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Frequently Asked Questions

General

Under section 564 of the Federal Food, Drug & Cosmetic Act, after a declaration by the HHS Secretary based on one of four types of determinations, FDA may authorize an unapproved product or unapproved uses of an approved product for emergency use. In issuing an EUA, FDA must determine, among other things, that based on the totality of scientific evidence available to the Agency, including data from adequate and well-controlled clinical trials, if available, it is reasonable to believe that the product may be effective in diagnosing, treating, or preventing a serious or life-threatening disease or condition caused by a chemical, biological, radiological, or nuclear agent; that the known and potential benefits, when used to treat, diagnose or prevent such disease or condition, outweigh the known and potential risks for the product; and that there are no adequate, approved, and available alternatives. Emergency use authorization is NOT the same as FDA approval or licensure.

See Full Fact Sheet for Healthcare Providers for the justification for emergency use of drugs during the COVID-19 pandemic, information on available alternatives, and additional information on COVID-19.

There is a potential risk of treatment failure due to the development of viral variants that are resistant to tixagevimab and cilgavimab. Prescribing healthcare providers should consider the prevalence of SARS-CoV-2 variants in their area, where data are available, when considering prophylactic treatment options.

For more information on neutralization data for SARS-CoV-2 variants, please see Full Fact Sheet for Healthcare Providers.

The primary analysis in the clinical efficacy study PROVENT was conducted prior to the emergence of the Omicron variant; the dominant variants in circulation at that time were Alpha, Beta, Gamma, and Delta.

Preliminary data for the neutralizing activities of tixagevimab and cilgavimab in combination against circulating Omicron subvariants are available. VLPs pseudotyped with the SARS-CoV-2 spike of Omicron BA.1 or BA.1.1 (BA.1+R346K) showed reduced neutralizing activity (132- to 183-fold or 424-fold, respectively), Omicron BA.2 showed no change in neutralizing activity (3.2-fold). Authentic Omicron BA.1 (12- to 30-fold) and BA.1.1 (176- fold) viruses showed reduced susceptibility, Omicron BA.2 showed minimal change in neutralizing activity (5.4-fold).

Data collection is ongoing to better understand how the reductions in activity seen in pseudotyped VLP assays or authentic SARS-CoV-2 assays may correlate with clinical outcomes.

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product EVUSHELDTM (tixagevimab co-packaged with cilgavimab) for the pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in 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

    • 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 to a COVID-19 vaccine(s) and/or COVID-19 vaccine component(s).

EVUSHELD may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which EVUSHELD belongs (i.e., anti-infectives).

EVUSHELD has been authorized by FDA for the emergency use described above. EVUSHELD is not FDA-approved for any use, including use for pre-exposure prophylaxis of COVID-19.

EVUSHELD is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of EVUSHELD under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

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)

LIMITATIONS OF AUTHORIZED USE

  • EVUSHELD is not authorized for use in individuals:

    • For treatment of COVID-19, or

    • For post-exposure prophylaxis of COVID-19 in individuals who have been exposed to someone infected with SARS-CoV-2

  • Pre-exposure prophylaxis with EVUSHELD is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate to severe immune compromise who may derive benefit from COVID-19 vaccination, should receive COVID-19 vaccination.

  • In individuals who have received a COVID-19 vaccine, EVUSHELD should be administered at least two weeks after vaccination.

See Full Fact Sheet for Healthcare Providers for a list of medical conditions or treatments that may result in moderate to severe immune compromise.

*For additional information please see https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html. Healthcare providers should consider the benefit-risk for an individual patient.

EVUSHELD is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis to EVUSHELD.

EVUSHELD is not authorized for treatment of COVID-19 or for post-exposure prophylaxis of COVID-19 in individuals who have been exposed to someone infected with SARS-CoV-2.

Pre-exposure prophylaxis with EVUSHELD is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended. Individuals for whom COVID-19 vaccination is recommended, including individuals with moderate to severe immune compromise who may derive benefit from COVID-19 vaccination, should receive COVID-19 vaccination.

In individuals who have received a COVID-19 vaccine, EVUSHELD should be administered at least two weeks after vaccination.

The Centers for Disease Control and Prevention have outlined clinical considerations for the use of COVID-19 vaccines, including in those who have received passive antibody products (anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma). Please refer to the CDC guidance for the latest information.

