DailyMed Label: Casirivimab

DailyMed Label: Casirivimab

2022

DailyMed Prescription

Casirivimab

Casirivimab

Regeneron Pharmaceuticals, Inc.

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-026

NDC: 61755-024

NDC: 61755-027

NDC: 61755-025

NDC: 61755-039

NDC: 61755-035

NDC: 61755-036

NDC: 61755-037

NDC: 61755-038

NDC: 61755-039

NDC: 61755-039

NDC: 61755-042

NDC: 61755-045

NDC: 61755-042

NDC: 61755-045

NDC: 61755-042

NDC: 61755-045

NDC: 61755-026

NDC: 61755-026

NDC: 61755-024

NDC: 61755-024

NDC: 61755-027

NDC: 61755-027

NDC: 61755-025

NDC: 61755-025

NDC: 61755-039

NDC: 61755-039

NDC: 61755-035

NDC: 61755-035

NDC: 61755-036

NDC: 61755-036

NDC: 61755-037

NDC: 61755-037

NDC: 61755-038

NDC: 61755-038

NDC: 61755-042

NDC: 61755-042

NDC: 61755-045

NDC: 61755-045

Casirivimab, a human immunoglobulin G-1 (IgG1) monoclonal antibody (mAb), is a covalent heterotetramer consisting of 2 heavy chains and 2 light chains produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture and has an approximate molecular weight of 145.23 kDa. Casirivimab injection is a sterile, preservative-free, clear to slightly opalescent and colorless to pale yellow solution in a vial for subcutaneous use or intravenous infusion after dilution available as a 300 mg/2.5 mL (120 mg/mL) or 1,332 mg/11.1 mL (120 mg/mL) solution and must be administered with imdevimab. The vial stoppers are not made with natural rubber latex. Casirivimab: Each 2.5 mL of solution contains 300 mg of casirivimab, L-histidine (1.9 mg), L-histidine monohydrochloride monohydrate (2.7 mg), polysorbate 80 (2.5 mg), sucrose (200 mg), and Water for Injection, USP. The pH is 6.0. Casirivimab: Each 11.1 mL of solution contains 1,332 mg of casirivimab, L-histidine (8.3 mg), L-histidine monohydrochloride monohydrate (12.1 mg), polysorbate 80 (11.1 mg), sucrose (888 mg), and Water for Injection, USP. The pH is 6.0. Imdevimab, a human IgG1 mAb, is a covalent heterotetramer consisting of 2 heavy chains and 2 light chains produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture and has an approximate molecular weight of 144.14 kDa. Imdevimab injection is a sterile, preservative-free, clear to slightly opalescent and colorless to pale yellow solution in a vial for subcutaneous use or intravenous infusion after dilution available as a 300 mg/2.5 mL (120 mg/mL) or 1,332 mg/11.1 mL (120 mg/mL) solution and must be administered with casirivimab. The vial stoppers are not made with natural rubber latex. Imdevimab: Each 2.5 mL of solution contains 300 mg of imdevimab, L-histidine (1.9 mg), L-histidine monohydrochloride monohydrate (2.7 mg), polysorbate 80 (2.5 mg), sucrose (200 mg), and Water for Injection, USP. The pH is 6.0. Imdevimab: Each 11.1 mL of solution contains 1,332 mg of imdevimab, L-histidine (8.3 mg), L-histidine monohydrochloride monohydrate (12.1 mg), polysorbate 80 (11.1 mg), sucrose (888 mg), and Water for Injection, USP. The pH is 6.0. REGEN-COV (casirivimab and imdevimab solution) injection is a sterile, preservative-free, clear to slightly opalescent, and colorless to pale yellow 10 mL solution in a vial for intravenous infusion after dilution. The vial stoppers are not made with natural rubber latex. Each 10 mL of solution contains 600 mg of casirivimab, 600 mg of imdevimab, L-histidine (7.4 mg), L-histidine monohydrochloride monohydrate (10.9 mg), polysorbate 80 (10.0 mg), sucrose (800 mg), and Water for Injection, USP. The pH is 6.0.

REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, is authorized for use under an EUA for the treatment of mild to moderate COVID-19 in adult and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Limitations of Authorized Use REGEN-COV is not authorized for treatment of mild to moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information such as variant susceptibility to this drug and regional variant frequency. - FDA's determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs. REGEN-COV (casirivimab and imdevimab) is not authorized for use in patients: - who are hospitalized due to COVID-19, OR - who require oxygen therapy due to COVID-19, OR - who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation [see Warnings and Precautions (5.2) ] . REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, is authorized for use under an EUA for the post-exposure prophylaxis of COVID-19 in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death, and are: not fully vaccinated Individuals are considered to be fully vaccinated 2 weeks after their second vaccine dose in a 2-dose series (such as the Pfizer or Moderna vaccines), or 2 weeks after a single-dose vaccine (such as Johnson & Johnson's Janssen vaccine). See this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html#vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications See this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html ) and - have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC) Close contact with an infected individual is defined as: being within 6 feet for a total of 15 minutes or more, providing care at home to someone who is sick, having direct physical contact with the person (hugging or kissing, for example), sharing eating or drinking utensils, or being exposed to respiratory droplets from an infected person (sneezing or coughing, for example). See this website for additional details: https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html or - who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons). Limitations of Authorized Use REGEN-COV is not authorized for post-exposure prophylaxis of COVID-19 in geographic regions where exposure is likely to have been to a non-susceptible SARS-CoV-2 variant, based on available information including variant susceptibility to this drug and regional variant frequency. - FDA's determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs. Post-exposure prophylaxis with REGEN-COV (casirivimab and imdevimab) is not a substitute for vaccination against COVID-19. REGEN-COV (casirivimab and imdevimab) is not authorized for pre-exposure prophylaxis for prevention of COVID-19.

