COVID-19 Outpatient Treatment

Who should receive outpatient therapy for COVID-19?

Clinicians should prescribe COVID-19 treatment to the extent possible to outpatients who meet all of the following:

Have mild or moderate COVID-19
Are within 5 days of symptoms onset for Paxlovid and molnupirivir or 7 days of symptom onset for IV remdesivir
Have one or more risk factors for severe COVID-19 including:
- Age over 50 years, especially those 65 and older, regardless of the presence of a medical condition
- Being unvaccinated or not being up to date on COVID-19 vaccinations
- Being in a racial or ethnic minority group
- Having common underlying health conditions and behaviors such as physical inactivity, obesity, depression, smoking (former or present), and disabilities. See CDC comprehensive discussion.

For more information, see the CDC webpage Interim Clinical Considerations for COVID-19 Treatment in Outpatients.

To view the IDSA COVID-19 Risk Continuum graphic see Understanding Risk for Severe COVID-19 webpage.

The following factors should NOT be reasons to withhold COVID-19 treatment:

Being fully or partially vaccinated
Having a history of prior SARS-CoV-2 infection
Presence of only mild disease. Patients with mild symptoms are included in criteria for outpatient treatment according to the FDA approved label, authorized Fact Sheet for Healthcare Providers for the EUA, and NIH recommendations.
A lack of recent renal or liver function tests. The FDA does not require assessment of laboratory results.

Clinicians should have a low threshold to prescribe COVID-19 therapeutics given the broad range of individuals who are at higher risk for severe COVID-19 and can benefit from COVID-19 treatment.

Treatment should be started as soon as possible after the onset of symptoms, ideally within the first 24 hours.

Outpatient Treatments for COVID-19

Three antiviral therapies are currently FDA approved or authorized for outpatient treatment of COVID-19 infection and recommended by the NIH COVID-19 Treatment Guidelines Panel. They are not approved for pre- or post-exposure prophylaxis. Importantly, they retain full activity against the current variant mix in California.

Note: The FDA has removed the requirement for a positive SARS-CoV-2 viral test in order to prescribe these medications. Although the agency still strongly recommends the use of viral testing to help diagnose COVID-19 this change allows for providers to consider treatment in the rare instances where an individual with a known exposure who develops signs and symptoms consistent with COVID-19 presents with a negative test. See FDA product specific FAQs for more information.

Antiviral Medication (in order of preference)	FDA Status	Mode/duration of Administration	Start time from symptom onset	Age/Weight	Fact sheets/FAQs
1. Paxlovid	Approved (adults) EUA (age 12-17)	Oral twice daily for 5 days	≤5 days	Age ≥12 who weigh ≥40kg	Providers Approved label EUA fact sheet Patient/caregivers FAQs
2. Remdesivir	Approved	IV infusion daily for 3 days	≤7 days	Adults and children age ≥28 days who weigh ≥3kg	Providers Patients FAQs
3. Molnupiravir	EUA	Oral twice daily for 5 days	≤5 days	Adults ≥18 (not recommended in pregnancy)	Providers Patient/caregivers FAQs

See HHS Side-by-Side Overview of Therapeutics for additional information.

IDSA outpatient treatment guideline for information on when to use each product Web | PDF COVID-19 Therapeutics FAQs. FAQs for clinics, providers, and pharmacists who are prescribing COVID-19 treatment.

COVID-19 Therapeutics FAQs for clinics, providers, and pharmacists from the Center for Care Innovations, Physicians for a Health California, and CDPH Therapeutics Task Force.

Paxlovid

Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use), given within 5 days of symptom onset, is the preferred treatment for adults and pediatric patients (12 years of age and older weighing at least 40 kg) with symptomatic COVID-19 and risk factors for progression. It is taken orally twice a day for 5 days.

See the FDA Paxlovid approved label/fact sheet (EUA) for detailed prescribing information including.

Most commonly used medications can be safely co-administered with Paxlovid

Paxlovid can alter the concentrations of other drugs, so it is important to assess for potential drug-drug interactions.
Many commonly used medications can be safely co-administered with Paxlovid despite its drug-drug interaction potential. See NIH guidance Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications and the Liverpool COVID-19 Drug Interactions website
The Infectious Disease Society of America offers guidance on simple steps that can be taken to avoid significant interactions with commonly prescribed medications, such as brief suspension or dose reduction.

