Information about outpatient COVID-19 therapeutics for health care providers

Colorado’s supply of therapeutics is determined in part at the federal level. At this time, Colorado receives federal distributions of Paxlovid (co-packaged Nirmatrelvir and Ritonavir) (including dose packs for patients with moderate renal impairment) and Lagevrio (molnupiravir). Providers may also order the intravenous antiviral Veklury (remdesivir) directly from the manufacturer. Currently there is more than enough supply available to meet demand.

Providers who are interested in ordering Paxlovid and Lagevrio or who have questions about the COVID-19 therapeutics program should email cdphe_dcphr_covidtherapeutics@state.co.us. Once enrolled, there are utilization reporting requirements at the state and federal levels. Providers can order any time through the Health Order Partner Portal (HPOP) and CDPHE will fill the order within 24 hours. Veklury (remdesivir) must be ordered directly from the manufacturer. Find out more information about how to order Veklury (remdesivir) in general and for outpatient providers.

Providers should follow the guidelines in the NIH COVID-19 Treatment Guidelines: Therapeutic Management of Nonhospitalized Adults with COVID-19. Pediatric providers should follow the guidelines in the NIH COVID-19 Treatment Guidelines: Therapeutic Management for Nonhospitalized Children with COVID-19.

In order to meet the guidelines from HHS and help the state of Colorado fulfill our mission, reporting therapeutics use and inventory is required. Accurate reporting will allow the state to ensure equitable distribution of treatments across Colorado. Reporting is done by the facility that orders therapeutics, not the prescribing provider when a prescription is provided.

Providers that do not report regularly in HPOP risk future orders not being approved.

Reporting cadence

To meet these guidelines from HHS and help the state of Colorado fulfill our mission, twice monthly reporting is required on Paxlovid and Lagevrio by 11:59 p.m.ET on the 15th and last day of each month.

Although the following products are no longer authorized for use by the FDA or recommended for use by CDPHE, reporting of inventory is required once a month by 11:59 p.m. ET on the last day of the month for:

• Bebtelovimab (for US Government supply only).
• Sotrovimab.
• REGEN-COV and Bamlanivimab and etesevimab (Bam-Ete).
• Evusheld.

Information on FDA shelf life extensions and expirations can be found on FDA’s Expiration Dating Extension webpage. Email COVID19Therapeutics@hhs.gov with any questions. If you are having difficulty navigating HPOP, refer to the following resources:

• Get started with Oracle HPOP Provider Portal
• HPOP Therapeutics Partner Quick Start User Guide (CDC)

Refer to ASPR guidance on retention of products.

Email COVID19Therapeutics@hhs.gov with any further questions.

In general, U.S. Government (USG) distributed therapeutics are the property of USG and must be used in accordance with the Emergency Use Authorization (EUA). USG-distributed therapeutics may not be donated or otherwise used outside the United States. Check expiration dates on ASPR’s website before disposing of therapeutics.

The Department of Health and Human Services (HHS) announced the end of the federal Public Health Emergency (PHE) for COVID-19, declared under Section 319 of the Public Health Service (PHS) Act, on May 11, 2023.

The Biden-Harris Administration and state of Colorado’s continued response to COVID-19 is not fully dependent on the COVID-19 PHE, and many important initiatives, funding streams, and enforcement powers are not affected. Access to COVID-19 treatments, such as Paxlovid and Lagevrio, has generally not been affected.

Additional details and resources regarding the expiration of the PHE are provided below:

• Fact Sheet: COVID-19 Public Health Emergency Transition Roadmap
• CMS Waivers, Flexibilities, and the Transition Forward from the COVID-19 Public Health Emergency
• FDA FAQs: What happens to EUAs when a public health emergency ends?
• ASPR PREP Act Questions and Answers

Clinical educational resources on therapeutics, including training, are available for providers. Email cdphe_covid_med_guidance@state.co.us to request these resources.

The ASPR/HHS Test to Treat program allows sites to enroll as "full-service" therapeutics providers: from patient COVID-19 testing and symptom screening, to prescribing, to dispensing oral antivirals. Given that oral antivirals are only approved or authorized to be administered when started within five days of symptom onset, this program seeks to simplify the oral antivirals access process for higher risk populations, especially in underserved communities.

For more information on the federal Test to Treat program, visit ASPR's fact sheet.

Dispensing oral antivirals

Some providers have asked if they are able to dispense oral antivirals directly from their practice without sending a prescription to be filled at a pharmacy.

Section 12-280-120(6)(a), C.R.S., states: "A practitioner may personally compound and dispense for any patient under the practitioner's care any drug that the practitioner is authorized to prescribe and that the practitioner deems desirable or necessary in the treatment of any condition being treated by the practitioner, and the practitioner is exempt from all provisions of this article 280 except section 12-280-129."