The optimal dosing regimen for treatment of COVID-19 has not yet been established. The recommended dosing regimen may be updated as data from clinical trials become available. Patient Selection for Treatment and Post-Exposure Prophylaxis Treatment: This section provides essential information on the unapproved product, REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, for the treatment of adult and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death [see Limitations of Authorized Use (1.1) ] . Post-Exposure Prophylaxis: This section provides essential information on the unapproved product, REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied in individual vials to be administered together, in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) for the post-exposure prophylaxis of COVID-19 in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death, and are: not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications ) and - have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC) or - who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons) [see Limitations of Authorized Use (1.2) ] . The following medical conditions or other factors may place adults and pediatric patients (age 12-17 years and weighing at least 40 kg) at higher risk for progression to severe COVID-19: Older age (for example, age ≥65 years of age) Obesity or being overweight (for example, BMI >25 kg/m 2 , or if age 12-17, have BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm) Pregnancy Chronic kidney disease Diabetes Immunosuppressive disease or immunosuppressive treatment Cardiovascular disease (including congenital heart disease) or hypertension Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension) Sickle cell disease Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies) Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)) Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of REGEN-COV under the EUA is not limited to the medical conditions or factors listed above. For additional information on medical conditions and factors associated with increased risk for progression to severe COVID-19, see the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient. Treatment: The dosage in adult and pediatric patients (12 years of age and older weighing at least 40 kg) is 600 mg of casirivimab and 600 mg of imdevimab administered together as a single intravenous infusion or by subcutaneous injection. Casirivimab and imdevimab should be given together as soon as possible after a positive viral test for SARS-CoV-2 and within 10 days of symptom onset. Post-Exposure Prophylaxis: The dosage in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) is 600 mg of casirivimab and 600 mg of imdevimab administered by subcutaneous injection or together as a single intravenous infusion. Casirivimab and imdevimab should be given together as soon as possible following exposure to SARS-CoV-2. For individuals whom repeat dosing is determined to be appropriate for ongoing exposure to SARS-CoV-2 for longer than 4 weeks and who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination, the initial dose is 600 mg of casirivimab and 600 mg of imdevimab by subcutaneous injection or intravenous infusion followed by subsequent repeat dosing of 300 mg of casirivimab and 300 mg of imdevimab by subcutaneous injection or intravenous infusion once every 4 weeks for the duration of ongoing exposure. For Intravenous Infusion: Casirivimab and imdevimab solution co-formulated in a vial and in individual vials, including co-packaged carton and dose pack, must be diluted prior to intravenous administration. Administer casirivimab and imdevimab together as a single intravenous infusion via pump or gravity (see Table 1 , Table 2 , Table 3 and Table 4 ). Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete. For Subcutaneous Injection: Administer casirivimab and imdevimab using the co-formulated vial or using the individual vials by subcutaneous injection (see Table 5 and Table 6 ). Clinically monitor patients after injections and observe patients for at least 1hour. Pregnancy or Lactation No dosage adjustment is recommended in pregnant or lactating women [see Use in Specific Populations (11.1 , 11.2) ] . Pediatric Use No dosage adjustment is recommended in pediatric patients who weigh at least 40 kg and are older than 12 years of age. REGEN-COV (casirivimab and imdevimab) is not recommended for pediatric patients weighing less than 40 kg or those less than 12 years of age [see Use in Specific Populations (11.3) ] . Renal Impairment No dosage adjustment is recommended in patients with renal impairment [see Use in Specific Populations (11.5) ]. There are TWO different formulations of REGEN-COV: Casirivimab and imdevimab co-formulated solution containing two antibodies in a 1:1 ratio in a vial. Casirivimab and imdevimab available as individual antibody solutions in separate vials supplied as follows: Individual vials in individual cartons, or together in a single carton (also referred to as a co-packaged carton), or in a dose pack. The dose pack contains individual vials of casirivimab and imdevimab, configurations that may vary in vial size, strength and appearance and are available in dose pack configurations that include 2, 5, and 8 cartons [see Full EUA Prescribing Information, How Supplied/Storage and Handling (19) ]. For treatment, intravenous infusion is strongly recommended. Subcutaneous injection is an alternative route of administration when intravenous infusion is not feasible and would lead to delay in treatment. For post-exposure prophylaxis, either subcutaneous injection or intravenous infusion can be used. There are differences in the way the two formulations are prepared. Carefully follow the preparation procedures below. Casirivimab and imdevimab co-formulated solution in a vial and casirivimab or imdevimab as individual antibody solutions in separate 11.1 mL vials may be used to prepare more than one dose simultaneously as appropriate, either in intravenous bags or in syringes for subcutaneous injection. Discard any product remaining in the vial. Store unopened casirivimab and imdevimab vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Unopened vials may be stored in the original carton at room temperature [up to 25°C (77°F)] and must be used within 30 days. If not used in the 30 days, discard vials. Under the EUA, a single-dose vial may be used to prepare more than one dose. Preparation for Intravenous Infusion For treatment, the preferred route of administration for casirivimab and imdevimab is by intravenous infusion after dilution. Casirivimab and imdevimab solution for intravenous infusion should be prepared by a qualified healthcare professional using aseptic technique: Remove the casirivimab and imdevimab vials from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake the vials . Inspect casirivimab and imdevimab vials visually for particulate matter and discoloration prior to administration. Should either be observed, the vial must be discarded and replaced with a new vial. The solution for each vial should be clear to slightly opalescent, colorless to pale yellow. Obtain a prefilled intravenous infusion bag containing either 50 mL, 100 mL, 150 mL, or 250 mL of either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Withdraw the appropriate amount of casirivimab and imdevimab from each respective vial(s) and inject into a prefilled infusion bag containing either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, (see Table 1 and Table 2 ). If using one vial to prepare more than one infusion bag, then prepare all infusion bags at the same time. The product is preservative-free, therefore do not store unused solution in vial(s). Gently invert infusion bag by hand approximately 10 times to mix. Do not shake . This product is preservative-free and therefore, the diluted infusion solution should be administered immediately (see Table 3 and Table 4 ). If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution in the refrigerator between 2°C to 8°C (36°F to 46°F) for no more than 36 hours or at room temperature up to 25°C (77°F) for no more than 4 hours. