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COVID-19

Monoclonal & Antiviral Therapy for Non-Hospitalized Patients


Updates

Outpatient therapeutics are widely available. Risk factors for severe COVID-19 now include: age 50+, not being up to date on COVID-19 vaccinations, and specific medical conditions and behaviors.

  • On August 15, Bebtelovimab transitioned to the commercial marketplace. CDPH has strongly recommended that remaining government supply be prioritized for uninsured and underinsured patients.
  • Providers interested in purchasing a commercial supply of Bebtelovimab can contact AmerisourceBergen. Providers will need an existing account with AmerisourceBergen to purchase Bebtelovimab.
  • Details of Medicare payment structures for Bebtelovimab can be found on the CMS website. Medicare product payment will be in the amount of $2394.00 when sites purchase the product. Note: there is NO product payment for Bebtelovimab received for free from the federal government.
  • FDA's Paxlovid Patient Eligibility Screening Checklist and Drug Interaction Tool updated with additional drugs (8-26-22)
  • California Department of Consumer Affairs allows pharmacists to prescribe Paxlovid under FDA EUA (7-11-22)
  • The My Turn landing page now has a link to the HHS Test to Treat locator.
  • Reporting requirements for Evusheld, Paxlovid, Lagevrio, bebtelovimab, have been modified. Providers should report twice weekly, by midnight on Monday and Thursday.
  • Shelf Life Extensions have been granted for certain lots of Evusheld, bebtelovimab and Paxlovid
Who should receive outpatient therapy for COVID-19?
Individuals should be considered for outpatient therapy for COVID-19 if they meet the criteria below:
  • Have mild-moderate COVID-19 illness AND
  • Have a positive SARS-CoV-2 viral test result, AND
  • Are at higher risk for progressing to severe COVID-19 and/or hospitalization.
    • Higher risk includes older persons (i.e., age 50 and older) or any age with one or more conditions on the CDC list of Underlying Medical Conditions Associated with High Risk for Severe COVID-19.
    • It is important to note that a broad group of patients qualify because the list includes common conditions such as diabetes, depression, obesity, physical inactivity, and current and former smokers among many others.
    • The likelihood of developing severe COVID-19 increases when a person has multiple comorbidities.
    • It is now recommended that providers consider the social determinants of health such as CDPH now recommends that providers consider the social determinants of health when evaluating a patient’s risk of progressing to severe COVID-19.

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

Currently recommended treatments

Four 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. They are effective against the Omicron variants.

In order of suggested use*:

  1. Paxlovid (antiviral, under EUA, taken orally for 5 days, must start within 5 days of symptom onset)
  2. Remdesivir (antiviral, FDA approved, given IV for 3 days, must start within 7 days of symptom onset)
  3. Molnupiravir and Bebtelovimab (Equal ranking) - only authorized for use if alternative COVID-19 treatment options authorized or approved by the FDA are not accessible or are not clinically appropriate.
    • Molnupiravir (antiviral, under EUA, taken orally for 5 days, must start within 5 days of symptom onset)
    • Bebtelovimab (monoclonal antibody, under EUA, given IV as single dose, must start within 7 days of symptom onset)

*From NIH COVID-19 Treatment Guidelines: Therapeutic Management of Nonhospitalized Adults With COVID-19.

See Side-by-Side Overview of Therapeutics for additional information.  (Note: Sotrovimab is no longer authorized by the FDA for use in the US due to increases in the proportion of cases caused by the Omicron sub-variant BA.2.)
Decision tools such as the IDSA roadmap are also available to assist physicians in deciding which therapeutic agent would be most appropriate for their patient. PDF

Note: Pre-exposure prophylaxis with Evusheld is recommended for individuals if they are moderately or severely immunosuppressed or are unable to be vaccinated for COVID-19 – see Pre-exposure prophylaxis - Evusheld.

1) Paxlovid

Nirmatrelvir/ritonavir (Paxlovid) — nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use. Treatment started as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.

If normal renal function, 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days. Alternate dosing is necessary for patients with reduced renal function.

Paxlovid is an oral protease inhibitor. Pfizer announced the results from a trial of 2,246 adults who received either Paxlovid or placebo. All patients had not received a COVID-19 vaccine and had not been previously infected with COVID-19. In the study, Paxlovid significantly reduced the proportion of people with COVID-19 related hospitalization or death from any cause by 88% compared to placebo among patients treated within five days of symptom onset.  

