Paxlovid (nirmatrelvir co-packaged with ritonavir)

• Yes. The EUA for Paxlovid is still active and authorizes the use of Paxlovid 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) who are at high risk for progression to severe COVID-19, including hospitalization or death.
• Paxlovid is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19.
• Paxlovid is not authorized for use as pre-exposure or post-exposure prophylaxis for prevention of COVID-19.

Yes, health care providers and patients must be aware of the following warnings and precautions:

• The concomitant use of Paxlovid and certain other drugs may result in potentially significant drug interactions.
• Hypersensitivity reactions: Anaphylaxis and other hypersensitivity reactions have been reported with Paxlovid. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue Paxlovid and initiate appropriate medications and/or supportive care.
• Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir.
• HIV-1 drug resistance: Paxlovid use may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.

Please refer to the Paxlovid fact sheet for health care providers for additional information on warnings and precautions.

As of November 1, 2023, Paxlovid became available for purchase through the commercial market. In addition, orders of USG-procured Paxlovid may be submitted through December 15, 2023. These orders are made against approved out of cycle requests. Out of cycle requests require up to 48 hours to process. To allow sufficient time for ordering, out of cycle requests should be sent 48 hours in advance. After December 15, federal entities can continue to order from the USG supply through the Health Partner Ordering Portal.

Through December 31, 2024, individuals covered under federal programs, such as Medicare or Medicaid, and uninsured patients are eligible for the USG Patient Assistance Program (PAP) operated by Pfizer and can receive Paxlovid at no cost. Health care providers and dispensing locations can provide information to patients regarding eligibility and how eligible patients can enroll in the PAP to obtain free product. In addition, there is a Co-Pay Savings Program for eligible commercially insured patients. Additional information for patients and health care providers is available.

Rebound, which is defined as experiencing recurrence of symptoms and/or SARS CoV-2 antigen positivity after initial resolution, has been observed not only among patients treated with Paxlovid but also occurs in patients receiving no treatment and in patients treated with other COVID-19 therapeutics.

Recent studies suggest patients experiencing rebound have an extremely low probability of developing severe COVID-19. Further studies on this phenomenon are ongoing.

Additional guidance on the management of patients experiencing rebound is available.

• NIH Therapeutic Management of Nonhospitalized Adults With COVID-19
• FDA Fact Sheet for Health Care Providers for Paxlovid (nirmatrelvir and ritonavir)
• FDA Frequently Asked Questions for Paxlovid
• Side-by-Side Outpatient Therapeutics Overview
• Therapeutics Clinical Implementation Guide
• COVID-19 Therapeutics Decision Aid
• Conditions associated with higher risk for severe COVID-19
• Email any questions to COVID19therapeutics@hhs.gov.

Paxlovid is for adults (ages 18 years of age and older) and children (12 years of age and older weighing at least 40 kg) for treatment of mild to moderate COVID‑19 and who are at high risk for progression to severe COVID‑19 disease, including hospitalization and death. Criteria include:

• Have mild to moderate COVID-19 and are within 5 days of symptom onset
• Have one or more risk factorsfor severe COVID-19

The U.S. Food and Drug Administration’s (FDA) Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers is a useful tool for assessing eligibility.

See FDA’s Fact Sheet for Healthcare Providers for detailed information about Paxlovid.

Per the current CDC’s Interim Clinical Considerations for COVID-19 Treatment in Outpatients guidelines, risk factors include:

• Age 50 years or older, with risk increasing substantially at age ≥ 65 years
• Being unvaccinated or not being up to date on COVID-19 vaccinations
• Specific medical conditions and behaviors

For additional information, please see the National Institutes of Health’s COVID-19 Treatment Guidelines: Clinical Spectrum of SARS-CoV-2 Infection.

Health care providers should also proactively counsel high-risk patients about the availability of effective therapeutics and discuss a COVID-19 Action Plan with their patients.

The benefit of a 5-day treatment course of Paxlovid was demonstrated in the clinical trial that supported the EUA. This study that among non-hospitalized, unvaccinated patients at high risk of progression to severe disease, treatment with Paxlovid reduced the risk of hospitalization or death by 88%.¹

Observational data, including vaccinated patients, from Israel,² Hong Kong,³ and the United States is consistent with benefit in high-risk patients:

• 46% reduction in hospitalizations and deaths compared to the untreated²
• 65% reduction in death compared to non-users³
• 51% lower hospitalization rate within 30 days after diagnosis than those who were not prescribed Paxlovid⁴

References:

1. Jennifer Hammond, et al. New Engl J Medicine. 2022;386(15):NEJMoa2118542. doi: 10.1056/nejmoa2118542
2. Ronza Najjar-Debbiny, et al. Clinical Infectious Diseases, 2022; ciac443, https://doi.org/10.1093/cid/ciac443
3. Carlos K.H. Wong, et al. Lancet Infectious Disease, 2022; doi: https://doi.org/10.1016/ S1473-3099(22)00507-2
4. Melisa M. Shah, et al. MMWR. https://www.cdc.gov/mmwr/volumes/71/wr/mm7148e2.htm?s_cid=mm7148e2_w

Drug-drug interactions are important when considering whether to prescribe Paxlovid. Paxlovid may impact the concentration of concomitantly administered medications.

Despite its potential for drug-drug interactions, many commonly-used medications can be safely co-administered with Paxlovid. The prescriber should perform a thorough medication reconciliation, including over-the-counter medications and supplements, prior to prescribing Paxlovid.

FDA’s Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers includes a helpful table with medications that interact with Paxlovid, and the recommended action for the prescriber.

• Veklury (remdesivir) is a preferred antiviral medication for mild to moderate COVID-19. Veklury is given intravenously, once daily for 3 consecutive days.
• Lagevrio (molnupiravir) (oral antiviral) is an alternative medication when preferred therapies authorized or approved by FDA are not clinically appropriate or available.