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration. Table 1: Recommended Dilution Instructions for 600 mg of Casirivimab and 600 mg of Imdevimab for Intravenous Infusion Size of Prefilled 0.9% Sodium Chloride or 5% Dextrose Infusion Bag Preparing Using Co-Formulated Casirivimab and Imdevimab Vial Preparing Casirivimab and Imdevimab Using Individual Vials 600 mg of casirivimab and 600 mg of imdevimab are added to the same infusion bag and administered together as a single intravenous infusion. 50 mL Add 10 mL of co-formulated casirivimab and imdevimab (1 vial) into a prefilled 0.9% Sodium Chloride or 5% Dextrose infusion bag and administer as instructed below Add: 5 mL of casirivimab (may use 2 vials of 2.5 mL OR 1 vial of 11.1 mL) and 5 mL of imdevimab (may use 2 vials of 2.5 mL OR 1 vial of 11.1 mL) and inject into a prefilled 0.9% Sodium Chloride or 5% Dextrose infusion bag and administer as instructed below 100 mL 150 mL 250 mL Table 2: Recommended Dilution Instructions for 300 mg of Casirivimab and 300 mg of Imdevimab for Intravenous Infusion for Repeat Dosing Subsequent repeat dosing every 4 weeks after initial 600 mg casirivimab and 600 mg imdevimab dosing for the duration of ongoing exposure. Size of Prefilled 0.9% Sodium Chloride or 5% Dextrose Infusion Bag Preparing Using Co-Formulated Casirivimab and Imdevimab Vial Preparing Casirivimab and Imdevimab Using Individual Vials 300 mg of casirivimab and 300 mg of imdevimab are added to the same infusion bag and administered together as a single intravenous infusion. 50 mL Add 5 mL of co-formulated casirivimab and imdevimab into a prefilled 0.9% Sodium Chloride or 5% Dextrose infusion bag and administer as instructed below Add: 2.5 mL of casirivimab (may use 1 vial of 2.5 mL OR 1 vial of 11.1 mL) and 2.5 mL of imdevimab (may use 1 vial of 2.5 mL OR 1 vial of 11.1 mL) and inject into a prefilled 0.9% Sodium Chloride or 5% Dextrose infusion bag and administer as instructed below 100 mL 150 mL 250 mL Administration by Intravenous Infusion Casirivimab and imdevimab infusion solution should be administered by a qualified healthcare professional using aseptic technique. Gather the recommended materials for infusion: Polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set In-line or add-on 0.2 micron polyethersulfone (PES) filter Attach the infusion set to the intravenous bag. Prime the infusion set. Administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone (PES) filter (see Table 3 and Table 4 ). Due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage. The prepared infusion solution should not be administered simultaneously with any other medication. The compatibility of casirivimab and imdevimab injection with intravenous solutions and medications other than 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP is not known. After infusion is complete, flush the tubing with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to ensure delivery of the required dose. Discard unused product. Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete. Table 3: Recommended Administration Rate for 600 mg of Casirivimab and 600 mg of Imdevimab for Intravenous Infusion Size of Prefilled 0.9% Sodium Chloride or 5% Dextrose Infusion Bag used Maximum Infusion Rate Minimum Infusion Time 50 mL The minimum infusion time for patients administered casirivimab and imdevimab together using the 50 mL prefilled 0.9% Sodium Chloride or 5% Dextrose infusion bag must be at least 20 minutes to ensure safe use. 180 mL/hr 20 minutes 100 mL 310 mL/hr 21 minutes 150 mL 310 mL/hr 31 minutes 250 mL 310 mL/hr 50 minutes Table 4: Recommended Administration Rate for 300 mg of Casirivimab and 300 mg of Imdevimab for Intravenous Infusion for Repeat Dosing Subsequent repeat dosing every 4 weeks after initial 600 mg casirivimab and 600 mg imdevimab dosing for the duration of ongoing exposure. Size of Prefilled 0.9% Sodium Chloride or 5% Dextrose Infusion Bag used Maximum Infusion Rate Minimum Infusion Time 50 mL The minimum infusion time for patients administered casirivimab and imdevimab together using the 50 mL prefilled 0.9% Sodium Chloride or 5% Dextrose infusion bag must be at least 20 minutes to ensure safe use. 165 mL/hr 20 minutes 100 mL 310 mL/hr 20 minutes 150 mL 310 mL/hr 30 minutes 250 mL 310 mL/hr 49 minutes Preparation for Subcutaneous Injection Remove the casirivimab and imdevimab vial(s) from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake the vials. Inspect casirivimab and imdevimab vial(s) visually for particulate matter and discoloration prior to administration. Should either be observed, the vial must be discarded and replaced with a new vial. The solution for each vial should be clear to slightly opalescent, colorless to pale yellow. Casirivimab and imdevimab should be prepared using the appropriate number of syringes (see Table 5 and Table 6 ). Obtain 3 mL or 5 mL polypropylene Luer Lock syringes with luer connection and 21-gauge 1½ inch transfer needles. Withdraw the appropriate amount of solution into each syringe (see Table 5 and Table 6 ). Prepare all syringes at the same time. Replace the 21-gauge transfer needle with a 25-gauge or 27-gauge needle for subcutaneous injection. This product is preservative-free and therefore, the prepared syringes should be administered immediately. If immediate administration is not possible, store the prepared casirivimab and imdevimab syringes in the refrigerator between 2ºC to 8ºC (36ºF to 46ºF) for no more than 24 hours, or at room temperature up to 25ºC (77ºF) for no more than 8 hours. If refrigerated, allow the syringes to equilibrate to room temperature for approximately 20 minutes prior to administration. Table 5: Preparation of 600 mg of Casirivimab and 600 mg of Imdevimab for Subcutaneous Injections Prepare 600 mg of Casirivimab and 600 mg of Imdevimab Preparation of 4 Syringes Using Casirivimab and Imdevimab Co-formulated Vial Withdraw 2.5 mL solution per syringe into FOUR separate syringes. Using Casirivimab and Imdevimab Individual Vials Casirivimab: Withdraw 2.5 mL solution per syringe into TWO separate syringes. Imdevimab: Withdraw 2.5 mL solution per syringe into TWO separate syringes. For total of 4 syringes. Table 6: Preparation of 300 mg of Casirivimab and 300 mg of Imdevimab for Subcutaneous Injections for Repeat Dosing Subsequent repeat dosing every 4 weeks after initial 600 mg casirivimab and 600 mg imdevimab dosing for the duration of ongoing exposure. Prepare 300 mg of Casirivimab and 300 mg of Imdevimab Preparation of 2 Syringes Using Casirivimab and Imdevimab Co-formulated Vial Withdraw 2.5 mL solution per syringe into TWO separate syringes. Using Casirivimab and Imdevimab Individual Vials Casirivimab: Withdraw 2.5 mL solution into ONE syringe. Imdevimab: Withdraw 2.5 mL solution into ONE syringe. For total of 2 syringes. Administration for Subcutaneous Injection For the administration of 600 mg of casirivimab and 600 mg of imdevimab, gather 4 syringes (see Table 5 ) and prepare for subcutaneous injections. For the administration of 300 mg of casirivimab and 300 mg of imdevimab, gather 2 syringes (see Table 6 ) and prepare for subcutaneous injections. Administer the subcutaneous injections consecutively, each at a different injection site, into the thigh, back of the upper arm, or abdomen, except for 2 inches (5 cm) around the navel. The waistline should be avoided. When administering the subcutaneous injections, it is recommended that providers use different quadrants of the abdomen or upper thighs or back of the upper arms to space apart each 2.5 mL subcutaneous injection of casirivimab and imdevimab. DO NOT inject into skin that is tender, damaged, bruised, or scarred. Clinically monitor patients after injections and observe patients for at least 1 hour.

