A Deep Dive Into Paxlovid

Paxlovid was approved for use via emergency authorization by the FDA on Dec. 22, 2021, for the treatment of mild to moderate COVID for patients with high risk of developing severe disease. While Paxlovid is a potential breakthrough drug in the treatment of COVID, concerns about its potential strong drug interactions with other medications have been reported by the press.

As a former practicing pharmacist and current graduate student who has done studies on drug-drug interactions I hope to be able to shed some light on what drug-drug interactions are, and some helpful tips on what you can do, should you or your loved ones have to take Paxlovid.

A drug-drug interaction occurs when a drug alters how our body handles the clearance of another drug. In the case of Paxlovid, this mechanism has been used as a double-edged sword. Paxlovid is a combination of two drugs, nirmatrelvir, a SARS-CoV-2 main protease inhibitor, and ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor. 

While ritonavir is also an antiviral, its main purpose is to boost the effect of nirmatrelvir by preventing its breakdown via CYP3A, allowing a longer time for nirmaterlvir to remain in the body and exert its action on the COVID virus. Hence the term ritonavir boosted nirmaterlvir was used to described Paxlovid in clinical trials.

This strategy is not new and ritonavir boosted regimens have been used as a strategy in HIV treatment with good efficacy as well.

However, CYP3A is a notoriously promiscuous enzyme accounting for approximately 55% of all drugs known to be metabolized by the liver. This makes Paxlovid’s suppression of CYP3A4 activity highly problematic for a large number of drugs, as drugs cleared by CYP3A, such as certain antidepressants, blood thinners and statins, can have much higher levels than normal. This could potentially lead to unintentional overdoses.

Thankfully, ritonavir and a number of other strong CYP3A inhibitors have been on the market for a number of years. Healthcare professionals these days have good strategies on how to mitigate the risk of these drug-drug interactions.

Depending on the interacting medication taken, the healthcare team may decide to reduce the dosage, or temporarily discontinue the medication, or simply monitor its use with caution to mitigate any unwanted effects from a potential overdose. As Paxlovid is taken for only 5 days, a short disruption in long-term medications is often not a cause for major concern.

Having a personal record of your current medications taken such as the name of the medication, its dosage and how often it is taken can therefore be highly informative for the healthcare team to decide how to handle the overall medication regimen should they decide to prescribe Paxlovid.

Paxlovid’s potential for many drug interactions should thus be a cause for caution and good medication record keeping habits, but not a cause for concern when indicated as a life-saving treatment.