  • Currently under EUA
  • Allocations to pharmacies (with a healthcare provider prescription) and clinical sites is determined by LA County DPH. See Procuring medication for your patients.
  • Use in persons 12 years of age and older weighing at least 40 kg
  • Many drug-drug interactions
  • Paxlovid may lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
  • 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 no contraindications to therapy.
  • Clinicians who are not experienced in prescribing ritonavir-boosted drugs should refer to resources such as the EUA fact sheet for ritonavir-boosted nirmatrelvir (Paxlovid), the ISDA practice guideline on the management of drug interactions with Paxlovid, and the Liverpool COVID-19 Drug Interactions website for additional guidance.
  • The FDA revised the EUA for Paxlovid in April 2022: new additional packaging configuration to be used for dosing and dispensing in patients with moderate renal impairment; different ritonavir tablet appearance. Dear Healthcare Provider Letter
  • The FDA revised the EUA for Paxlovid in June 2022:
    • To include a number of additional drugs for which concomitant use or use immediately after discontinuation is contraindicated. These medications include drugs that are highly dependent on CYP3A for clearance as well as drugs that are potent CYP3A inducers. PAXLOVID cannot be started immediately after discontinuation of the drugs in the latter category due to the delayed offset of the recently discontinued CYP3A inducer.
    • To include new adverse reactions including hypersensitivity reactions, abdominal pain, nausea and malaise, new drug interactions and information related to rebound after Paxlovid as noted below.
  • The FDA revised the EUA for Paxlovid in July 2022
    • To expand prescribing authority to pharmacists. On 7/11 The California Department of Consumer Affairs waived any restrictions preventing pharmacists from aligning with prescribing guidance as noted in the Paxlovid EUA. Pharmacists can prescribe Paxlovid if:
      • Sufficient information is available, such as through access to health records less than 12 months old or consultation with a health care provider in an established provider-patient relationship with the individual patient, to assess renal and hepatic function; and
      • Sufficient information is available, such as through access to health records, patient reporting of medical history, or consultation with a health care provider in an established provider-patient relationship with the individual patient, to obtain a comprehensive list of medications (prescribed and non-prescribed) that the patient is taking to assess for potential drug interaction.
    • The state-licensed pharmacist should refer an individual patient for clinical evaluation (e.g., telehealth, in-person visit) with a physician, advanced practice registered nurse, or physician assistant licensed or authorized under state law to prescribe drugs, if any of the following apply:
      • Sufficient information is not available to assess renal and hepatic function.
      • Sufficient information is not available to assess for a potential drug interaction.
      • Modification of other medications is needed due to a potential drug interaction.
      • PAXLOVID is not an appropriate therapeutic option based on the authorized Fact Sheet for Healthcare Providers or due to potential drug interactions for which recommended monitoring would not be feasible.
FDA Paxlovid patient eligibility checklist PDF
Updated with additional drugs 8-26-22
Paxlovid Prescribing Provider Tool Word Document

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

Rebound after Paxlovid

Reports about patients experiencing symptom reoccurrence after completion of Paxlovid treatment have been reported. In some of these cases, patients tested negative on a direct SARS-CoV-2 viral test and then tested positive again. In light of these reports, additional analyses of the Paxlovid clinical trial data have been performed by the FDA.

Key findings include:

  • In the Paxlovid clinical trial, some patients (range 1-2%) had one or more positive SARS-CoV-2 PCR tests after testing negative, or an increase in the amount of SARS-CoV-2 detected by PCR, after completing their treatment course.
    • This finding was observed in patients treated with the drug as well as patients who received placebo.
    • Additional analyses show that most of the patients did not have symptoms at the time of a positive PCR test after testing negative, and, most importantly, there was no increased occurrence of hospitalization or death or development of drug resistance.
  • These reports do not change the conclusions from the Paxlovid clinical trial which demonstrated a marked reduction in hospitalization and death.
  • There is no evidence of benefit at this time for a longer course of treatment (e.g., 10 days rather than the 5 days recommended in the Provider Fact Sheet for Paxlovid) or repeating a treatment course of Paxlovid in patients with recurrent COVID-19 symptoms following completion of a treatment course.
  • Health care providers and patients should refer to CDC recommendations regarding patient isolation and should wear a mask and isolate if they have any symptoms regardless of whether or not they have been treated with an antiviral agent.

