The U.S. Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) PDF on December 22, 2021 for nirmatrelvir co-packaged with ritonavir (Paxlovid) to be used for the treatment of mild-to-moderate COVID-19 in patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
Paxlovid is comprised of nirmatrelvir, a SARS-CoV-2 protease inhibitor, co-packaged with ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor. Ritonavir, which has no activity against SARS-CoV-2 on its own, is included to inhibit the CYP3A-mediated metabolism of nirmatrelvir and consequently increase nirmatrelvir plasma concentrations to levels anticipated to inhibit SARS-CoV-2 replication.
Clinical Trial Data
Final results from all high-risk patients enrolled in Pfizer's Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) study (n= 2,246) confirmed prior results of interim analysis showing Paxlovid reduced risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) compared to placebo; no deaths compared to placebo in non-hospitalized, high-risk adults with COVID-19.
Paxlovid and SARS-CoV-2 Variants
Paxlovid is expected to be effective against all variants currently circulating in California, including Omicron.
Additional Use Considerations
Paxlovid is authorized for treatment only. The Fact Sheet for Health Care Providers (PDF), which includes criteria for the full authorization of use, contraindications, and drug interactions should be reviewed prior to administration of the medication.
The following should be considered:
- Paxlovid is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19. Paxlovid is not a substitute for COVID-19 vaccination.
- Recent in vitro data confirm that nirmatrelvir is a potent inhibitor of the Omicron 3CL protease, which, combined with existing in vitro antiviral and protease inhibition data from other Variants of Concern (VoC) including Delta, suggest Paxlovid will retain activity against Omicron.
- Paxlovid may only be prescribed for individual patients by a healthcare provider (physicians, advanced practice nurses, and physician's assistants) and is not authorized for initiation of treatment in hospitalized patients, or as pre-exposure or post-exposure prophylaxis.
- Paxlovid consists of 300 mg (two 150 mg tablets) of nirmatrelvir that are co-packaged with one 100 mg tablet ritonavir, and the course is twice daily for five days. Paxlovid is not authorized for use beyond five days. To be effective, Paxlovid must be given within 5 days of symptom onset, ideally as soon as possible.
- The concomitant use of Paxlovid and certain other drugs may result in potentially significant drug interactions, and may also alter plasma concentrations of other drugs. Providers should consult the full prescribing information (PDF) prior to and during treatment for potential drug interactions. Additionally, hepatotoxicity has occurred in patients receiving ritonavir, and it is not recommended for patients with severe renal or hepatic impairment.
- Paxlovid should also be used with caution in patients with HIV, as it may lead to a risk of HIV-1 developing resistance to HIV protease-inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
Patient Prioritization During Times of Limited Supply
The National Institutes of Health (NIH) treatment guidelines on prioritization should be followed during times when supply is limited.
Allocation of Paxlovid will be to pharmacies and providers able to dispense the medication. The number of courses allocated to each county is determined using the overall COVID-19 cases in that county combined with an equity measure based on the Healthy Places Index (HPI).
Prescribing healthcare providers can locate sites where COVID-19 therapeutics are available using the HHS Therapeutics Locator. The Therapeutics Locator is based on shipments and reported utilization and is not a guarantee of availability. Providers should communicate with facilities to ensure that supply exists.
Originally published on January 19, 2022