Who should receive outpatient therapy for COVID-19?
- 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 EUA and NIH recommendations.
- A lack of recent renal or liver function tests. The FDA EUA does not require assessment of laboratory results.
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 | FDA EUA | Oral twice daily for 5 days | ≤5 days | Age ≥12 who weigh ≥40kg | Providers Patient/caregivers FAQs |
2. Remdesivir | FDA Approved | IV infusion daily for 3 days | ≤7 days | Adults and children age ≥28 days who weigh ≥3kg | Providers Patients FAQs |
3. Molnupiravir | FDA EUA | Oral twice daily for 5 days | ≤5 days | Adults ≥18 (not recommended in pregnancy) | Providers Patient/caregivers FAQs |
Paxlovid
Paxlovid (nirmatrelvir 300 mg with ritonavir 100 mg), 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.
Studies have shown that Paxlovid:
- Reduces the risk for hospitalization and death by 50-88% among unvaccinated people and by 45–50% among vaccinated or previously infected people.1,2,3 Recent studies in highly COVID-19 immune populations conducted during omicron circulation show significant reductions in hospitalizations among patients aged 18 and older with risk factors for severe disease (see Table below).
- May decrease the risk of developing post-COVID symptoms. 4,5,6,7 The extent and scale of impact that long COVID may have on individual and population health are yet to be revealed and may be quite significant.
- Decreases SARS-CoV-2 viral load faster compared with people not treated, suggesting the potential for decreased transmission and isolation time for test-result-based isolation protocols.1
- Has been shown to be safe, including in older adults.1,8 Risks are minimal, especially when weighed against benefits.
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.
The potential for COVID-19 rebound is not a reason to avoid prescribing Paxlovid
- COVID-19 rebound is the term used to describe a recurrence of symptoms and/or SARS CoV-2 antigen positivity which can occur between 2 and 8 days after initial recovery. The etiology of this phenomenon is not known. Recent small studies suggest that rebound may happen when people have a strong immune response to COVID-19; neither the development of resistance nor the absence of neutralizing antibody were likely causes of rebound 9, 10
- Rebound has been observed in the minority of patients treated with Paxlovid or molnupiravir11,12 It also occurs in patients who did not receive COVID-19 therapeutics 13,14 A preprint by Deo et al found that 1 out of 8 people who did not receive COVID-19 therapy experienced rebound. Those that rebounded were more likely to be older. Among those that rebounded, only 10% had symptoms.
- Rebound is typically mild. Recent studies suggest that patients who experience rebound have an extremely low probability of developing severe COVID-19. Retreatment is not currently recommended.
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
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.
Molnupiravir sample prescription:
FDA: Letter of authorization | FAQs on the EUA | Fact sheet for health providers | Fact sheet for patient/caregivers
Summary of Effectiveness
Table: Summary of studies analyzing the effectiveness of oral antivirals during omicron | ||||
---|---|---|---|---|
Study | Population | Drug | Time analyzed | Outcomes |
Ganatra et al., 2022 |
|
Paxlovid | December – April 2022 |
|
Najjar-Debbiny et al. 2022 |
|
Paxlovid | January - February 2022 |
|
Najjar-Debbiny et al, 2022 |
|
Molnupiravir | January-February 2022 |
|
Arbel et al., 2022 |
|
Paxlovid | January - March 2022 |
|
Dryden-Peterson et al., 2022 |
|
Paxlovid | January - July 2022 |
|
Wong et al. 2022 |
|
Paxlovid and molnupiravir | February -April 2022 |
|
Wong et al., 2022 |
|
Paxlovid and molnupiravir | February – June 2022 |
|
Radcliffe et al. 2022 |
|
Molnupiravir | January – February 2022 |
|
Butler et al. 2022 |
|
Molnupiravir | December 2021-April 2022 |
|
Pre-exposure prophylaxis
On January 1-26-23 the FDA revised the Emergency Use Authorization for Evusheld (tixagevimab/cilgavimab) to limit its use to when the combined frequency of non-susceptible SARS-CoV-2 variants nationally is less than or equal to 90%. Based on this revision, Evusheld is not currently authorized for use in the U.S. until further notice by the Agency. See FDA announcement.
Evusheld is a combination of two long-acting anti-SARS-CoV-2 monoclonal antibodies administered via intramuscular injection that was used for pre-exposure prophylaxis to protect against SARS-CoV-2 infection. It lost FDA authorization for use in January 2023 due the high prevalence of variants resistant to Evusheld.
