FDA authorized Paxlovid (nirmatrelvir and ritonavir) in December 2021 for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing who are also at high risk for progression to severe COVID-19, including hospitalization or death.
Paxlovid is now widely available in community pharmacies. Although the number of COVID-19 hospitalizations has decreased dramatically since early 2022, some high-risk patients are still getting sick enough to require hospital admission, and early treatment with Paxlovid and other available authorized or approved therapeutics could make a difference.
In this CDER Conversation, Dr. John Farley, director of the Office of Infectious Diseases, provides useful information that can help health care providers in decision making regarding Paxlovid, the preferred therapy for the management of non-hospitalized adults with COVID-19, according to the National Institutes of Health COVID Treatment Guidelines.
Table of Contents
What does “direct SARS-CoV-2 viral testing” mean? Do patients need a positive polymerase chain reaction (PCR) test to be treated with Paxlovid?
Direct SARS-CoV-2 viral tests are used to diagnose infection by SARS-CoV-2, the virus that causes COVID-19. Direct SARS-CoV-2 viral tests include two types of diagnostic tests for COVID-19:
- Molecular tests, such as PCR tests, that detect the virus’s genetic material.
- Rapid antigen diagnostic tests that detect specific proteins from the virus.
There are many rapid antigen tests authorized for home use. Patients in the authorized population who report a positive home test result from a rapid antigen diagnostic test to their provider are eligible for Paxlovid under the emergency use authorization (EUA). A positive result on a PCR test also meets the requirement under the EUA to have a positive test result. Confirmation of a positive home rapid antigen diagnostic test with additional direct SARS-CoV-2 viral testing, such as a PCR, is not required. Serologic tests are not considered to be direct SARS-CoV-2 viral tests.
How should health care providers assess a patient for “high risk for progression to severe COVID-19”?
Patients in the authorized population with a risk factor for progression to severe COVID-19 are eligible for Paxlovid under the EUA even if they are fully vaccinated. Patients do not have to have more than one risk factor to be considered “high risk”.
We recognize that risk factors have changed over time, and that it is appropriate to consider vaccination status in assessing a patient’s risk for progression to severe COVID-19.
For more information on medical conditions and factors associated with increased risk for progression to severe COVID-19, please visit the Centers for Disease Control and Prevention (CDC) website.
Are there tools to help health care providers manage potential drug-drug interactions?
Yes. FDA recently updated the Fact Sheet for Health Care Providers for Paxlovid to provide more specific recommendations for some drugs. We also developed a Prescriber Patient Eligibility Screening Checklist. The checklist is intended to support clinical decision making, and I believe it will be a helpful addition to any prescriber’s “toolbox.”
Paxlovid contains nirmatrelvir and ritonavir. Ritonavir is a strong inhibitor of cytochrome P450 3A. Potential drug-drug interactions are an important consideration. However, several commonly used medications with potential interactions such as statins, oral contraceptives, and HIV medications can be easily managed under provider supervision. Recommendations are provided in the Health Care Provider Fact Sheet and the Eligibility Screening Checklist Tool along with an alphabetized list of other drugs with potentially significant drug interactions.
Other resources regarding management of drugs with potentially significant drug interactions with Paxlovid include:
Is dose adjustment of Paxlovid needed for patients with moderate renal impairment?
Yes. Paxlovid is now supplied in two different dose packs, one for standard dosing and one for moderate renal impairment dosing.
- In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of Paxlovid is 150 mg nirmatrelvir (one 150 mg tablet) and 100 mg ritonavir (one 100 mg tablet) twice daily for five days.
- Patients with mild renal impairment (eGFR ≥60 to <90 mL/min) should receive the standard dose of 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together orally twice daily for five days.
- Paxlovid is not recommended at this time in patients with severe renal impairment (eGFR <30 mL/min).
Health care providers may rely on patient history and access to the patient’s health records to make an assessment regarding the likelihood of renal impairment. Providers may consider ordering a serum creatinine or calculating the estimated glomerular filtration rate (eGFR) for certain patients after assessment on a case-by-case basis.
How can I locate a community pharmacy that has Paxlovid in stock?
Paxlovid is now widely available at community pharmacies. The U.S. government maintains a locator tool for COVID-19 therapeutics that lists community pharmacies that have Paxlovid in stock. Use the search glass icon to enter the patient’s zip code. Pharmacies will be listed by proximity.
What do we know about the case reports of patients developing symptoms again after completing a course of Paxlovid?
FDA is aware of the reports of some patients developing recurrent COVID-19 symptoms after completing a treatment course of Paxlovid. In some of these cases, patients tested negative on a direct SARS-CoV-2 viral test and then tested positive again.
The benefit of a 5-day treatment course of Paxlovid was demonstrated in the clinical trial that supported the EUA. This study showed that among non-hospitalized patients at high risk of progression to severe disease, treatment with Paxlovid reduced the risk of hospitalization or death by 88%. Reductions in hospitalization and death were also demonstrated in clinical trials of other available approved (Veklury [remdesivir]) or authorized (Lagevrio [molnupiravir]) antiviral agents.
In light of these reports, additional analyses of the Paxlovid clinical trial data have been performed. In the Paxlovid clinical trial, some patients (range 1-2%) had one or more positive SARS-CoV-2 PCR tests after testing negative, or an increase in the amount of SARS-CoV-2 detected by PCR, after completing their treatment course. This finding was observed in patients treated with the drug as well as patients who received placebo, so it is unclear at this point that this is related to drug treatment. Additional analyses show that most of the patients did not have symptoms at the time of a positive PCR test after testing negative, and, most importantly, there was no increased occurrence of hospitalization or death or development of drug resistance.
These reports, then, do not change the conclusions from the Paxlovid clinical trial which demonstrated a marked reduction in hospitalization and death.
We are continuing to review data from clinical trials and will provide additional information as it becomes available. However, there is no evidence of benefit at this time for a longer course of treatment (e.g., 10 days rather than the 5 days recommended in the Provider Fact Sheet for Paxlovid) or repeating a treatment course of Paxlovid in patients with recurrent COVID-19 symptoms following completion of a treatment course.
In summary, Paxlovid reduces the risk of hospitalization and death for patients with mild-to-moderate COVID-19 at high risk of disease progression. Health care providers should consider treatment with Paxlovid or other approved or authorized therapeutics in accordance with the approved labeling or authorized Health Care Provider Fact Sheets. Patients who test positive for SARS-CoV-2 who have symptoms should discuss treatment options with their health care provider as soon as possible after testing positive. Health care providers and patients should refer to CDC recommendations regarding patient isolation, and should wear a mask and isolate if they have any symptoms regardless of whether or not they have been treated with an antiviral agent.
Thank you, Dr. Farley. Do you have any final remarks you’d like to share with health care providers about Paxlovid?
I would like to reiterate that Paxlovid is now widely available at community pharmacies. There is strong scientific evidence that it reduces the risk of hospitalization and death in patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. It is also expected to be effective against the Omicron variant. For more information about the EUA for Paxlovid, including possible risks of use, the Fact Sheet for Health Care Providers, and Prescriber Patient Eligibility Checklist, please visit FDA’s Emergency Use Authorizations webpage.