REGEN-COV (casirivimab and imdevimab) is available as: A single vial which contains two antibodies co-formulated in a 1:1 ratio of casirivimab and imdevimab. Co-formulated casirivimab and imdevimab is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution available as: Injection: 600 mg of casirivimab and 600 mg of imdevimab per 10 mL (60 mg/60 mg per mL) in a single-dose Under the EUA, a single-dose vial may be used to prepare more than one dose. vial Individual antibody solutions in separate single-dose vials, which may be supplied in separate cartons or together in a single carton (also referred to as a co-packaged carton), or as dose pack. Casirivimab is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution available as: Injection: 300 mg/2.5 mL (120 mg/mL) or 1,332 mg/11.1 mL (120 mg/mL) Imdevimab is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution available as: Injection: 300 mg/2.5 mL (120 mg/mL) or 1,332 mg/11.1 mL (120 mg/mL) Each REGEN-COV dose pack contains 1,200 mg of casirivimab [REGN10933] and 1,200 mg of imdevimab [REGN10987] [see How Supplied/Storage and Handling (19) ] . Casirivimab and imdevimab vial labels and carton labeling may instead be labeled REGN10933 and REGN10987, respectively.

REGEN-COV is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to REGEN-COV [see Warnings and Precautions (5.1) ] .

