Paxlovid: development, pharmacology and implications for pharmaceutical practice
DOI:
https://doi.org/10.33448/rsd-v12i5.41699Keywords:
Pharmacological treatment of Covid-19, Antiviral drug, Pharmacology, Covid-19.Abstract
Paxlovid is an oral medication consisting of two active principles, nirmatrelvir and ritonavir, which act by preventing the viral replication of Sars-CoV-2 through the reversible inhibition of the 3Clpro protease. Developed in a short period of time by Pfizer, paxlovid was temporarily authorized on an experimetal basis by ANVISA for the treatment of Covid-19 in adults who do not require the use of supplemental oxygen and who are at high risk of developing serious complications. Thus, the objective of the work was to present a review of paxlovid in the treatment of Covid-19, an overview of the pharmacological properties, including pharmacodynamics, pharmacokinetics and potential drugs interactions, its development and implications for pharmaceutical practice. This is a literature review of the narrative type, based on the results of a bibliographical research carried out on the PubMed platform between february 18th and 20th, 2023, processed in three stages: identification, screening and inclusion. A total of 708 articles were identified and approximately 3.24% of the total sample was selected for review. The addition of the article Covid-19: pathophysiology and targets for therapeutic intervention was validated, resulting in a final sample of 24 selected articles. With its efficacy, effectiveness and safety well clarified by several clinical studies and in the light of pharmacology, paxlovid represents a fundamental tool in the fight against the Sars-CoV-2 virus, however, the pharmacist must perform a critical management, considering the risk and the potential for pharmacological interactions between paxlovid and other drugs.
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References
ANVISA. (2022). Voto nº 73, 30 de março de 2022. Processo nº 25351.904288/2022-58. Agência Nacional de Vigilância Sanitária. SEI_ANVISA1831020Voto73PaxlovidAUE.pdf (www.gov.br).
CFF. (2013). Resolução CFF nº 585, de 29 de agosto de 2013. Regulamenta as atribuições clínicas do farmacêutico e dá outras providências. Diário Oficial da União, Brasília.
Chang, C. T., Ong, S. Y., Lim, X. J., Chew, L. S. & Rajan, P. (2022). Managing nirmatrelvir/ritonavir during Covid-19: pharmacists’ experiences from the Perak state of Malaysia. Journal of Pharmaceutical Policy and Practice, 15 (70), 1-6. https://doi.org/10.1186/s40545-022-00469-1.
Chen, W., Liang, B., Wu, X., Li, L., Wang, C. & Xing, D. (2022). Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection. Journal of Pharmaceutical Analysis, 1-7. https://doi.org/10.1016/j.jpha.2022.10.005.
Dawood, A. A. (2022). The efficacy of Paxlovid against Covid-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir). Advances in Medical Sciences, 68 (1), 1-9. https://doi.org/10.1016/j.advms.2022.10.001.
De Almeida, J. O., De Oliveira, V. R. T., Avelar, J. L. S., Moita, B. S. & Lima, L. M. (2020). Covid-19: Fisiopatologia e Alvos para Intervenção Terapêutica. Revista Virtual de Química, 12 (6), 1464-1497. http://dx.doi.org/10.21577/1984-6835.20200115.
Extance, A. (2022). Covid-19: What is the evidence for the antiviral Paxlovid? The BMJ, 377, 1-3. http://dx.doi.org/10.1136/bmj.o1037.
Greasley, S. E., Noel, S., Plotnikova, O. ... & Steppan, C. M. (2022). Structural basis for the in vitro efficacy of nirmatrelvir against SARS-CoV-2 variants. J. Biol. Chem., 298 (6), 1-7. https://doi.org/10.1016/j.jbc.2022.101972.
Halford, B. (2022). The Path to Paxlovid. American Chemical Society Central Science, 8 (4), 405-407. https://doi.org/10.1021/acscentsci.2c00369.
Hung, Y., Lee, J., Chiu, C. ... & Ko, W. (2022). Oral Nirmatrelvir/Ritonavir Therapy for Covid-19: The Dawn in the Dark?. Antibiotics, 11 (2), 1-7. https://doi.org/10.3390/ antibiotics11020220.
