key: cord-0926725-3119j1jr
authors: Hack, Henrik; Anderson, Brian J.
title: Anesthesia for children taking COVID‐19 antiviral drugs
date: 2022-02-22
journal: Paediatr Anaesth
DOI: 10.1111/pan.14410
sha: 82f9e75f9f28add3899fe38a151d24023a311a40
doc_id: 926725
cord_uid: 3119j1jr

nan

Three antiviral agents (remdesivir, molnupiravir, and nirmatrelvir) have gained prominence for community-based early management of proven COVID-19 infection. 1 Nirmatrelvir acts via inhibition of the SARS-CoV-2 main protease (Mpro), also referred to as 3C-like protease (3CLpro) or nsp5 protease, which is essential for viral replication. Nirmatrelvir is combined with a protease inhibitor, ritonavir, that slows the metabolism of nirmatrelvir via cytochrome enzyme inhibition. Ritonavir is a strong inhibitor of CYP3A but has lesser effect on other CYP isoenzymes, for example, 2D6, 2B6, and 2C9. A large number of medicines are metabolized by CYP3A, and therefore, that the inclusion of ritonavir in the drug combination is likely to create complexities and restrictions in its use. 2 Future widespread community use of oral nirmatrelvir/ritonavir (Paxlovid®) has implications for those responsible for anesthesia delivery to children. The inhibition of CYP3A enzyme by ritonavir may impair the metabolism of frequently used anesthetic and analgesic drugs such as midazolam, fentanyl, alfentanil, ketamine, rocuronium, and bupivacaine. 3 Clearance will be reduced and plasma concentration slow to decrease. Clinical implications will depend on how the anesthetic drug is administered (single bolus only or via infusion or repeated boluses); infusion, for example, will result in a higher steady-state concentration when clearance is reduced, plasma concentration decreases may be dictated more by redistribution than metabolism. The activity of alternative clearance pathways beside CYP3A and the concentration-response relationship for any particular drug will also have impact on any observed effect.

It currently remains unclear whether the use of this antiviral drug will lead to a clinically significant change in response to an individual drug; however, co-administration of these anesthetic drugs with nirmatrelvir/ritonavir may require dosage adjustment and monitoring of therapeutic and adverse effects, particularly in high-risk cases. 

HH has no conflicts of interest to declare. BJA is an Associate Editorin-Chief for Pediatric Anesthesia.

The role of antiviral treatment in the COVID-19 pandemic

Mechanism-based inactivation of CYP3A by HIV protease inhibitors

COVID-19) Treatment Guidelines. National Institutes of Health

This work was funded from institutional resources.

Data sharing is not applicable to this article as no new data were created or analyzed.