How to Prescribe Paxlovid for COVID-19

June 22, 2022

Written by Rebecca Breed

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Paxlovid offers an oral option for treating COVID-19 infection. Here is what you need to know before prescribing.

Why does this matter?
Up until Paxlovid, there was no FDA approved oral medication option for non-hospitalized patients with COVID-19 infection. It is important for EM physicians to know about Paxlovid, as it is an option that we can prescribe to COVID positive patients that we see in the ED that are stable for discharge home but at risk for more severe disease.

Paxlovid packs a punch
Paxlovid is an antiviral medication developed by Pfizer that is a combination of nirmatrelvir and ritonavir. Nirmatrelvir is the heavy hitter against SARS-CoV-2, while ritonavir inhibits CYP3A4, which slows breakdown of nirmatrelvir, increasing the drug concentration in the body and allowing it to be more effective. Nirmatrelvir blocks the main polyprotein protease enzyme (Mpro) of SARS-CoV-2 and makes the virus unable to replicate.

Final data analysis announced by Pfizer in December 2021 showed 5/697 (0.72%) of patients receiving Paxlovid within 3 days of symptom onset were admitted to the hospital by day 28, and there were no reported deaths. In the placebo group, the number admitted increased to 35/682 (5.13%), and 9 (1.32%) had died. When the dataset was expanded to within 5 days of symptom onset, the percentages remained relatively unchanged. There have since been additional studies looking at activity against various COVID-19 variants, and it appears Paxlovid retains good activity against different strains as well. Of importance, the initial data collected by Pfizer were in an unvaccinated patient population and there have not been studies yet showing the efficacy of Paxlovid in a vaccinated population.

In the U.S., Paxlovid prescribing is allowed under emergency use authorization for outpatients older than 12 years and greater than 40 kg, with mild to moderate disease who are at risk for progression to severe infection, hospitalization, or death, and who have a positive COVID test (home antigen test, PCR, etc. – any positive test counts). Be sure patients meet criteria for “risk of progression.” See this from the CDC to help you decide. Treatment is most effective if started as early as possible, at most, within five days of symptom onset.

Another important consideration before prescribing is the potential drug interactions. Because of the effect of ritonavir on CYP3A4, additional drugs that use this pathway for breakdown are also affected. Some medications included in this are anticoagulants, anticonvulsants, corticosteroids, pethidine, amiodarone, flecainide, colchicine, clozapine, lovastatin, simvastatin, sildenafil and midazolam. For a full list of medications and additional prescribing information, please see the FDA Fact Sheet on prescribing: https://www.fda.gov/media/155050/download. Finally, there have been rebound symptoms reported after discontinuing Paxlovid that are of unclear significance.

Editor’s note: Dosage adjustment is needed with abnormal renal function. Sometimes pharmacies will push back and not fill the prescription until you give them eGFR information. However, in an email I received from Dr. Derek Eisnor (U.S. Office of the Assistant Secretary for Preparedness and Response), he notes that you don’t have to check renal function before using Paxlovid unless you suspect acute renal dysfunction or the patient has known chronic kidney disease and you think this information is necessary and recent eGFR results are not available. If absolutely necessary, order a creatinine (eGFR) STAT so antiviral treatment is not delayed. ~Clay Smith

Sources

• Covid-19: What is the evidence for the antiviral Paxlovid? BMJ 2022;377:o1037. doi:10.1136/bmj.o1037
• Three more points about Paxlovid for covid-19. BMJ 2022; 377
• Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for Paxlovid [online], 2022.