Updated December 31, 2021
The following treatment recommendations are intended to assist Orange County providers in making treatment decisions in the context of the emergence of the omicron variant and the national COVID-19 therapeutics shortage.
There are multiple anti-SARS-CoV-2 products that can be used for treatment or prophylaxis of COVID-19 that have received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA). However, providers should be aware of factors that have important implications for use of these products in patient care:
- Initial supplies of these products will be extremely limited and will be directed by the federal government for the next several weeks.
- Area pharmacies that are designated by the Department of Health and Human Services to receive Paxlovid and Molnupiravir can be found here.
- The Omicron variant, which is now causing a significant proportion of COVID-19 in Orange County, includes numerous mutations in the spike protein and is predicted to have markedly reduced susceptibility to several anti-SARS-CoV-2 monoclonal antibody products. As of December 31, 2021, local surveillance data indicates that Delta VOC still represents a significant proportion of infections in Orange County.
The California Department of Public Health (CDPH) released Health Alerts on Paxlovid and Molnupiravir which include guidance on prioritizing patients for these drugs as well as ethical considerations for treatment given supply limitations.
Recommendations for Treatment of Nonhospitalized patients with COVID-19: NIH Guidelines
On December 30, 2021, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines the Panel released a Statement on Therapies for High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19. In this guidance, 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) orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg.
- 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.
- Sotrovimab 500 mg as a single IV infusion, administered as soon as possible and within 10 days of symptom onset in those aged ≥12 years and weighing ≥40 kg who live in areas with a high prevalence of the Omicron VOC.
- If the Delta VOC still represents a significant proportion of infections in the region and other options are not available or are contraindicated, patients can be offered bamlanivimab plus etesevimab or casirivimab plus imdevimab, with the understanding that this treatment would be ineffective if they are infected with the Omicron VOC. (Note: as of December 31, 2021, local surveillance data indicates that Delta VOC still represents a significant proportion of infections in Orange County.)
- Sotrovimab 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.
- Remdesivir 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg.
- Because remdesivir requires IV infusion for 3 consecutive days, there may be logistical constraints to administering remdesivir in many settings.
- Remdesivir is currently approved by the FDA for use in hospitalized individuals, and outpatient treatment would be an off-label indication.
- 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.
- Molnupiravir 800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY when none of the above options can be used.
- The FDA EUA states that molnupiravir is not recommended for use in pregnant patients due to concerns about the instances 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 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 in patients who have received COVID-19 vaccines, and the risk-to-benefit ratio is likely to be less favorable because of the lower efficacy of this drug.Initial Distribution of Paxlovid and Molnupiravir
Recommendations for Pre-Exposure Prophylaxis for COVID-19
Tixagevimab plus cilgavimab (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.
NIH guidance for prioritizing Anti-SRS-CoV-2 treatment therapies (listed above) or preventive therapies (including Evusheld) can be found here.
Due to limited supply, a few Orange County hospitals have been allocated a limited number of Evusheld doses to provide protection for their highest-risk patients. A list of hospitals that have received product can be found here.