There are limited clinical data available for REGEN-COV (casirivimab and imdevimab). Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use. Serious hypersensitivity reactions, including anaphylaxis, have been reported with administration of REGEN-COV (casirivimab and imdevimab). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of REGEN-COV. These reactions may be severe or life threatening. Signs and symptoms of infusion related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, fatigue, and diaphoresis [see Overall Safety Summary (6.1) ] . If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under Emergency Use Authorization. Clinical worsening of COVID-19 after administration of REGEN-COV has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to REGEN-COV use or were due to progression of COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, REGEN-COV is not authorized for use in patients [see Limitations of Authorized Use (1.1) ] : who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19, OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.

Overall, approximately 16,000 subjects have been exposed to REGEN-COV (casirivimab and imdevimab) in clinical trials in hospitalized and non-hospitalized subjects. Approximately 13,500 subjects received intravenous infusions and 2,500 subjects received subcutaneous injections.

REGEN-COV consists of 2 monoclonal antibodies (mAbs), casirivimab and imdevimab, which are not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Risk Summary There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. REGEN-COV (casirivimab and imdevimab) 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 casirivimab and imdevimab. In a tissue cross-reactivity study with casirivimab and imdevimab using human fetal tissues, no binding of clinical concern was detected. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, casirivimab and imdevimab have the potential to be transferred from the mother to the developing fetus. It is unknown whether the potential transfer of casirivimab and imdevimab provides any treatment benefit or risk to the developing fetus. There are maternal and fetal risks associated with untreated COVID-19 in pregnancy (see Clinical Considerations ). 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. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. Risk Summary There are no available data on the presence of casirivimab and/or imdevimab 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 REGEN-COV (casirivimab and imdevimab) and any potential adverse effects on the breastfed child from REGEN-COV or from the underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. REGEN-COV is not authorized for use in pediatric patients under 12 years of age or weighing less than 40 kg. The safety and effectiveness of casirivimab and imdevimab are being assessed in pediatric and adolescent patients in an ongoing clinical trial. The recommended dosing regimen is expected to result in comparable serum exposures of casirivimab and imdevimab in patients 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 Trials COV-2067, COV-2069, and COV-2093. Of the 4,567 subjects with SARS-CoV-2 infection randomized in Trial COV-2067, 14% were 65 years or older, and 4% were 75 years of age or older. Of the 3,029 subjects randomized in Trial COV-2069, 9% were 65 years or older and 2% were 75 years of age or older. Of the 974 subjects randomized in Trial COV-2093, 13% were 65 years or older and 2% were 75 years of age or older. The difference in pharmacokinetics (PK) of casirivimab and imdevimab in geriatric patients compared to younger patients is unknown [see Clinical Trial Results and Supporting Data for EUA (18.1) ] . Casirivimab and imdevimab are not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of casirivimab and imdevimab. The effect of hepatic impairment on PK of casirivimab and imdevimab is unknown. The effect of other covariates (e.g., sex, race, body weight, disease severity) on PK of casirivimab and imdevimab is unknown.