Providers who are able to directly dispense oral antivirals are strongly encouraged to enroll in the federal Test to Treat program. Please review the provider requirements below and email Victoria Giordano at victoria.giordano@state.co.us for questions and enrollment information.

Test to Treat provider requirements

• Sites must be able to provide comprehensive start-to-finish testing and treatment services to support a seamless patient experience, including:

  • COVID-19 testing on-site or via telehealth (or evaluation of at-home testing).

  • A clinical evaluation by a licensed health care provider after a positive COVID-19 test to provide prescriptions when appropriate.

  • Ability to readily dispense medications within the practice or via a co-located, affiliated, or partner outpatient pharmacy.

• Sites must be able to provide these services, regardless of the patient’s insurance status, same-day or next day.

• Sites may partner with another provider or pharmacy to offer these services.

• Sites must report their therapeutic inventory and administration twice weekly on Monday and Thursday.
   

Referring patients to Test to Treat sites

A physician referral is not required for a patient to be seen at a Test to Treat location. While Test to Treat sites are required to see patients regardless of insurance status, there may be provider evaluation or pharmacy dispensing fees. Insurance may or may not cover all or some of these fees. Find locations offering Test to Treat.

Types of antivirals

As of now, there are two oral antivirals the FDA has approved or authorized under EUA for outpatient use. Additionally, there is one intravenous antiviral, remdesivir (branded asr Veklury), which is FDA-approved for inpatient and outpatient use.

1. Paxlovid (co-packaged Nirmatrelvir and Ritonavir)

   • For treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and pediatric patients 12 years of age and older weighing at least 40 kilograms (about 88 pounds).

   • For patients who have a current clinical diagnosis of COVID-19 AND who have one or more risk factors for progression to severe COVID-19, including hospitalization or death.

   • Available by prescription only and should be initiated as soon as possible after diagnosis of COVID-19 and within five days of symptom onset.

   • Paxlovid is not approved or authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19. Patients who start Paxlovid and are subsequently admitted to the hospital may finish the prescription at the discretion of their treating provider.

   • Special attention should be given to Paxlovid contraindications which can be found in the manufacturer Dosing & Prescribing Reference Guide, particularly interactions with other medications.

   • Renal-dosed Paxlovid is an adjusted formulation that is approved for patients who have moderate renal impairment (eGFR ≥30 to <60 mL/min). Paxlovid is not recommended in patients with severe renal impairment (eGFR <30 mL/min) or in patients with severe hepatic impairment (Child-Pugh Class C). Review the “Important Dispensing Information” for health care providers.

2. Lagevrio (Molnupiravir):

   • For the treatment of mild-to-moderate COVID-19 in adults 18 years of age or older.

   • For patients who have a current clinical diagnosis of COVID-19 AND who are at high risk for progression to severe COVID-19, including hospitalization or death AND for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate.

   • Available by prescription only and should be initiated as soon as possible after diagnosis of COVID-19 and within five days of symptom onset.

   • Lagevrio is not authorized for use in patients younger than 18 years of age because it may affect bone and cartilage growth.

   • Lagevrio is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in patients hospitalized due to COVID-19 because benefit of treatment has not been observed in people when treatment started after hospitalization due to COVID-19.

   • Careful attention should be given to administration of Lagevrio in special populations (such as lactating individuals or people of childbearing age) which can be found in the FDA’s Fact Sheet For Healthcare Providers: Emergency Use Authorization for Molnupiravir.

   • Lagevrio is not recommended in pregnancy.

3. Remdesivir (Veklury):

   • For treatment of COVID-19 in adults and pediatric patients 28 days or older weighing at least 3 kilograms.

   • For patients who are hospitalized OR are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.

   • When given in the outpatient setting, Remdesivir should be administered as an intravenous (IV) infusion once a day for three days in a row and should be initiated as soon as possible after a clinical diagnosis of symptomatic COVID-19 and within seven days of symptom onset.

   • Remdesivir is not authorized or approved for the pre-exposure or post-exposure prevention of COVID-19.

   • Remdesivir (Veklury) must be ordered directly from the manufacturer.

Providers that are not part of the Test to Treat program can give patients a prescription for Paxlovid (co-packaged Nirmatrelvir and Ritonavir) or Lagevrio (molnupiravir) and direct them to a pharmacy listed in the table above.

Pharmacies that want to stock oral antivirals should email cdphe_dcphr_covidtherapeutics@state.co.us.

Providers can order remdesivir (Veklury) directly from the manufacturer.

As of now, the oral antivirals Paxlovid (co-packaged Nirmatrelvir and Ritonavir) and Lagevrio (Molnupiravir) for COVID-19 are approved or authorized for:

• People age 12 years and older for Paxlovid or age 18 years and older for molnupiravir who: 

• Have a current clinical diagnosis of COVID-19, and

• Weigh at least 40 kilograms or about 88 pounds (Paxlovid only), and

• Have had symptoms for less than 5 days, and

• Are at high risk of becoming seriously ill. People at high risk of becoming seriously ill from COVID-19 include:

  • People who are 65 years old or older.

