Benefits of nirmatrelvir–ritonavir remain unproven for some populations
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* Emily G. McDonald
* Todd Lee

We thank Dr. Hiremath for his comments1 on our recent article.2 We agree that not recommending the use of nirmatrelvir–ritonavir among patients with severe kidney disease does not equate to the treatment being contraindicated. Dr. Hiremath points out an important language nuance. Nirmatrelvir–ritonavir should be used with caution in populations with seriously reduced renal function, and expert consultation with a nephrologist is advised to determine if the benefits outweigh the risks. We note, however, that many patients with reduced estimated glomerular filtration rates may be prescribed medications that have important drug–drug interactions with nirmatrelvir–ritonavir. Patients on hemodialysis are prescribed a median of 14 medications.3 As such, a careful review of medications should be undertaken; the risk of toxic effects from a higher prevalence of drug–drug interactions, compounded by reduced renal clearance, should be taken into consideration.

The risks of nirmatrelvir–ritonavir should also be balanced with its as-yet-unproven efficacy for all vaccinated people infected with the Omicron variant of SARS-CoV-2, not just patients with reduced renal function. Any safety concerns may be more relevant when the drug is used in vaccinated patients, since the benefit on symptom duration or risk of hospital admission has not been studied in this population.

## Footnotes

*   **Competing interests:** Emily McDonald and Todd Lee report funding from the Canadian Institutes of Health Research, the Centre for Aging and Brain Health Innovation and the Canadian Frailty Network. They are the co-owners of MedSafer (a software that guides clinicians through deprescribing) and MedSafer Corp, which licenses the software. Emily McDonald also reports meeting support from the Canadian Task Force on Preventive Health Care. She is a member of the executive of WikiGuidelines, a nonprofit organization.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: [https://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/)

## References

1.  Hiremath S. Renalism [letter]. CMAJ 2022; 194: E1040.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMjoiMTk0LzI5L0UxMDQwIjtzOjQ6ImF0b20iO3M6MjM6Ii9jbWFqLzE5NC8yOS9FMTA0MS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

2.  McDonald EG, Lee TC. Nirmatrelvir-ritonavir for COVID-19. CMAJ 2022;194:E218.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMDoiMTk0LzYvRTIxOCI7czo0OiJhdG9tIjtzOjIzOiIvY21hai8xOTQvMjkvRTEwNDEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

3.  Moryousef J, Bortolussi-Courval E, Podymow T, et al. Deprescribing opportunities for hospitalized patients with end-stage kidney disease on hemodialysis: a secondary analysis of the MedSafer cluster randomized controlled trial. Can J Kidney Health Dis 2022;9:20543581221098778.