FDA Paxlovid patient eligibility checklist PDF

Paxlovid package information

Standard packaging for patients with normal renal function:
- 300 mg nirmatrelvir;100 mg ritonavir - Each carton contains 30 tablets divided in 5 daily-dose blister cards.
- Each blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
New packaging option for patients with reduced renal function: See Dear Healthcare Provider Letter
- 150 mg nirmatrelvir; 100 mg ritonavir - Each carton contains 20 tablets divided in 5 daily-dose blister cards.
- Each blister card contains 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.

Paxlovid sample prescriptions

Prescription for patients with normal renal function

Prescription for patients with reduced renal function

HHS Paxlovid website includes prescribing information, FAQs, and other resources for providers and patients.

FDA: Letter of authorization | FAQs on the EUA | FDA letter: new medication packaging for patients with moderate renal impairment | Fact sheet for health providers | Fact sheet for patient/caregivers

Other resources: Pharmacist Authority to Prescribe

Remdesivir

Remdesivir (Veklury) is the only treatment approved for children under 12 years of age. It is given as an IV infusion for a total of 3 days initiated as soon as possible and within 7 days of symptom onset.

In clinical trials, remdesivir reduced the risk of hospitalization or death by 87% among high-risk unvaccinated patients with COVID-19 treated within 7 days of symptom onset (Gottlieb, 2021).

Given the emergence of variants resistant to mAbs, providing remdesivir in the outpatient setting may be of particular importance for facilities and providers that see large numbers of immunosuppressed patients such as transplant and oncology centers, or high-risk pediatric populations. Providers are encouraged to order remdesivir to have on hand for patients unable to take Paxlovid.

FDA approved for the treatment of COVID-19 in adults and pediatric patients (28 days of age and older weighing at least 3 kilograms) who are:
- Hospitalized, or
- Not hospitalized and have mild-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization and death.
  Note: In December 2022, the FDA revised the remdesivir labeling to remove having a positive SARS-CoV-2 viral test result from the indication.
For information regarding purchasing or how to access remdesivir, please email remdesivir@amerisourcebergen.com, or call 1-800-746-6273 or reach out directly to your AmerisourceBergen representative.
HHS is asking providers who administer outpatient Veklury (remdesivir) to add their infusion site to the COVID-19 Therapeutics Locator in order to improve public awareness and product access. Only information provided by the infusion site will be visible on the locator. Infusion sites can opt out of being on the locator at any time. Infusion sites can learn more and opt into the therapeutics locator here.
CMS has created the Healthcare Common Procedure Coding System (HCPCS) code J0248 for reimbursement when administered in an outpatient setting. This code is available for use by all payers and is effective for dates of service on or after December 23, 2021. Additional information is available here.

FDA: Prescribing information | Press release FDA approval for children
Information for providers vekluryhcp.com |
Information for patients wwwwww.veklury.com

Molnupiravir

Molnupiravir (Lagevrio) is authorized as an alternative therapy when Paxlovid and remdesivir are not available, feasible to use, or clinically appropriate. It is given as 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days. Treatment started as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.

Molnupiravir is a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis.
Due to concern for side effects and decreased risk reduction compared to other available medications, molnupiravir should only be used if other treatments are not available or not clinically appropriate.
Guidance is now available on the provider fact sheet for the preparation and administration of molnupiravir via nasogastric and orogastric tube.
Several studies have shown a risk reduction in severe disease after molnupiravir treatment with the most significant benefit in those at highest risk or elderly (≥75 years of age). In addition, there is evidence of more rapid symptom resolution and viral load reductions in people treated with molnupiravir. See table below.
Use in adults 18 and older only. Not recommended in pregnancy. If the provider and patient choose to use the product during pregnancy, it is advised that the patient be registered in the Merck Pregnancy Surveillance Program.
Females of childbearing potential should use a reliable method of contraception correctly and consistently, as applicable, for the duration of treatment and for 4 days after the last dose of molnupiravir.
Males of reproductive potential who are sexually active with females of childbearing potential should use a reliable method of contraception correctly and consistently during treatment and for at least 3 months after the last dose.
Providers should carefully review the Fact sheet for health providers before prescribing to ensure that the patient’s condition warrants treatment, that there are no drug interactions, and that there are contraindications to therapy.