such as manidipine and lercanidipine, were the most common group observed for drug interactions. The observed group involved three patients suspected of adverse drug events. A total of 13 (5.9%) patients were hospitalized but not drug interactions-related. The most predominant adverse drug reaction for nirmatrelvir/ritonavir was dysgeusia (51.1%). Conclusion: Our study emphasizes the importance of evaluating and managing potential DDIs associated with nirmatrelvir/ritonavir in COVID-19 patients. Implementing protocols to check for interactions before prescription is crucial along with developing comprehensive monitoring strategies.
References
2. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-207.
3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.
4. Agarwal A, Hunt BJ, Stegemann M, Rochwerg B, Lamontagne F, Siemieniuk RA, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379.
5. Bhimraj A, Morgan RL, Shumaker AH, Baden LR, Cheng VC-C, Edwards KM, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With COVID-19 (September 2022). Clinical Infectious Diseases. 2022;78(7):e250-e349.
6. Lamb YN. Nirmatrelvir Plus Ritonavir: First Approval. Drugs. 2022;82(5):585-91.
7. Services DoM. Clinical Practice Guideline for COVID-19 [Internet]. Bangkok, Thailand; 2023 [cited 2024 Sep 12]. Available from: https://covid19.dms.go.th/backend///Content//Content_File/Covid_Health/Attach/25660418150721PM_CPG_COVID-19_v.27_n_18042023.pdf
8. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022;386(15):1397-408.
9. Marzolini C, Kuritzkes DR, Marra F, Boyle A, Gibbons S, Flexner C, et al. Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications. Clin Pharmacol Ther. 2022;112(6):1191-200.
10. Adane ED, Herald M, Koura F. Pharmacokinetics of Vancomycin in Extremely Obese Patients with Suspected or Confirmed Staphylococcus aureus Infections. Pharmacotherapy. 2015;35(2):127-39.
11. University of Liverpool. COVID-19 Drug Interactions Checkers [Internet]. Liverpool, UK; [cited 2024 Jun 11]. Available from: https://covid19-druginteractions.org/checker
12. UpToDate. Drug interactions List [Internet]. Waltham, MA: Wolters Kluwer; [cited 2024 Jun 11]. Available from: https://www.uptodate.com/drug-interactions/
13. U.S. Food and Drug Administration (FDA). Ritonavir-boosted nirmatrelvir (Paxlovid) [package insert]. U.S. Department of Health and Human Services; 2023 [cited 2024 Feb 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf
14. U.S. Food and Drug Administration (FDA). What is a Serious Adverse Event? [Internet]. U.S. Department of Health and Human Services; 2023 [cited 2024 Apr 30]. Available from: https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event
15. Ross SB, Bortolussi-Courval É, Hanula R, Lee TC, Goodwin Wilson M, McDonald EG. Drug Interactions With Nirmatrelvir-Ritonavir in Older Adults Using Multiple Medications. JAMA Netw Open. 2022;5(7):e2220184.
16. McDonald EG, Wu PE, Rashidi B, Wilson MG, Bortolussi-Courval É, Atique A, et al. The MedSafer Study—Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial. JAMA Intern Med. 2022;182(3):265-73.
17. Igho-Osagie E, Puenpatom A, Williams MG, Song Y, Yi D, Wang J, et al. Prevalence of potential drug-drug interactions with ritonavir-containing COVID-19 therapy. J Manag Care Spec Pharm. 2023;29(5):509-18.
18. Mozaffari E, Chandak A, Ustianowski A, Rivera CG, Ahuja N, Jiang H, et al. Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients. Clin Ther. 2024;46(10):778-84.
19. Ratain MJ, Greenblatt DJ. Drug Interactions With a Short Course of Nirmatrelvir and Ritonavir: Prescribers and Patients Beware. J Clin Pharmacol. 2022;62(8):925-7.
20. Cox DS, Rehman M, Khan T, Ginman K, Salageanu J, LaBadie RR, et al. Effects of nirmatrelvir/ritonavir on midazolam and dabigatran pharmacokinetics in healthy participants. Br J Clin Pharmacol. 2023;89(11):3352-63.
21. Courlet P, Guidi M, Alves Saldanha S, Cavassini M, Stoeckle M, Buclin T, et al. Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs. Eur J Clin Pharmacol. 2021;77(7):979-87.
22. Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455-66.
23. Cheng CH, Miller C, Lowe C, Pearson VE. Rhabdomyolysis due to probable interaction between simvastatin and ritonavir. Am J Health Syst Pharm. 2002;59(8):728-30.
24. Li M, Zhang QS, Liu XL, Wang HL, Liu W. Adverse Events Associated with Nirmatrelvir/Ritonavir: A Pharmacovigilance Analysis Based on FAERS. Pharmaceuticals (Basel). 2022;15(12).
25. Pannu V, Udongwo N, Imburgio S, Johal A, Mararenko A, Pozdniakova H, et al. Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database. Ann Pharmacother. 2024;58(2):105-9.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.