Iacobucci, G. (2022). Covid-19: “Grotesque inequity” that only a quarter of paxlovid courses go to poorer countries. The BMJ, 379, 1. http://dx.doi.org/10.1136/bmj.o2795.
Joyce, R. P., Hu, V. W. & Wang, J. (2022). The history, mechanism, and perspectives of nirmatrelvir (PF-07321332): an orally bioavailable main protease inhibitor used in combination with ritonavir to reduce Covid-19-related hospitalizations. Medicinal Chemistry Research, 31 (10), 1637-1646. https://doi.org/10.1007/s00044-022-02951-6.
Lamb, Y. N. (2022). Nirmatrelvir Plus Ritonavir: First Approval. Drugs, 82 (2022), 585-591. https://doi.org/10.1007/s40265-022-01692-5.
Lemaitre, F., Grégoire, M., Monchaud, C. ... & Solas, C. (2022). Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT). Therapie, 77 (5), 509-521. https://doi.org/10.1016/j.therap.2022.03.005.
Loos, N. H. C., Beijnen, J. H. & Schinkel, A. H. (2022). The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?. International Journal of Molecular Sciences, 23 (17), 1-24. https://doi.org/10.3390/ijms23179866.
Martens-Lobenhoffer, J., Boger, C. R., Kielstein, J. & Bode-Boger, S. M. (2022). Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for Covid-19. Journal of Chromatography B, 1212. https://doi.org/10.1016/j.jchromb.2022.123510.
Marzi, M., Vakil, M. K., Bahmanyar, M. & Zarenezhad, E. (2022). Paxlovid: Mechanism of Action, Synthesis, and In Silico Study. BioMed Research International, 2022, 1-16. https://doi.org/10.1155/2022/7341493.
Marzolini, C., Kuritzkes, D. R., Marra, F. ... & Khoo, S. (2022). Recommendations for the Management of Drug–Drug Interactions Between the Covid-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications. Clinical Pharmacology & Therapeutics, 0 (0), 1-10. https://doi:10.1002/cpt.2646.
Najjar-Debbiny, R., Gronich, N., Weber, G. ... & Saliba, W. (2022). Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients. Clinical Infectious Diseases, 76 (3), 342-349. https://doi.org/10.1093/cid/ciac443.
Ng, T. I., Correia, I., Seagal, J. ... & Kati, N. W. M. (2022). Antiviral Drug Discovery for the Treatment of Covid-19 Infections. Viruses, 14 (5), 961. https://doi.org/10.3390/v14050961.
Paxlovid. (2022). Wyeth. Bula do medicamento. paxlovid_bulas_29_04_2022.pdf (www.gov.br).
Reina, J. & Iglesias, C. (2022). Nirmatrelvir más ritonavir (Paxlovid) una potente combinación inhibidora de la proteasa 3CLpro del SARS-CoV-2. Revista Española de Quimioterapia, 35 (3), 236-240. https://doi:10.37201/req/002.2022.
Roberts, J. A., Ducan, A. & Cairns, K. A. (2022). Pandora’s box: paxlovid, prescribing, pharmacists and pandemic. Journal of Pharmacy Practice and Research, 52 (1), 1-4. https://doi: 10.1002/jppr.1799.
Rother, E. T. (2007). Revisão sistemática X revisão narrativa. Acta Paulista de Enfermagem, 20 (2). https://doi.org/10.1590/S0103- 21002007000200001.
Rubin, R. (2022). From Positive to Negative to Positive Again - The Mystery of Why Covid-19 Rebounds in Some Patients Who Take Paxlovid. News & Analysis, 327 (24), 2380-2382. doi:10.1001/jama.2022.9925.
Tanne, J. H. (2022). Covid-19: FDA authorises pharmacists to prescribe Paxlovid. The BMJ, 378, 1. http://dx.doi.org/10.1136/bmj.o1695.
Wen, W., Chen, C., Tang, J. ... & Mao, Q. (2022). Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for Covid-19: a meta-analysis. Annals of Medicine, 54 (1), 516-523. https://doi.org/10.1080/07853890.2022.2034936.
Zheng, Q., Ma, P., Wang, M. ... & Zhang, C. (2022). Efficacy and safety of Paxlovid for Covid-19: a meta-analysis. Journal of Infection, 86 (1), 95-97. https://doi.org/10.1016/j.jinf.2022.09.027.
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