The antivirals nirmatrelvir with ritonavir (Paxlovid), molnupiravir (Lagevrio) and remdesivir (Veklury) are available for:
Convalescent plasma (CCP) containing anti-SARS-CoV-2 antibodies is authorized for treatment of COVID-19 in immunosuppressed patients (hospitalized or non-hospitalized), however efficacy data in this population remains limited.
Outpatient therapeutics are not a substitute for vaccination in people for whom vaccination is recommended. Recommend COVID-19 vaccination as the best strategy to prevent severe COVID-19 illness, hospitalization and death.
Antivirals work by targeting specific proteins on the SARS-CoV-2 virus to prevent virus replication within the host cell.
Two different types of antivirals are available:
In clinical trials, antivirals as an outpatient therapy reduce the risk of hospitalization and death by 88% with Paxlovid, 87% remdesivir and 30% with molnupiravir. Antivirals have also significantly reduced the risks of hospitalization and death among high-risk non-hospitalized patients during periods of Omicron circulation, including among highly vaccinated populations.
Antivirals are not authorized for pre-exposure or post-exposure prophylaxis to prevent COVID-19.
Antivirals are available for people who have tested positive for SARS-CoV-2, regardless of their vaccination status.
Oral antivirals are available for people who meet all of the following conditions:
Intravenous Veklury (remdesivir) is approved for people who meet all of the following conditions:
Providers can use HHS's COVID-19 Decision Support Tool (PDF, December 2022) to support their clinical decisions.
Oral antiviral treatment must be administered within five days of symptom onset, but it is most effective the sooner patients begin. Treatment should be offered to any eligible patient at higher risk for severe COVID-19, regardless of vaccination status (Shaw, 2022).
Paxlovid is the preferred treatment for eligible patients ages 12 years and older.
Paxlovid can alter the concentrations of other drugs, so it is important to assess for potential drug-drug interactions. Approved label includes a boxed warning with instructions for prescribers. Several resources are available on steps that can be taken to avoid significant interactions with commonly prescribed medications, such as brief suspension or dose reduction of other medications. Do not prescribe Paxlovid for patients who are taking rivaroxaban or salmeterol; avoid it in patients with severe renal impairment (eGFR <30).
Paxlovid is not recommended for patients with severe kidney (eGFR <30 mL/min) or liver (Child-Pugh Class C) impairment.
Special renal dose packs (Paxlovid 150 mg; 100 mg) are available for patients with moderate renal impairment (eGFR ≥30 to <60 mL/min).
Patients on ritonavir- or cobicistat-containing HIV or HCV regimens should continue their treatment as indicated.
The following resources are available to assess and manage potential drug-drug interactions:
The following strategies can facilitate the use of Paxlovid in special populations:
Lagevrio should be prescribed for patients ages 18 years and older for whom alternative FDA-authorized COVID-19 treatment options are not accessible or clinically appropriate.
Lagevrio is not recommended during pregnancy. Prescribing providers should advise individuals of childbearing potential to use effective contraception correctly and consistently for the duration of treatment and for four days after the last dose of Lagevrio.
Breastfeeding is not recommended during treatment and for four days after the last dose of Lagevrio. A lactating individual may consider interrupting breastfeeding and pumping and discarding breast milk during this time.
Men of reproductive potential who are sexually active with women of childbearing potential should use a reliable method of contraception correctly and consistently during treatment and for at least three months after the last dose.
Veklury (remdesivir) is available for adults and children 28 days and older. It is administered daily for 3 consecutive days via intravenous infusion and treatment should start within 7 days of symptoms onset.
Therapy is contraindicated for patients with a history of clinically significant hypersensitivity reactions to its active ingredients or any other components of the product.
Veklury is not recommended for patients with severe kidney disease (eGFR <30 mL/min), though data suggest it can be used in patients with an eGFR of <30 mL/min if the potential benefits outweigh the risks. (NIH Treatment Guidelines)
Prior to initiating treatment with Veklury, the FDA recommends performing renal function (eGFR), liver function, and prothrombin time tests as clinically appropriate and repeating these tests during treatment as clinically indicated.