Storage & handling

Store unopened vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Discard any unused portion.

Do not freeze. Do not shake.


The expiration date for each vial can be found on each vial and on the carton.

Note the lot number, retain the product, and notify AstraZeneca immediately at 1-800-236-9933. AstraZeneca will provide further instructions on how to handle the defective product.

Manufacturing & supply

Distribution of EVUSHELD is currently being managed by the US government. Please go here to learn more.

Each 1.5 mL of tixagevimab injection contains 150 mg tixagevimab, L-histidine (2.4 mg), L-histidine hydrochloride monohydrate (3.0 mg), polysorbate 80 (0.6 mg), sucrose (123.2 mg), and Water for Injection, USP. The pH is 6.0.

Each 1.5 mL of cilgavimab injection contains 150 mg cilgavimab, L-histidine (2.4 mg), L-histidine hydrochloride monohydrate (3.0 mg), polysorbate 80 (0.6 mg), sucrose (123.2 mg), and Water for Injection, USP. The pH is 6.0.

The vial stoppers for tixagevimab and cilgavimab do not contain natural rubber latex.

The solutions for injection do not contain a preservative.

For product questions, please contact the Information Center at AstraZeneca at 1-800-236-9933, Monday through Friday, 8 AM to 8 PM ET, excluding holidays.

For order or shipping status questions, please contact C19therapies@amerisourcebergen.com.

COVID-19 monoclonal antibodies are currently being distributed by the U.S. Department of Health and Human Services in coordination with state and territorial health departments​. Healthcare providers should contact their local state or territorial health department for guidance on how to receive EVUSHELD.​ For more information on the distribution of monoclonal antibodies​ visit the HHS website, ​ State/Territory-Coordinated Distribution of COVID-19 Therapeutics.

HHS also hosts regular information sessions on the distribution and administration of COVID-19 monoclonal antibodies. To request a link to join these online meetings, email  COVID19Therapeutics@hhs.gov​.

Administration

As a prescribing healthcare practitioner, you must communicate to the patient, parent and/or caregiver information consistent with the “FACT SHEET FOR PATIENTS, PARENTS AND CAREGIVERS” and provide them with a copy of this Fact Sheet prior to administration of EVUSHELD.

Inform individuals that a higher proportion of subjects who received EVUSHELD versus placebo reported cardiovascular serious adverse events (myocardial infarctions and heart failure). Advise individuals to seek immediate medical attention if they experience any signs or symptoms suggestive of a cardiovascular event.

Serious hypersensitivity reactions, including anaphylaxis, have been observed with Human immunoglobulin G1 (IgG1) monoclonal antibodies like EVUSHELD. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur while taking EVUSHELD, immediately discontinue administration and initiate appropriate medications and/or supportive care. Clinically monitor individuals after injections and observe for at least 1 hour.

EVUSHELD has only been studied in single-dose studies. There are no safety and efficacy data available with repeat dosing. Longer term data from the study PROVENT indicated that EVUSHELD may be effective for pre-exposure prophylaxis for 6 months post-administration for pre-Omicron SARS-CoV-2 variants. However, the neutralization activity of EVUSHELD against the Omicron subvariants (BA.1, and BA.1.1 [BA.1+R346K]) versus the reference strain decreases 12- to 424-fold, and consequently the duration of protection is not known and is likely reduced. Conversely, the neutralization activity of EVUSHELD against the Omicron BA.2 subvariant versus the reference strain is minimally impacted.

Because it is unclear which SARS-CoV-2 variant or Omicron subvariant will become dominant in the United States over the next few months, the recommended timing for repeat dosing cannot be provided at this time. The Fact Sheets will be revised with repeat dosing recommendations in the near future when more data are available to determine the appropriate timing of redosing (e.g., a repeat dose with 150 mg of tixagevimab and 150 mg of cilgavimab 3 months or 6 months after the prior dose).

Safety information

The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events* and medication errors potentially related to EVUSHELD within 7 calendar days from the healthcare provider’s awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA recommends that such reports, using FDA Form 3500, include the following:

  • Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race)

  • A statement “EVUSHELD use for COVID-19 under Emergency Use Authorization (EUA)” under the “Describe Event, Problem, or Product Use/Medication Error” heading

  • Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes).

  • Patient’s preexisting medical conditions and use of concomitant products.

  • Information about the product (e.g., dosage, route of administration, NDC #).

Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods:

  • Complete and submit the report online: www.fda.gov/medwatch/report.htm

  • Complete and submit a postage-paid FDA Form 3500 and return by:

    • Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or

    • Fax to 1-800-FDA-0178, or

  • Call 1-800-FDA-1088 to request a reporting form

In addition, please provide a copy of all FDA MedWatch forms to AstraZeneca using the contact information below:

The prescribing healthcare provider and/or the provider’s designee is/are to provide mandatory responses to requests from FDA for information about adverse events and medication errors associated with EVUSHELD.

*Serious adverse events are defined as:

  • Death

  • A life-threatening adverse event;

  • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;

  • A congenital anomaly/birth defect;

  • Other important medical event, which may require a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly;

  • Inpatient hospitalization or prolongation of existing hospitalization

The most commonly reported adverse events were headache, fatigue and cough. Please see Full Fact Sheet for Healthcare Providers for more information.

In PROVENT

Adverse events were reported in 1,221 (35%) subjects receiving EVUSHELD and 593 (34%) receiving placebo. Serious adverse events were reported in 50 (1%) subjects receiving EVUSHELD and 23 (1%) receiving placebo. There was 1 adverse event reported as anaphylaxis among subjects who received EVUSHELD. The event began within minutes of EVUSHELD administration and was treated with epinephrine. The event resolved.

In STORM CHASER

Adverse events were reported in 162 (22%) subjects receiving EVUSHELD and 111 (30%) receiving placebo. SAEs were reported in 5 (<1%) subjects receiving EVUSHELD and 3 (<1%) receiving placebo.

In TACKLE

Adverse events were reported in 132 (29%) subjects receiving EVUSHELD and 163 (36%) receiving placebo. Serious adverse events were reported in 33 (7%) subjects receiving EVUSHELD and 54 (12%) receiving placebo. There were no reports of anaphylaxis and no reports of serious hypersensitivity reactions.

Please see Full Fact Sheet for Healthcare Providers for more information.

Pregnancy
There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. EVUSHELD should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.

Nonclinical reproductive toxicity studies have not been conducted with tixagevimab and cilgavimab. In a tissue cross-reactivity study assessing off-target binding of tixagevimab and cilgavimab to human fetal tissues no binding of clinical concern was observed. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, tixagevimab and cilgavimab have the potential to be transferred from the mother to the developing fetus. It is unknown whether the potential transfer of tixagevimab and cilgavimab provides any treatment benefit or risk to the developing fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Lactation
There are no available data on the presence of tixagevimab or cilgavimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EVUSHELD and any potential adverse effects on the breastfed infant from EVUSHELD.

Pediatric Use
EVUSHELD is not authorized for use in pediatric individuals under 12 years of age or weighing less than 40 kg. The safety and effectiveness of EVUSHELD have not been established in pediatric individuals. The dosing regimen is expected to result in comparable serum exposures of tixagevimab and cilgavimab in individuals 12 years of age and older and weighing at least 40 kg as observed in adults, since adults with similar body weight have been included in the trials PROVENT and STORM CHASER.

Geriatric Use
Of the 2,555 subjects in the pooled pharmacokinetics (PK) analysis (Phase I and Phase III studies), 21% (N=533) were 65 years of age or older and 3% (N=81) were 75 years of age or older. There is no clinically meaningful difference in the PK of tixagevimab and cilgavimab in geriatric subjects (≥65 years) compared to younger subjects.

Renal Impairment
Tixagevimab and cilgavimab are not eliminated intact in the urine, renal impairment is not expected to affect the exposure of tixagevimab and cilgavimab. Similarly, dialysis is not expected to impact the PK of tixagevimab and cilgavimab.

Hepatic Impairment
The effect of hepatic impairment on the PK of tixagevimab and cilgavimab is unknown.

Other Specific Populations
Based on a population PK analysis, the PK profile of tixagevimab and cilgavimab was not affected by sex, age, race, or ethnicity. Population PK model-based simulations suggest that body weight had no clinically relevant effect on the PK of tixagevimab and cilgavimab in healthy adults over the range of 36 kg to 177 kg.

Please see Fact Sheet for Healthcare Providers for the justification for emergency use of drugs during the COVID-19 pandemic, information on available alternatives, and additional information on COVID-19.

IMPORTANT SAFETY INFORMATION