Usual Adult Dose for Pre-Exposure Prophylaxis

For investigational use only

Initial Dose:

• Cilgavimab: 300 mg IM once as a single dose
• Tixagevimab: 300 mg IM once as a single dose

• If the patient received the initial dose up to 3 months ago:
• Cilgavimab: 150 mg IM once as a single dose
• Tixagevimab: 150 mg IM once as a single dose
• If the patient received the initial dose greater than 3 months ago:
• Cilgavimab: 300 mg IM once as a single dose
• Tixagevimab: 300 mg IM once as a single dose

• Cilgavimab: 300 mg IM every 6 months
• Tixagevimab: 300 mg IM every 6 months

• The US FDA issued an Emergency Use Authorization (EUA) to allow the emergency use of the unapproved product, cilgavimab co-packaged with tixagevimab, for the preexposure prophylaxis of coronavirus disease 2019 (COVID-19) in patients who are not currently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have not had a known recent exposure to someone infected with SARS-CoV-2 AND (1) who have moderate to severe immune compromise due to a medical condition or use of immunosuppressive agents/treatments and may not mount an adequate immune response to COVID-19 vaccination OR (2) for whom vaccination with any available COVID-19 vaccine (according to the approved/authorized schedule) is not recommended due to history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine and/or COVID-19 vaccine ingredients; this product is not approved by the US FDA for this or any use.
• January 26, 2023: Due to the high frequency of circulating SARS-CoV-2 variants that are nonsusceptible to this product, cilgavimab co-packaged with tixagevimab is not currently authorized in any US region; therefore, this product may not be administered for preexposure prophylaxis for prevention of COVID-19 under the EUA until further notice by the US FDA.
• Patients who already received the previously authorized initial dose (cilgavimab 150 mg and tixagevimab 150 mg) should receive an additional dose as soon as possible, with the dose based on the time elapsed since the initial dose.
• Repeat dosing should be timed from the date of the most recent dose of this product.
• No dose adjustment recommended in pregnant or lactating patients or in elderly patients.
• For additional information: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs

• Who have moderate to severe immune compromise due to a medical condition or use of immunosuppressive agents/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/authorized schedule) is not recommended due to history of severe adverse reaction to a COVID-19 vaccine and/or its ingredients

Usual Pediatric Dose for Pre-Exposure Prophylaxis

For investigational use only

12 years or older weighing at least 40 kg:
Initial Dose:

• Cilgavimab: 300 mg IM once as a single dose
• Tixagevimab: 300 mg IM once as a single dose

• If the patient received the initial dose up to 3 months ago:
• Cilgavimab: 150 mg IM once as a single dose
• Tixagevimab: 150 mg IM once as a single dose
• If the patient received the initial dose greater than 3 months ago:
• Cilgavimab: 300 mg IM once as a single dose
• Tixagevimab: 300 mg IM once as a single dose

• Cilgavimab: 300 mg IM every 6 months
• Tixagevimab: 300 mg IM every 6 months

• The US FDA issued an EUA to allow the emergency use of the unapproved product, cilgavimab co-packaged with tixagevimab, for the preexposure prophylaxis of COVID-19 in patients who are not currently infected with SARS-CoV-2 and have not had a known recent exposure to someone infected with SARS-CoV-2 AND (1) who have moderate to severe immune compromise due to a medical condition or use of immunosuppressive agents/treatments and may not mount an adequate immune response to COVID-19 vaccination OR (2) for whom vaccination with any available COVID-19 vaccine (according to the approved/authorized schedule) is not recommended due to history of severe adverse reaction (e.g., severe allergic reaction) to a COVID-19 vaccine and/or COVID-19 vaccine ingredients; this product is not approved by the US FDA for this or any use.
• January 26, 2023: Due to the high frequency of circulating SARS-CoV-2 variants that are nonsusceptible to this product, cilgavimab co-packaged with tixagevimab is not currently authorized in any US region; therefore, this product may not be administered for preexposure prophylaxis for prevention of COVID-19 under the EUA until further notice by the US FDA.
• Patients who already received the previously authorized initial dose (cilgavimab 150 mg and tixagevimab 150 mg) should receive an additional dose as soon as possible, with the dose based on the time elapsed since the initial dose.
• Repeat dosing should be timed from the date of the most recent dose of this product.
• No dose adjustment recommended in pregnant or lactating patients.
• For additional information: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs

• Who have moderate to severe immune compromise due to a medical condition or use of immunosuppressive agents/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/authorized schedule) is not recommended due to history of severe adverse reaction to a COVID-19 vaccine and/or its ingredients

Renal Dose Adjustments

Renal dysfunction: No adjustment recommended

Liver Dose Adjustments

Data not available

Precautions

CONTRAINDICATIONS:
Previous severe hypersensitivity reactions (including anaphylaxis) to either active component or to any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years; this product is not authorized for use in pediatric patients weighing less than 40 kg or younger than 12 years.