How Supplied Co-formulated casirivimab and imdevimab injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution supplied in a vial. Refer to Table 12. Casirivimab injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution supplied in a vial. Refer to Table 13. Imdevimab injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution supplied in a vial. Refer to Table 13. REGEN-COV (casirivimab and imdevimab) injection is available as: 1. A single vial which contains two antibodies co-formulated in a 1:1 ratio of casirivimab and imdevimab ( Table 12). 2. Individual antibody solutions in separate vials, which may be supplied in separate cartons ( Table 13) or together in a single carton (also referred to as a co-packaged carton) ( Table 14) , or in a dose pack ( Table 15) . Table 12: Co-Formulated Casirivimab and Imdevimab Antibody Concentration Package Size NDC Number REGEN-COV (casirivimab and imdevimab) 600 mg/600 mg per 10 mL (60 mg/60 mg per mL) 1 vial per carton 61755-039-01 INDIVIDUAL CASIRIVIMAB AND IMDEVIMAB SOLUTIONS MUST BE ADMINISTERED TOGETHER. Table 13: Individual Package Size Antibody Concentration Package Size NDC Number Casirivimab REGN10933 1,332 mg/11.1 mL (120 mg/mL) 1 vial per carton 61755-024-01 300 mg/2.5 mL (120 mg/mL) 1 vial per carton 61755-026-01 Imdevimab REGN10987 1,332 mg/11.1 mL (120 mg/mL) 1 vial per carton 61755-025-01 300 mg/2.5 mL (120 mg/mL) 1 vial per carton 61755-027-01 Each co-packaged carton contains 1 vial of casirivimab and 1 vial of imdevimab. Refer to Table 14. Table 14: Casirivimab and Imdevimab Co-Packaged Carton Co-Packaged Carton Contents Co-Packaged Components Concentration Co-Packaged Carton NDC Number 2 Vials 1 vial of casirivimab (NDC 61755-024-00) 1,332 mg/11.1 mL (120 mg/mL) 61755-042-02 1 vial of imdevimab (NDC 61755-025-00) 1,332 mg/11.1 mL (120 mg/mL) 2 Vials 1 vial of casirivimab (NDC 61755-026-00) 300 mg/2.5 mL (120 mg/mL) 61755-045-02 1 vial of imdevimab (NDC 61755-027-00) 300 mg/2.5 mL (120 mg/mL) Each REGEN-COV dose pack contains sufficient number of vials of casirivimab [REGN10933] and imdevimab [REGN10987] to prepare up to two treatment doses (600 mg of casirivimab and 600 mg of imdevimab). Refer to Table 15. Table 15: Dose Pack Providing 1,200 mg Casirivimab and 1,200 mg Imdevimab REGEN-COV Dose Pack Size REGEN-COV Dose Pack Components Concentration REGEN-COV Dose Pack NDC Number 2 Cartons 1 vial of casirivimab REGN10933 (NDC 61755-024-01) 1,332 mg/11.1 mL (120 mg/mL) 61755-035-02 1 vial of imdevimab REGN10987 (NDC 61755-025-01) 1,332 mg/11.1 mL (120 mg/mL) 8 Cartons 4 vials of casirivimab REGN10933 (NDC 61755-026-01) 300 mg/2.5 mL (120 mg/mL) 61755-036-08 4 vials of imdevimab REGN10987 (NDC 61755-027-01) 300 mg/2.5 mL (120 mg/mL) 5 Cartons 1 vial of casirivimab REGN10933 (NDC 61755-024-01) 1,332 mg/11.1 mL (120 mg/mL) 61755-037-05 4 vials of imdevimab REGN10987 (NDC 61755-027-01) 300 mg/2.5 mL (120 mg/mL) 5 Cartons 4 vials of casirivimab REGN10933 (NDC 61755-026-01) 300 mg/2.5 mL (120 mg/mL) 61755-038-05 1 vial of imdevimab REGN10987 (NDC 61755-025-01) 1,332 mg/11.1 mL (120 mg/mL) Storage and Handling Casirivimab is preservative-free. Discard any unused portion. Imdevimab is preservative-free. Discard any unused portion. Store unopened casirivimab and imdevimab vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Unopened vials may be stored in the original carton at room temperature [up to 25°C (77°F)] and must be used within 30 days. If not used in the 30 days, discard vials. DO NOT FREEZE. DO NOT SHAKE. DO NOT EXPOSE TO DIRECT LIGHT. Solution in vial requires dilution prior to intravenous administration. The prepared infusion solution is intended to be used immediately. If immediate administration is not possible, store diluted casirivimab and imdevimab infusion solution in the refrigerator at 2°C to 8°C (36°F to 46°F) for no more than 36 hours or at room temperature up to 25°C (77°F) for no more than 4 hours. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration. The prepared syringes should be administered immediately. If immediate administration is not possible, store the prepared casirivimab and imdevimab syringes in the refrigerator between 2ºC to 8ºC (36ºF to 46ºF) for no more than 24 hours, or at room temperature up to 25ºC (77ºF) for no more than 8 hours. If refrigerated, allow the syringes to equilibrate to room temperature for approximately 20 minutes prior to administration.