The FDA is continuing to review data from clinical trials and will provide additional information as it becomes available.

Cases of rebound infection after Paxlovid treatment can be reported to FDA Medwatch using Form 3500 (online or download - please also provide a copy of this form to Pfizer Inc. at fax number: 1-866-635-8337). Rebound cases can also be reported to Pfizer at https://paxaes.pfizersafetyreporting.com/#/en.

 

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

2) Remdesivir

Remdesivir (Veklury) — IV infusion for a total of 3 days initiated as soon as possible and within 7 days of symptom onset

  • FDA approved to include both inpatient and outpatient use including for pediatric patients 28 days of age and older weighing at least 3 kilograms.
  • 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.
  • 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: Press release FDA approval for children | Information for providers vekluryhcp.com | Information for patients wwwwww.veklury.com

3) Molnupiravir (equal in order of suggested use with Bebtelovimab)

Molnupiravir (Lagevrio) — 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. Merck announced results from a trial of 1,433 patients. Enrolled participants had not received a COVID-19 vaccination and had at least one risk factor associated with poor disease outcomes and symptom onset within five days prior to study enrollment. The risk of hospitalization for any cause or death through day 29 was lower with Molnupiravir (6.8%) than with placebo (9.7%), for a relative risk reduction of 30%.

  • Currently under EUA
  • 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.
  • Allocations to pharmacies (with a healthcare provider prescription) and clinical sites is determined by LA County DPH. See Procuring medication for your patients.
  • 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.
FDA Molnupiravir patient eligibility checklist PDF

Molnupiravir sample prescription:

FDA: Letter of authorization | FAQs on the EUA  | Fact sheet for health providers  |  Fact sheet for patient/caregivers

3) Bebtelovimab (equal in order of suggested use with Molnupiravir)

Bebtelovimab — single 175mg IV injection administered as soon as possible after diagnosis of COVID-19 and within 7 days of symptom onset.

  • Bebtelovimab is a monoclonal antibody therapy with EUA. It should only be used if other treatments are not available or not clinically appropriate.
  • Use in persons 12 years of age and older weighing at least 40 kg
  • 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 no contraindications to therapy
  • Requests for product can be sent to laemsadutyofficer@dhs.lacounty.gov.
  • Appears to be effective against Omicron variants

FDA: EUA Letter of Authorization | Frequently Asked Questions for Bebtelovimab | Fact sheet for health care providersFact sheet for parents/caregivers

Pre-exposure prophylaxis
Evusheld

Evusheld (Tixagevimab/cilgavimab) (AstraZeneca) - has an EUA for pre-exposure prophylaxis against COVID-19. A combination of two long-acting anti-SARS-CoV-2 monoclonal antibodies administered via intramuscular injection, Evusheld is intended to protect individuals who are unable to mount an adequate immune response to COVID-19 vaccination or are unable to receive a COVID-19 vaccine due to severe adverse reaction.

As defined in the EUA, Evusheld is authorized as a pre-exposure prophylaxis in the following:

  • Adults and pediatric individuals (12 years of age and older weighing at least 40 kg):
    • Who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and either:
      • Who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination or
      • For whom vaccination with any available COVID-19 vaccine, according to the approved or authorized schedule, is not recommended due to a history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine(s) and/or COVID-19 vaccine component(s).

According to the EUA, the medical conditions or treatments that may result in moderate to severe immune compromise and an inadequate immune response to COVID-19 vaccination include but are not limited to:

  • Active treatment for solid tumor and hematologic malignancies
  • Receipt of solid-organ transplant and taking immunosuppressive therapy
  • Receipt of chimeric antigen receptor (CAR)-T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
  • Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)
  • Advanced or untreated HIV infection (people with HIV and CD4 cell counts <200 /mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
  • Active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, Cancer chemotherapeutic agents classified as severely immunosuppressive, tumor-necrosis (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory (e.g., B-cell depleting agents)

Important information about change in dose: On 2-24-22, the FDA revised the emergency use authorization for Evusheld (tixagevimab plus cilgavimab) to increase the dose (from an initial dosing of 150 mg of tixagevimab and 150 mg of cilgavimab) to 300 mg of tixagevimab and 300 mg of cilgavimab) due to concerns about lower efficacy against certain Omicron subvariants. Health care professionals should contact patients who received the previously authorized Evusheld dose to return for repeat dosing as follows:

  • If the patient received their initial dose ≤ 3 months ago, the patient should receive an additional dose of 150 mg of tixagevimab and 150 mg of cilgavimab
  • If the patient received their initial dose > 3 months ago, the patient should receive a dose of 300 mg of tixagevimab and 300 mg of cilgavimab.