With the loss of the only pre-exposure prophylaxis medication to prevent COVID-19, it is important that that persons who are moderately to severely immunocompromised, those who might have an inadequate immune response to COVID-19 vaccination, and those with contraindications to receipt of COVID-19 vaccines, be counseled to exercise caution and recognize the need for additional preventive measures. In addition, they should be advised to have a personal COVID-19 care plan that includes prompt testing at the onset of COVID-19 symptoms and rapid access to antivirals if SARS-CoV-2 infection is detected. See CDC MMWR Information for Persons Who Are Immunocompromised Regarding Prevention and Treatment of SARS-CoV-2 Infection in the Context of Currently Circulating Omicron Sublineages — United States, January 2023
Information for providers with Evusheld product. The U.S. Government recommends that facilities and providers with Evusheld retain all product in the event that SARS-CoV-2 variants which are neutralized by Evusheld become more prevalent in the U.S. in the future. Retained product must be appropriately held in accordance with storage conditions detailed in the authorized Fact Sheet for Health Care Providers (PDF) and the Letter of Authorization (PDF). Also see: Expiration Dating Extension - COVID-19 Therapeutics
Post-exposure prophylaxis
- At this time there are no therapeutics authorized for post-exposure prophylaxis that are active against Omicron
Procuring medication for your patients
- If you are interested in becoming a therapeutics provider, please contact DPH-Therapeutics@ph.lacounty.gov.
- This information is intended for medical providers. Information for the public is available here.
- Patients who are unable to access oral COVID-19 therapeutics through their own provider or who do not have health insurance can be referred to a Test to Treat program or the DPH Public Health Call Center/Tele-Health service, which provides testing, consultation, and prescriptions. 1-833-540-0473 - open 7 days a week, 8:00 am-8:30 pm.
To search by zip code for locations that offer Test-to-Treat (testing, medical visits, and medication), use the federal Get medication for COVID-19 locator.
Patients who are unable to access oral COVID-19 therapeutics through their own provider or who do not have health insurance can be referred to a Test to Treat program or the DPH Public Health Call Center/Tele-Health service which provides testing, consultation, and prescriptions. 1-833-540-0473 - open 7 days a week 8:00 am-8:30 pm.
To search by zip code for locations that fill prescriptions use the federal Get medication for COVID-19 locator.
Patients who are unable to access oral COVID-19 therapeutics through their own provider or who do not have health insurance can be referred to a Test to Treat program or the DPH Public Health Call Center/Tele-Health service which provides testing, consultation, and prescriptions. 1-833-540-0473 - open 7 days a week 8:00 am-8:30 pm.
Facilities can order directly from manufacturer: vekluryhcp.com
Reimbursement and Billing
California’s Department of Health Care Services (DHCS) will still accept claims for individuals enrolled in the COVID-19 Uninsured Group Program. Individuals must apply for the COVID-19 Uninsured Group Program through a Medi-Cal Qualified Provider (QP). QPs are providers of the following programs: Presumptive Eligibility for Pregnant Women, Breast and Cervical Cancer Treatment Program, Hospital Presumptive Eligibility, and Child Health and Disability Prevention. Providers must submit applications via the COVID-19 Uninsured Group Application Portal. Providers can submit their COVID-19 testing, testing-related, and treatment claims to DHCS for claims processing.
Cost Sharing
COVID-19 Therapeutics: Fees for Oral Antivirals
- Provider Assessment
- Bill insurance if/when available
- For uninsured and underinsured, encourage use of free, low-cost care (e.g., HRSA, State-run clinics)
- May share cost (full fee or co-pay) with patients
- Testing
- Encourage use of ICATT sites that provide free testing
- Most Walgreens and CVS T2T sites are enrolled in ICATT (working towards all sites)
- Otherwise non-ICATT sites may charge patients
- Patients are able to use (free) at-home test
- Encourage use of ICATT sites that provide free testing
- Medication
- Free for all. No cost sharing with patients
- Dispensing Fee
- No cost sharing with patients
COVID-19 Therapeutics: Fees for monoclonal antibodies
- Provider Assessment
- Bill insurance if/when available
- For uninsured and underinsured, encourage use of free, low-cost care (e.g., HRSA, State-run clinics)
- May share cost (full fee or co-pay) with patients
- Medication
- Free for all. No cost sharing allowable
- Administration Fee
- Bill insurance if/when available
- For uninsured and underinsured, encourage use of free, low-cost care (e.g. HRSA, State-run clinics)
- May share cost (full fee or co-pay) with patients
Resources
- HRSA COVID-19 Uninsured Fund Updates
- CMS reimbursement information for mAbs
- CMS reimbursement information for oral antivirals
- CMS Guidance for Medicare
- DHCS Billing guidance for pharmacy providers on oral antivirals
- CMS HCPCS code for remdesivir reimbursement when administered in an outpatient setting