Dialysis

Data not available

Other Comments

January 26, 2023: Due to the high frequency of circulating SARS-CoV-2 variants that are nonsusceptible to this product, cilgavimab co-packaged with tixagevimab is not currently authorized in any US region; therefore, this product may not be administered for preexposure prophylaxis for prevention of COVID-19 under the EUA until further notice by the US FDA.

Administration advice:

• Cilgavimab and tixagevimab should be administered by a qualified health care provider with appropriate medical support to manage severe hypersensitivity reactions.
• Administer cilgavimab and tixagevimab as 2 separate, consecutive IM injections.
• Administer the IM injections at different injection sites, preferably each in a separate gluteal muscle, 1 after the other; ensure the administration sites are appropriate for the volume to be injected.
• Clinically monitor patients after injections and observe for at least 1 hour.

• Unopened vials: Store in refrigerator at 2C to 8C (36F to 46F) in original carton to protect from light; do not freeze; do not shake.
• Prepared syringes: Should administer immediately; if immediate administration is not possible, total storage time (from vial puncture to administration) must not exceed 4 hours, in a refrigerator at 2C to 8C (36F to 46F) or at room temperature up to 25C (77F).

• Cilgavimab and tixagevimab must be prepared by a qualified health care provider.
• The Fact Sheet for Health Care Providers should be consulted.

• The Fact Sheet for Health Care Providers should be consulted.
• This product may only be prescribed for an individual patient by health care professionals licensed/authorized under state law to prescribe drugs in the therapeutic class to which this product belongs (i.e., anti-infectives).
• The recommendations for dosing are based on the totality of the scientific evidence (including clinical pharmacology, antiviral activity, and clinical trial data).
• This product has only been studied for the prophylaxis of COVID-19 at the previously authorized dose (cilgavimab 150 mg and tixagevimab 150 mg).
• No data are available in a prophylaxis setting for the modified dose (cilgavimab 300 mg and tixagevimab 300 mg), but clinical safety of this dose is supported by safety data from a treatment study in patients with mild to moderate COVID-19.
• Limited safety and no efficacy data are available with repeat dosing.
• There is no adequate, approved, and available alternative to this product, cilgavimab co-packaged with tixagevimab, for the preexposure prophylaxis of COVID-19 in patients who may not mount an adequate immune response to COVID-19 vaccination or for whom COVID-19 vaccination is not recommended due to history of severe adverse reaction to a COVID-19 vaccine or its ingredients.
• ClinicalTrials.gov should be consulted for information on clinical trials testing this product for the prophylaxis of COVID-19.
• LIMITATIONS OF AUTHORIZED USE:
• This product is not authorized for the treatment of COVID-19.
• This product is not authorized for postexposure prophylaxis of COVID-19 in patients exposed to someone infected with SARS-CoV-2.
• This product is authorized for use only when the combined frequency of nonsusceptible variants nationally is 90% or less, based on available information (including variant susceptibility to this product and national variant frequencies); US FDA will monitor conditions to determine whether use is consistent with the scope of authorization, referring to available information (including variant susceptibility and US CDC variant frequency data).
• Preexposure prophylaxis with this product is not a substitute for vaccination in patients for whom COVID-19 vaccination is recommended; such patients (including those with moderate to severe immune compromise who may derive benefit from COVID-19 vaccination), should receive COVID-19 vaccination.
• In patients who have received a COVID-19 vaccine, this product should be administered at least 2 weeks after vaccination.
• 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
• Hematologic malignancies associated with poor responses to COVID-19 vaccines regardless of current treatment status (e.g., chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, acute leukemia)
• Receipt of solid-organ transplant or an islet 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 immunosuppressive therapy)
• Moderate or severe primary immunodeficiency (e.g., common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome)
• Advanced or untreated HIV infection (patients with HIV and CD4 counts less than 200/mm3, history of AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
• Active treatment with high-dose corticosteroids (i.e., at least 20 mg prednisone or equivalent per day when administered for at least 2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, and biologic agents that are immunosuppressive or immunomodulatory (e.g., B-cell depleting agents)

• Read the Fact Sheet for Patients, Parents, and Caregivers.
• You will need to receive additional doses of this product every 6 months if ongoing protection is needed.
• Certain SARS-CoV-2 viral variants may not be neutralized by monoclonal antibodies (such as the components of this product); therefore, this product may not prevent COVID-19 due to these SARS-CoV-2 viral variants. If signs/symptoms of COVID-19 occur, test for COVID-19 and seek medical attention, including starting COVID-19 therapy as appropriate.
• Seek immediate medical attention if any signs/symptoms suggestive of a cardiovascular event occur.