The volume of each injection for the new, higher dose will be larger (3 mL instead of 1.5 mL) This means that the injections should be limited to large muscles on the body that can accommodate this volume (e.g., the gluteal muscles)

The EUA was recently updated to include new information on hypersensitivity reactions and the risk of cross-hypersensitivity with COVID-19 vaccines and related clinical recommendations.

  • Providers are asked to consider consulting an allergist-immunologist for individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to a COVID-19 vaccine.
  • Evusheld should be administered under the supervision of a health care provider with appropriate medical support to manage severe allergic reactions
  • Patients should be observed for at least one hour post admin to monitor for hypersensitivity reactions
  • The EUA was also recently modified to recommend redosing every 6 months after the initial full dose has been completed. The repeat dosage of EVUSHELD in adults and pediatric individuals (12 years of age and older weighing at least 40 kg) is 300 mg of tixagevimab and 300 mg of cilgavimab administered every 6 months. Repeat dosing should be timed from the date of the most recent Evusheld dose.

Patients who do receive COVID-19 vaccination should wait at least 2 weeks before receiving Evusheld.

See CDC webpage for other factors to consider.

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.
  • AstraZeneca established a helpline to receive general Evusheld product information as well as guidance for ordering. Please contact the Evusheld Helpline at 1-833-EVUSHLD (1-833-388-7453) or email C19therapies@amerisourcebergen.com to learn more.
  • Providers interested in small-volume orders of 1-3 courses can also complete an order form at OrderEvusheld.com
  • Providers interested in purchasing a commercial supply of Bebtelovimab can contact AmerisourceBergen. Providers will need an existing account with AmerisourceBergen to purchase Bebtelovimab

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.

For a list of acute care hospitals that have received allocations of Bebtelovimab in Los Angeles County, visit the DHS EMS monoclonal antibody therapy webpage. Allocation is guided by local Medical Health Operational Area Coordinators (MHOACs). For questions and ordering information email laemsadutyofficer@dhs.lacounty.gov (for healthcare providers only).

For sites outside LA County, use the federal Therapeutic Distribution Locator for Providers.

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

  1. Provider Assessment
    1. Bill insurance if/when available
    2. For uninsured and underinsured, encourage use of free, low-cost care (e.g., HRSA, State-run clinics)
    3. May share cost (full fee or co-pay) with patients
  2. Testing
    1. Encourage use of ICATT sites that provide free testing
      1. Most Walgreens and CVS T2T sites are enrolled in ICATT (working towards all sites)
      2. Otherwise non-ICATT sites may charge patients
      3. Patients are able to use (free) at-home test
  3. Medication
    1. Free for all. No cost sharing with patients
  4. Dispensing Fee
    1. No cost sharing with patients

COVID-19 Therapeutics: Fees for monoclonal antibodies

  1. Provider Assessment
    1. Bill insurance if/when available
    2. For uninsured and underinsured, encourage use of free, low-cost care (e.g., HRSA, State-run clinics)
    3. May share cost (full fee or co-pay) with patients
  2. Medication
    1. Free for all. No cost sharing allowable
  3. Administration Fee
    1. Bill insurance if/when available
    2. For uninsured and underinsured, encourage use of free, low-cost care (e.g. HRSA, State-run clinics)
    3. May share cost (full fee or co-pay) with patients
  4. Details of Medicare payment structures for Bebtelovimab can be found on the CMS website. Medicare product payment will be in the amount of $2394.00 when sites purchase the product. Note: there is NO product payment for Bebtelovimab received for free from the federal government.
Resources and contact information

Contact Information

 


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Public Health has made reasonable efforts to provide accurate translation. However, no computerized translation is perfect and is not intended to replace traditional translation methods. If questions arise concerning the accuracy of the information, please refer to the English edition of the website, which is the official version.

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