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Evusheld, a COVID-19 prevention medication manufactured by AstraZeneca, received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) on Dec. 8, 2021. It is not intended to replace a COVID-19 vaccine series for anyone who is eligible. It is a protective option for those who cannot receive the COVID vaccine or who may not mount an adequate immune response to the vaccine—specifically those with a history of severe adverse reactions or allergic reaction to vaccines or those who are immunocompromised due to medication or a medical condition.

What is Evusheld?

Evusheld is a combination of two human monoclonal antibodies (tixagevimab and cilgavimab) that are co-packaged and administered together. It’s the first monoclonal antibody therapy intended to work as a pre-exposure prophylaxis for people who are not yet infected with COVID-19. “The previous monoclonal antibodies, (bamlanivimab and etesevimab, REGEN-COV [casirivimab and imdevimab], and sotrovimab), were authorized for … treatment of COVID-19,” says Javeed Siddiqui, MD, MPH, the co-founder and chief medical officer at TeleMed2U in California. Bamlanivimab and etesvimab, and REGEN-COV, also held EUAs for post-exposure prophylaxis.

Monoclonal antibodies (mAbs) are laboratory-produced molecules that restore, improve, or replicate the immune system’s defenses against pathogens. Evusheld works by targeting the surface spike protein of the SARS-CoV-2 virus, thereby preventing it from interacting with the human ACE2 receptor, which is required for virus attachment and incorporation into human cells.

So far, the combination monoclonal preventive treatment appears to be effective against all known variants of the novel coronavirus—including Delta and Omicron variants, although the neutralizing activity is decreased against Omicron. “After receiving Evusheld, if you do test positive for COVID, the prevailing thought is that your immune system is primed and much more prepared to fight a COVID-19 infection,” says Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital in New York. “If you do get infected, you will likely have a mild infection or may even be asymptomatic.”

Dosage

The recommended dosage of Evusheld is 150 mg of tixagevimab and 150 mg of cilgavimab. “Each antibody should be administered as intramuscular injections at separate sites on the body,” says Dr. Siddiqui. The gluteal muscles are the preferred sites of injection, and patients should be monitored for a minimum of one hour after the pair of shots are given. Evusheld can be administered to the same patient once every six months.

Evusheld is authorized for use in adults and adolescents over 12 years of age who weigh a minimum of 88 pounds. It is meant to be administered before exposure to or infection with COVID-19 and can be given in an outpatient setting. “The antibodies should not be used for treatment or post-exposure prophylaxis of COVID-19, or within two weeks after administration of a COVID-19 vaccine,” Dr. Siddiqui says. However, an antibody test is not required before receiving Evusheld.

Side effects

In clinical trials of tixagevimab and of cilgavimab, 35% of those who received the drug experienced mild to moderate adverse reactions, similar to the amount of those in the placebo group. The most common side-effects reported were:

Headache
Fatigue
Cough

Overall, in the clinical trials, the medication was tolerated well. The following serious adverse effects were rare, affecting only 0.6% of those who received the drug:

Coronary artery disease or myocardial ischemia
Myocardial infarctions
Cardiac failure
Arrhythmia
Other (cardiomegaly, cardiomyopathy, and cardio-respiratory arrest)

It’s important to note that all of the participants who experienced a cardiac event had cardiac risk factors or a history of cardiac disease at baseline. Because the medication is so new, it is not known at this time whether side effects can be minimized.

In the trial, people who received Evusheld had a 77% reduction in risk of contracting COVID-19 compared with those who received a placebo. “While Evusheld does not completely remove the risk of contracting COVID-19,” Dr. Glatter says, “it helps to blunt the potentially serious clinical course that could result in persons who are immunocompromised.” That means it decreases the risk of developing severe COVID-19.

Contraindications and restrictions

Evusheld is not authorized for use in pediatric patients under the age of 12 or those who weigh less than 40 kilograms (88 pounds). In clinical trials, there was no increase in adverse events among those over 65 years old or over 75 years old, so no limitations have been placed on older patients.

To date, there is no data on the safety of Evusheld in those who are pregnant or breastfeeding. At present, the FDA recommends that the medication only be used when the benefits outweigh the risk to the mother and the fetus.

Evusheld is approved for use in patients with mild to moderate renal impairment. Currently, no contraindications have been identified for patients with severe renal impairment or for patients on dialysis. There are no specific recommendations for those with hepatic impairment at this time.

