Therapeutic Options for COVID-19 Patients

• Currently the preferred first-line therapy for treatment of eligible patients with COVID-19. Refer to NIH: COVID-19 Treatment Guidelines: Therapeutic Management of Nonhospitalized Adults with COVID-19.
• Combination of a SARS-CoV-2 protease inhibitor (nirmatrelvir) with ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor. Ritonavir acts as a pharmacological booster to increase the levels of nirmatrelvir.
• Authorized for the treatment of mild-to-moderate COVID-19 in patients at high risk for severe illness from COVID-19.
• For information on medical conditions and factors associated with increased risk, visit CDC: Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19. This list is not exhaustive and providers should consider the risks and benefits for individual patients.
• Treatment must be started within five days of symptom onset and is given as a five-day treatment course.
• Efficacy: In the EPIC-HR trial (Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults, New England Journal of Medicine), ritonavir-boosted nirmatrelvir (Paxlovid) reduced the risk of hospitalization or death by 89% compared to placebo in non-hospitalized, high-risk, unvaccinated adults with laboratory-confirmed SARS-CoV-2 infection.

The following are limitations to the use of Paxlovid:

• Paxlovid is not authorized for use in patients younger than 12 years.
• Paxlovid is not recommended for use in patients with severe renal impairment (GFR<30ml/min) or hepatic impairment (Child-Pugh Class C).
• For patients with moderate renal impairment (GFR 30-60ml/min), the dose of nirmatrelvir should be reduced from 300mg to 150mg (refer to FDA: Fact Sheet for Providers below).

Due to the co-administration with ritonavir, it is critical to evaluate the patient medication regimen for potentially serious drug-drug interactions prior to prescribing Paxlovid.

• Providers should review the patient’s medication regimen (including over-the-counter medications, supplements, and any recreational drugs) for potentially serious drug interactions.
• Interactions may be checked using the University of Liverpool COVID-19 Drug Interactions interactive webpage.

COVID-19 rebound:

• Rebound is defined as experiencing recurrence of symptoms and/or SARS-CoV-2 test positivity after initial resolution.
• Rebound has been observed in patients receiving other antiviral treatment for COVID-19 besides Paxlovid as well as in patients receiving no treatment.
• Studies suggest patients with rebound typically have mild symptoms and have an extremely low probability of developing severe COVID-19.
• Paxlovid continues to be recommended for early-stage treatment of COVID-19 in patients at high risk for severe disease and should not be withheld solely due to concerns about rebound.
• Patients should be counseled to follow isolation guidance if they develop rebound. More information for providers is available at CDC Health Alert Network: COVID-19 Rebound After Paxlovid Treatment.

References:

• FDA: Fact Sheet for Healthcare Providers: Emergency Use Authorization for Paxlovid (PDF)
• FDA: Frequently Asked Questions on the EUA for Paxlovid

• Currently recommended as an alternative therapy for use when the preferred therapies (Paxlovid or outpatient remdesivir, see below) are not available, feasible to use, or clinically appropriate. See NIH COVID-19 Treatment Guidelines: Therapeutic Management of Nonhospitalized Adults with COVID-19.
• Oral nucleoside analogue that inhibits SARS-CoV-2 replication by inducing viral mutagenesis.
• Authorized for the treatment of mild to moderate COVID-19 in patients at high risk for severe illness from COVID-19.
• For information on medical conditions and factors associated with increased risk, see CDC: Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19. This list is not exhaustive and providers should consider the risks and benefits for individual patients.
• Treatment must be started within five days of symptom onset and is given as a five-day treatment course.
• Efficacy: In the MOVe-OUT trial (Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, New England Journal of Medicine) molnupiravir reduced the rate of hospitalization or death by 30% compared to placebo in non-hospitalized, unvaccinated, high-risk adults with laboratory-confirmed SARS-CoV-2 infection.

The following are limitations to the use of molnupiravir.

• Molnupiravir is not authorized for use in patients younger than 18 years.
• Molnupiravir is not recommended for use in pregnancy. Patients of childbearing potential should be advised to use effective contraception correctly and consistently, as applicable, for the duration of treatment and for four days after the last dose of molnupiravir.
• Molnupiravir is not recommended for use while breastfeeding. Breastfeeding is not recommended during treatment and for four days after the last dose of molnupiravir. 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 molnupiravir.

