Updated December 1, 2022
The following treatment recommendations are intended to assist Orange County providers in making COVID-19 treatment decisions.
The National Institutes of Health (NIH) COVID-19 Treatment Guidelines remains the recommended source for current guidance on the treatment and the use of COVID-19 therapeutics and prophylaxis.
Availability of Therapeutics
COVID-19 therapeutics are widely available. Providers and patients should continue to use the Therapeutic Distribution Locator to identify local availability.
On November 30, 2022, the U.S. Food and Drug Administration (FDA) announced that bebtelovimab is no longer authorized for emergency use in the U.S. The rational being that this agent is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1, and based on CDC Nowcast data these subvariants represent >50% of those circulating in all regions of the county.
On November 10, 2022, NIH released COVID-19 Treatment Guidelines Panel’s Statement on Omicron Subvariants, Pre-Exposure Prophylaxis, and Therapeutic Management of Nonhospitalized Patients With COVID-19. SARS-CoV-2 Omicron subvariants BQ.1 and BQ.1.1 are likely to be resistant to bebtelovimab and the subvariants BA.4.6, BA.2.75.2, BA.5.2.6, BF.7, BQ.1, and BQ.1.1 are likely to be resistant to tixagevimab plus cilgavimab (Evusheld). Tixagevimab plus cilgavimab are the only agents authorized by the Food and Drug Administration for use as COVID-19 PrEP in people who are not expected to mount an adequate immune response to COVID-19 vaccination or those with contraindications for COVID-19 vaccines. In the absence of an alternative option for PrEP, the Panel continues to recommend the use of tixagevimab plus cilgavimab as PrEP for eligible individuals.
Providers should be aware of available data on subvariants. Due to lags associated with specimen receipt and sequencing, current information about SARS-CoV-2 variants is best based on projections from CDC’s COVID Data Tracker Nowcast, and California Department of Public Health’s CALCAT provides variant projections for Southern California.
Recommendations for Treatment of Nonhospitalized patients with COVID-19: NIH Guidelines
The National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel is regularly updating its recommendations for Therapeutic Management of Nonhospitalized Adults With COVID-19. The panel recommends using one of the following therapeutics (listed in order of NIH preference, with the NIH panel’s comments on each product included):
- Nirmatrelvir 300 mg with ritonavir 100 mg (Paxlovid) - For information on dosing, administration, and safety, including information on drug interactions for Paxlovid review the FDA Fact Sheet for Healthcare Providers Emergency Use Authorization (EUA) of PAXLOVID.
- Ritonavir-boosted nirmatrelvir (Paxlovid) has significant and complex drug-drug interactions, primarily due to the ritonavir component of the combination.
- Before prescribing ritonavir-boosted nirmatrelvir (Paxlovid), clinicians should carefully review the patient’s concomitant medications, including over-the-counter medications and herbal supplements, to evaluate potential drug-drug interactions. See the Panel’s statement on the drug-drug interactions for ritonavir-boosted nirmatrelvir (Paxlovid) for details.
- For those with moderate renal impairment (eGFR ≥30 to <60 mL/min) a 150 mg Nirmatrelvir with 100 mg ritonavir dose pack is now available.
- Remdesivir (Veklury) - For information on dosing administration and safety and use of remdesivir for both pediatric and adult populations review the FDA approved package insert.
- Remdesivir should be administered in a setting where severe hypersensitivity reactions, such as anaphylaxis, can be managed. Patients should be monitored during the infusion and observed for at least 1 hour after infusion.
- Bebtelovimab - no longer authorized for use. The FDA recommends all bebtelovimab product be retained in the event that SARS-CoV-2 variants susceptible to bebtelovimab, which are currently circulating at lower prevalence, become more prevalent in the future in the United States. Retained product must be appropriately held in accordance with storage conditions detailed in the authorized Fact Sheet for Health Care Providers and the Letter of Authorization for bebtelovimab.
- Molnupiravir (Legevrio) - For information on administration, dosing, and safety of Molnupiravir (Legevrio) review the Fact Sheet for Healthcare Providers: Emergency Use Authorization (EUA) for Legevrio (molnupiravir).
- The FDA EUA states that molnupiravir (Legevrio) is not recommended for use in pregnant patients due to concerns of fetal toxicity observed during animal studies. However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir (Legevrio) therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy.
- There are no data on the use of molnupiravir (Legevrio) in patients who have received COVID-19 vaccination, and the risk-to-benefit ratio is likely to be less favorable because of the lower efficacy of this drug.
Recommendations for Pre-Exposure Prophylaxis for COVID-19
Tixagevimab plus cilgavimab (Evusheld) - For information on dosing, administration and safety of Evusheld review the Fact Sheet for Healthcare Providers: Emergency Use Authorization for Evusheld.
Evusheld is authorized for use as SARS-CoV-2 PrEP for individuals who have moderate to severe immunocompromising conditions that may result in an inadequate immune response to COVID-19 vaccination. Unlike anti-SARS-CoV-2 agents used for treatment, tixagevimab plus cilgavimab (Evusheld) is not authorized for use in unvaccinated individuals unless full vaccination is not possible due to a history of severe allergic reaction to the COVID-19 vaccine. Generally speaking, those who qualify for PrEP because of allergy to the vaccine or contraindication to vaccination are less likely to suffer severe consequences, unless they are also moderately to severely immunocompromised.
Please review The COVID-19 Treatment Guidelines Panel’s Interim Statement on Patient Prioritization for Outpatient Anti-SARS-CoV-2 Therapies or Preventive Strategies When There Are Logistical or Supply Constraints if facing issues limited supplies of medications.