When will it be available?

Although Evusheld is available now, many large health systems in the U.S. have limited supplies. In December 2021, the U.S. government purchased 700,000 doses of Evusheld.

On Jan. 12, 2022, AstraZeneca announced that the U.S. government agreed to purchase 500,000 additional doses of Evusheld, for a total of 1.2 million.

Healthcare providers are reaching out to immunocompromised patients who are eligible to receive the injections, working to get the COVID-19 prevention to the people who need it most and to distribute the limited doses in the most equitable way possible. “Some institutions have implemented a lottery that prioritizes the most immunocompromised patients to help make distribution fair,” Dr. Glatter says. In instances of limited availability, priority should be given to those who are at highest risk of severe SARS-CoV-2.

Where to buy Evusheld

Allocation is handled primarily through the local health department. “Currently, there is limited information on availability and access to Evusheld will be varied,” says Dr. Siddiqui.

Those who receive Evusheld must receive one hour of post-administration observation. “Therefore, clinics, hospitals and out-patient infusion centers are most likely best equipped to offer this medication,” Dr. Sidiqqui explains.

How much does Evusheld cost?

Because the federal government has purchased a supply of monoclonal antibody doses, there is typically no cost to the patient for the injection itself, according to the U.S. Department of Health and Human Services. However, patients may be charged an administration fee by their providers. When in doubt, check with your insurance company first.

Currently, Medicare is covering the costs of injection and administration. Patients without insurance should also ask their treatment facility if they will be responsible for any costs.

Other COVID treatment updates

Evusheld is not a treatment and therefore will not be used in patients who are currently infected with coronavirus. The following COVID-19 therapeutics are available for nonhospitalized patients with mild to moderate cases of COVID-19 who are at high risk of serious disease progression, according to a statement updated by the National Institute of Health’s COVID-19 Treatment Guidelines Panel on January 19, 2022. They are ranked in order of recommendation, with Pavloxid being the favored treatment. Molnupiravir should be the last treatment considered because in trials of the drug, it only reduced the risk of hospitalization or death by 30%, compared to 88% with Pavloxid, 87% with Remdesivir, and 70%-85% with Sotrovimab.

Paxlovid (ritonavir-boosted nirmatrelvir): Dosage is 300 mg of nirmatrelvir and 100mg of ritonavir, taken orally twice daily for five days as soon as possible within five days of symptom onset. Because Pavloxid has significant drug interactions, providers must review their patients’ medications before prescribing the treatment and may need to utilize alternatives if severe interactions exist.
Sotrovimab: Dosage is a 500 mg intravenous antibody infusion administered as soon as possible up to 10 days after symptom onset. Patients must be monitored for an hour after receiving the infusion in case of severe allergic reaction. Unlike Evusheld, which is a preventive therapy, sotrovimab is a monoclonal antibody treatment for mild to moderate COVID-19 in those patients at risk for progressing to severe disease.
REGEN-COV: Like sotrovimab, REGEN-COV is a monoclonal antibody treatment for COVID-19 whereas Evusheld is a preventive therapy. Dosage is 600 mg of casirivimab and 600 mg of imdevimab administered via IV or subcutaneous injection. On Jan. 24, 2022, the FDA amended REGEN-COV’s EUA to restrict its use in regions of the United States where exposure is likely due to a variant not susceptible to this treatment, such as the Omicron variant. Given the predominance of the Omicron variant across the U.S., REGEN-COV is not currently authorized for use.
Remdesivir: Dosage is intravenous infusion for three consecutive days (200 mg on day 1 followed by 100 mg on days 2 and 3) administered in a setting such as a medical center as soon as possible up to seven days of symptom onset. Patients must be monitored for an hour after receiving the infusion in case of severe allergic reaction.
Molnupiravir: Dosage is 800 mg taken orally twice a day for five days as soon as possible within five days of symptom onset. The drug is not recommended in pregnant individuals.

Eligible patients can receive the antiviral treatments Pavloxid, sotrovimab, remdesivir, and molnupiravir free of charge from the federal government.

On Feb. 11, 2022, the FDA issued an EUA for yet another monoclonal antibody for treatment of mild to moderate COVID-19, which retains activity against the Omicron variant, known as bebtelovimab. The dose is a single 175 mg injection, which can be administered in those at high risk of progressing to severe disease within seven days of symptom onset.