References:

• FDA: Fact Sheet for Health Care Providers: Emergency Use Authorization for Molnupiravir (PDF)
• FDA: Frequently Asked Questions on the EUA for Lagevrio (molnupiravir)

• Currently recommended as a preferred therapy for use in eligible patients if Paxlovid is not clinically appropriate (e.g., due to significant drug-drug interactions). See NIH COVID-19 Treatment Guidelines: Therapeutic Management of Nonhospitalized Adults with COVID-19.
• Inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase which interrupts viral replication.
• Previously approved only in hospitalized patients but expanded approval to outpatient use in January 2022.
• In the PINETREE trial (Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients, New England Journal of Medicine), three consecutive days of IV remdesivir resulted in an 87% reduction in the risk of hospitalization or death compared to placebo in non-hospitalized, high-risk, unvaccinated patients with laboratory-confirmed SARS-CoV-2 infection.
• Treatment should be initiated as soon as possible and within seven days of symptom onset.

• Due to logistical constraints on administration, outpatient remdesivir is not widely available.
• Locations offering outpatient remdesivir have been added to the HHS/ASPR Covid-19 Therapeutics Locator; however, since remdesivir is not being distributed by the federal government, facilities must opt in to appearing on the locator and thus this list may not be comprehensive.
• Providers should check with their nearest hospital or infusion center to see whether outpatient remdesivir treatment can be arranged. Infectious disease consultation may be required.

• Gilead: Highlights of Prescribing Information for Remdesivir (PDF)

COVID-19 convalescent plasma (CCP) is human plasma obtained from donors who have recovered from COVID-19. It may contain antibodies to SARS-CoV-2 that suppress viral replication. As of Dec. 28, 2021, CCP with high titers of anti-SARS-CoV-2 antibodies is currently authorized for the treatment of COVID-19 in patients with immunosuppressive disease or who are receiving immunosuppressive treatment. It is authorized for use in either the outpatient or the inpatient setting. This authorization is based on the totality of the scientific evidence available that suggests the potential benefits of CCP outweigh the potential risks when used for this indication. However, additional data from randomized controlled clinical trials are needed.

Plasma donations must be tested by registered or licensed blood establishments for high titers of anti-SARS-CoV-2 antibodies as a manufacturing step to determine suitability before release, using one of the tests and qualifying results listed in the FDA EUA.

Clinical dosing may first consider starting with one high titer CCP unit (about 200mL), with administration of additional high titer CCP units based on the prescribing physician’s judgment and the patient's clinical response.

• FDA: Fact Sheet for Healthcare Providers: Emergency Use Authorization of COVID-19 Convalescent Plasma for Treatment of COVID-19

Tocilizumab is an interleukin (IL)-6 inhibitor that can be used in hospitalized patients with progressive severe or critical COVID-19 illness that demonstrate elevated markers of inflammation. For a more complete review of the evidence, benefits/harms and treatment criteria, refer to the National Institutes of Health (NIH) and Infectious Disease Society of America (IDSA) COVID-19 treatment guidelines below:

• IDSA Guidelines on the Treatment and Management of Patients with COVID-19
  Last updated March 1, 2023
   
• NIH COVID-19 Treatment Guidelines: Interleukin-6 Inhibitors
  Last updated Jan. 26, 2023

Baricitinib is a Janus kinase (JAK) inhibitor that can be used in hospitalized patients with severe COVID-19 disease and elevated inflammatory markers, but not requiring mechanical ventilation. It can also be given in conjunction with remdesivir to hospitalized patients with severe disease who are unable to receive corticosteroids due to a contraindication. For a more complete review of the evidence, benefits/harms and treatment criteria, refer to the NIH and IDSA COVID-19 treatment guidelines below:

• IDSA Guidelines on the Treatment and Management of Patients with COVID-19
  Last updated March 1, 2023
   
• NIH COVID-19 Treatment Guidelines: Kinase Inhibitors: Janus Kinase Inhibitors, and Bruton's Tyrosine Kinase Inhibitors
  Last updated Aug. 8, 2022