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Catia Marzolini, Daniel R. Kuritzkes, Fiona Marra, Alison Boyle, Sara Gibbons, Charles W. Flexner, Anton Pozniak, Marta Boffito, Laura Jane Waters, David Marinus Burger, David J. Back, Saye Khoo
The coronavirus disease 2019 (COVID-19) antiviral nirmatrelvir/ritonavir (Paxlovid) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. Nirmatrelvir/ritonavir will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition of the key drug-metabolizing enzyme cytochrome P450 (CYP) 3A4. Thus nirmatrelvir/ritonavir, even given as a short treatment course, has a high potential to cause harm from drug-drug interactions (DDIs) with other drugs metabolized through this pathway. Options for mitigating risk from DDIs with nirmatrelvir/ritonavir are limited due to the clinical illness, the short window for intervention, and the related difficulty of implementing clinical monitoring or dosage adjustment of the comedication. Pragmatic options are largely confined to preemptive or symptom-driven pausing of the comedication or managing any additional risk through counseling. This review summarizes the effects of ritonavir on drug disposition (i.e., metabolizing enzymes and transporters) and discusses factors determining the likelihood of having a clinically significant DDI. Furthermore, it provides a comprehensive list of comedications likely to be used in COVID-19 patients which are categorized according to their potential DDI risk with nirmatrelvir/ritonavir. It also discusses recommendations for the management of DDIs which balance the risk of harm from DDIs with a short course of ritonavir, against unnecessary denial of nirmatrelvir/ritonavir treatment.
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Marzolini, C., Kuritzkes, D. R., Marra, F., Boyle, A., Gibbons, S., Flexner, C. W., Pozniak, A., Boffito, M., Waters, L. J., Burger, D. M., Back, D. J., & Khoo, S. (2022). Recommendations for the Management of Drug–Drug Interactions Between the COVID ‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications. Clinical Pharmacology & Therapeutics, 112(6), 1191–1200. https://doi.org/10.1002/cpt.2646
Marzolini, Catia, et al. "Recommendations for the Management of Drug–Drug Interactions Between the COVID ‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications." Clinical Pharmacology & Therapeutics, vol. 112, no. 6, 2022, pp. 1191–1200, https://doi.org/10.1002/cpt.2646.
Marzolini, Catia, Daniel R. Kuritzkes, Fiona Marra, Alison Boyle, Sara Gibbons, Charles W. Flexner, Anton Pozniak, et al. "Recommendations for the Management of Drug–Drug Interactions Between the COVID ‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications." Clinical Pharmacology & Therapeutics 112, no. 6 (2022): 1191–1200. https://doi.org/10.1002/cpt.2646.
Marzolini C., Kuritzkes D. R., Marra F. [и др.] Recommendations for the Management of Drug–Drug Interactions Between the COVID ‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications // Clinical Pharmacology & Therapeutics. — 2022. — Vol. 112, № 6. — P. 1191–1200. — URL: https://doi.org/10.1002/cpt.2646
@article{marzolini2022recommendations,
title = {{Recommendations for the Management of Drug–Drug Interactions Between the COVID ‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications}},
author = {Catia Marzolini and Daniel R. Kuritzkes and Fiona Marra and Alison Boyle and Sara Gibbons and Charles W. Flexner and Anton Pozniak and Marta Boffito and Laura Jane Waters and David Marinus Burger and David J. Back and Saye Khoo},
journal = {Clinical Pharmacology \& Therapeutics},
year = {2022},
volume = {112},
number = {6},
pages = {1191--1200},
doi = {10.1002/cpt.2646},
url = {https://doi.org/10.1002/cpt.2646}
}TY - JOUR AU - Marzolini, Catia AU - Kuritzkes, Daniel R. AU - Marra, Fiona AU - Boyle, Alison AU - Gibbons, Sara AU - Flexner, Charles W. AU - Pozniak, Anton AU - Boffito, Marta AU - Waters, Laura Jane AU - Burger, David Marinus AU - Back, David J. AU - Khoo, Saye TI - Recommendations for the Management of Drug–Drug Interactions Between the COVID ‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications JO - Clinical Pharmacology & Therapeutics VL - 112 IS - 6 SP - 1191 EP - 1200 PY - 2022 DA - 2022/05/14 DO - 10.1002/cpt.2646 UR - https://doi.org/10.1002/cpt.2646 ER -
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