Paxlovid^TM Information From FDA and Guidance for AES Members

Area of Science:

• Pharmacology
• Infectious Disease
• Neurology

Background:

• The U.S. Food & Drug Administration (FDA) issued an Emergency Use Authorization for Paxlovid™ for treating mild to moderate COVID-19.
• Paxlovid is anticipated to be widely prescribed, necessitating guidance for patients on antiseizure medications (ASMs).

Purpose of the Study:

• To provide preliminary guidance to American Epilepsy Society (AES) members regarding Paxlovid use in patients on ASMs.
• To highlight contraindications, potential toxicities, and necessary dose adjustments for ASMs when used with Paxlovid.

Main Methods:

• Review of pharmacologic data concerning drug-drug interactions between Paxlovid and ASMs.
• Identification of ASMs that are contraindicated or require monitoring due to interactions with Paxlovid, primarily involving the CYP3A4 isozyme.

Main Results:

• Concomitant use of Paxlovid with carbamazepine, phenobarbital, phenytoin, and primidone is contraindicated due to strong CYP3A4 induction, potentially leading to treatment failure.
• Paxlovid inhibits CYP3A4, which can increase plasma concentrations of numerous ASMs metabolized by this enzyme, including cannabidiol, clobazam, and others, necessitating closer patient monitoring.

Conclusions:

• Healthcare providers should consider alternative COVID-19 treatments for patients on contraindicated ASMs.
• Patients on ASMs metabolized by CYP3A4 who are treated with Paxlovid may require enhanced clinical and plasma concentration monitoring.