  • People who are obese or overweight. This includes adults with a BMI of 25 or more. It also includes children under age 18 years old whose providers determine they meet the criteria.

  • Pregnant people 

    • Note that Legevrio has a warning for embryo-fetal toxicity and is not recommended during pregnancy. The effects of Paxlovid on pregnancy are unclear at this time and are being researched. Read the manufacturer Dosing & Prescribing Reference Guide for further detailed information.

  • People with certain underlying medical conditions.

As of now, the intravenous antiviral, remdesivir (Veklury), is approved for outpatient use in:

• People of ages  28 days or older who: 

• Have a current clinical diagnosis of COVID-19, and

• Weigh at least 3 kilograms, and

• Have had symptoms for less than 7 days, and

• Are at high risk of becoming seriously ill.

Guidance on inpatient use of remdesivir (Veklury) can be found on the Prescribing Information webpage. More information is available in the Emergency Use Authorization (EUA) or prescribing information for each product:

More information is available in the Emergency Use Authorization (EUA) or prescribing information for each product:

• Paxlovid approved label.

• Paxlovid EUA.

• Molnupiravir EUA .

• Remdesivir prescribing information (for adults and pediatric patients ≥28 days and ≥3 kg).

Antivirals to treat COVID-19 are not a substitute for vaccination against COVID-19. Getting vaccinated is the best way to keep from getting sick with COVID-19.

• Paxlovid (co-packaged Nirmatrelvir and Ritonavir):

  • Paxlovid consists of nirmatrelvir, which inhibits a SARS-CoV-2 enzyme to stop the virus from replicating, and ritonavir, which slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period at higher concentrations. 

  • Paxlovid is administered as three tablets (two tablets of nirmatrelvir and one tablet of ritonavir) taken together orally twice daily for five days, for a total of 30 tablets.

    • Renal Paxlovid is administered as 2 tablets (one each of nirmatrelvir and ritonavir) taken together orally twice daily for five days, for a total of 20 tablets.

• Lagevrio (molnupiravir):

  • Molnupiravir is a medication that works by introducing errors into the SARS-CoV-2 virus’ genetic code, which prevents the virus from further replicating.

  • Molnupiravir is administered as four capsules taken orally every 12 hours for five days, for a total of 40 capsules.

• Remdesivir (Velkury):

  • Remdesivir interferes with a key a SARS-CoV-2 enzyme to stop the virus from replicating.

  • When given in the outpatient setting, Remdesivir is administered as an intravenous infusion once daily for three days.

Both oral antivirals (Paxlovid and Lagevrio) are approved or authorized for use no longer than five consecutive days. Use of Remdesivir in the outpatient setting is approved for no longer than three consecutive days.

• Paxlovid (co-packaged nirmatrelvir and ritonavir):

  • Possible side effects of Paxlovid include impaired sense of taste, diarrhea, high blood pressure, and muscle aches.

  • Using Paxlovid in people with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance.

  • Ritonavir may cause liver damage, so caution should be exercised when giving Paxlovid to patients with preexisting liver diseases, liver enzyme abnormalities, or liver inflammation. It is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).

  • Using Paxlovid at the same time as certain other drugs may result in potentially significant drug interactions. 

  • Research is ongoing to understand the effects of Paxlovid in pregnant and breastfeeding people, as well as their newborns.

• Lagevrio (molnupiravir):

  • Side effects observed in clinical trials included diarrhea, nausea, and dizziness.

  • Molnupiravir is not recommended for use during pregnancy. Molnupiravir is only authorized to be prescribed to a pregnant individual after the prescribing healthcare provider has determined that the benefits of being treated with molnupiravir outweigh the risks for that individual patient and after the prescribing health care provider has communicated the known and potential benefits and the potential risks of using molnupiravir during pregnancy to the pregnant individual.

  • If the decision is made to use molnupiravir during pregnancy, the prescriber must document that the known and potential benefits and the potential risks of molnupiravir use during pregnancy, as outlined in the Fact Sheet for Patients and Caregivers, were discussed with the patient. The patient should be enrolled in the Merck Pregnancy Surveillance Program as well. 

  • Females of childbearing potential are advised to use a reliable method of birth control correctly and consistently during treatment with molnupiravir and for four days after the final dose.

  • Based on the potential for adverse reactions in the infant from Lagevrio, breastfeeding is not recommended during treatment with Lagevrio and for four days after the final dose. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for four days after the last dose of Lagevrio.

• Remdesivir (Velkury):

  • Possible side effects of remdesivir include nausea, increased ALT, and increased AST. It is recommended to perform hepatic laboratory testing in all patients. See Prescribing Information for further guidance on this topic.

  • Using remdesivir at the same time as chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data demonstrating a potential antagonistic effect.