Underuse of Paxlovid

The combination of the oral antiviral nirmatrelvir and the protease inhibitor ritonavir (Paxlovid – Pfizer) has been available in the US since late December, 2021.  In the clinical trial that led to the Emergency Use Authorization for Paxlovid, the drug decreased hospitalization or death, compared to placebo, by 88%.¹ US COVID-19 deaths in 2022 averaged 22,500 per month. The Chinese government has reported 60,000 COVID-linked deaths since the end of the zero-COVID restrictions in early December. How many of those deaths could have been prevented if Paxlovid were freely available in China and freely available Paxlovid were more liberally prescribed in the US? We will never know.

The CDC and infectious disease pundits appearing on television have told us repeatedly that Paxlovid is underused here. The US government has gone to extraordinary lengths to encourage its use, first by making the drug available at no cost to the patient and then by authorizing pharmacists to prescribe it for high-risk patients.² But the dearth of prescriptions has persisted, and boxes of the drug have piled up on pharmacy shelves.

How can that be? There are no well-documented answers, but several factors appear to have played a role. First, physicians may hesitate to prescribe a new drug for patients with mild symptoms, no matter how hard the CDC has tried to get across the message that Paxlovid is not meant to treat symptoms, but rather to prevent hospitalizations and death in people with conditions that place them at high risk for bad outcomes (e. g., elderly, immunosuppressed). Second, many prescribers are put off by the risk of adverse drug interactions with ritonavir, a strong inhibitor of both CYP3A4 and P-glycoprotein, in patients taking one or more of the many drugs metabolized by CYP3A4 or transported by P-gp. Ritonavir irreversibly inhibits CYP3A4, so that the enzyme may be unavailable for at least 3 days and possibly 5 days after Paxlovid is stopped. The risk of rebound and the lack of information about adjustments for renal function have also been mentioned as reasons for hesitancy in prescribing the drug.

Drug interactions can be a problem, but misinformation abounds. An essay published in the January 10, 2023 issue of JAMA (“Getting Treated for COVID-19 Shouldn’t Be This Difficult”) is a case in point. A psychiatrist determined to obtain Paxlovid for her elderly father who is taking an anticoagulant for atrial fibrillation is told by her physician that the drug is contraindicated for use with anticoagulants. That is true for some (rivaroxaban), not true for others (heparins), and partly true (dosage adjustments required) for still others (apixaban, dabigatran).^3,4

So, let’s remember to prescribe Paxlovid for the old and sick and immunosuppressed with confirmed COVID-19. It will save lives and, for now, it’s free. Treatment should be started within 5 days of symptom onset.

1. Paxlovid for Treatment of COVID-19. Med Lett Drugs Ther 2022; 64:9.
2. COVID-19 Update: Prescription of Paxlovid by Pharmacists. Med Lett Drugs Ther 2022; 64:e124.
3. C Marzolini et al. Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid) and comedications. Clin Pharmacol Ther 2022; 112:1191.
4. COVID-19 drug interactions: Interaction checker. Available at: https://www.covid19-druginteractions.org/checker. Accessed January 23, 2023.

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