For more information, see the Veklury Label Sheet (PDF)
COVID-19 rebound is the term used describe a recurrence of symptoms or SARS CoV-2 antigen positivity, which can occur between 2 and 8 days after initial recovery. Recent studies suggest that patients who experience rebound have an extremely low probability of developing severe COVID-19. Retreatment is not currently recommended. The potential for COVID-19 rebound after antiviral treatment is not a reason to avoid prescribing.
People with rebound can transmit to others, and patients should re-isolate for at least 5 days from the recurrence of symptoms per CDC guidance. It is important to advise your patients that COVID-19 rebound does not represent a failure of treatment or resistance.
Prescribing Oral Antiviral Therapy
Paxlovid and Lagevrio (molnupiravir) are available in pharmacies throughout NYC. Visit the COVID-19 Therapeutics Locator or the Test to Treat Locator to find the nearest location. See below for instructions on how to send a prescription to Alto Pharmacy for free home delivery to patients.
Oral antivirals can only be prescribed by a physician, advanced practice registered nurse or physician assistant. Paxlovid can also be prescribed by pPharmacists with certain limitations. For more information on prescribing Paxlovid, see the Paxlovid Checklist Tool for Prescribers (PDF).
Prescriptions placed with Alto Pharmacy will be delivered the same or next day to the patient’s preferred address at no cost.
Complete the following steps to prescribe an oral antiviral medication for a patient:
Ordering Intravenous Antiviral Therapy (Remdesivir)
Veklury can be given in skilled nursing facilities, home health care settings and outpatient facilities such as infusion centers as long as severe hypersensitivity reactions, such as anaphylaxis, can be managed.
Veklury (remdesivir) is commercially available through Gilead Pharmaceuticals and multiple distributors such as AmerisourceBergen, Cardinal, or McKesson. To order, non-hospitals can contact AmerisourceBergen Specialty Distribution by calling 1-800-746-6273 or emailing remdesivir@AmerisourceBergen.com. Visit vekluryhcp.com for coding and reimbursement information and gileadadvancingaccess.com for patient assistance resources.
Facilities and providers that see large numbers of immunosuppressed patients (such as transplant and oncology centers), high-risk pediatric populations, or other patients for whom Paxlovid may not be clinically appropriate are encouraged to offer Veklury in the outpatient setting. This can be done in collaboration with tertiary care centers.
Patients can also visit ExpressCare or call 212-COVID19 (212-268-4319) or 311 for a treatment evaluation and to schedule an appointment for remdesivir infusions if indicated through NYC Health + Hospitals.
Patient Education on Antivirals
People at increased risk of severe COVID-19 and their caregivers should be advised:
Patients who do not have a health provider or are uninsured can visit ExpressCare or call 212-COVID19 (212-268-4319) or 311 to speak with a doctor about treatment options or find a Test to Treat site at nyc.gov/covidtest or aspr.hhs.gov/TestToTreat.
Patient Handout: COVID-19 Treatments Are Available (PDF)
Due to the high prevalence of resistant subvariants, monoclonal antibody products bebtelovimab and Euvsheld are no longer authorized in the US. Providers that have product on hand should continue to report inventory for Evusheld in HPOP once per week.
See NYS Department of Health Advisory: Updates on COVID-19 Treatment Recommendations for more information.
Facilities that have offered monoclonal antibodies are strongly encouraged to offer outpatient remdesivir infusions as part of their treatment programs for patients unable to take Paxlovid; particularly for those at highest risk for severe outcomes from COVID-19 (65 years and older, immunocompromised, 50-64 years of age and unvaccinated).
Providers should advise patients who have received Evusheld that breakthrough infections are possible. Patients with moderate to severe immune compromise should be advised to remain up to date on COVID-19 vaccinations, counseled on general prevention measures to avoid SARS-CoV-2 exposure, and have at home COVID-19 tests available with a plan in place to seek timely medical care and treatment if they develop symptoms.