Casirivimab (IgG1κ) and imdevimab (IgG1λ) are two recombinant human mAbs which are unmodified in the Fc regions. Casirivimab and imdevimab bind to non-overlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2 with dissociation constants K D = 45.8 pM and 46.7 pM, respectively. Casirivimab, imdevimab and casirivimab and imdevimab together blocked RBD binding to the human ACE2 receptor with IC 50 values of 56.4 pM, 165 pM and 81.8 pM, respectively and prevents viral attachment to host cells [ see Microbiology/Resistance Information (15) ]. Trial COV-2067 evaluated REGEN-COV (casirivimab and imdevimab) with doses of up to 6.66 times the recommended dose (600 mg of casirivimab and 600 mg of imdevimab; 1,200 mg of casirivimab and 1,200 mg of imdevimab; 4,000 mg of casirivimab and 4,000 mg of imdevimab) in ambulatory patients with COVID-19. A flat dose-response relationship for efficacy was identified for REGEN-COV at all doses, based on viral load and clinical outcomes. Similar reductions in viral load (log10 copies/mL) were observed in subjects for the (600 mg of casirivimab and 600 mg of imdevimab) intravenous and (600 mg of casirivimab and 600 mg of imdevimab) subcutaneous doses; however, only limited clinical outcome data are available for the subcutaneous route of administration for the treatment of symptomatic patients. Both casirivimab and imdevimab exhibited linear and dose-proportional pharmacokinetics (PK) between (600 mg of casirivimab and 600 mg of imdevimab) to (4,000 mg of casirivimab and 4,000 mg of imdevimab) doses of REGEN-COV (casirivimab and imdevimab) following intravenous administration of single dose. A summary of PK parameters after a single (600 mg of casirivimab and 600 mg of imdevimab) intravenous dose, for each antibody is provided in Table 7. Table 7: Summary of PK Parameters for Casirivimab and Imdevimab After a Single 600 mg of Casirivimab and 600 mg of Imdevimab Intravenous Dose of REGEN-COV in Study COV-2067 PK Parameter Mean (SD) Casirivimab Imdevimab C eoi (mg/L) concentration at end of 1-hour infusion 192 (80.9) 198 (84.8) C 28 (mg/L) observed concentration 28 days after dosing, i.e., on day 29, as defined in the protocol 46.2 (22.3) 38.5 (19.7) A summary of PK parameters after a single 600 mg of casirivimab and 600 mg of imdevimab subcutaneous dose is shown in Table 8. Table 8: Summary of PK Parameters for Casirivimab and Imdevimab After a Single 600 mg of Casirivimab and 600 mg of Imdevimab Subcutaneous Dose of REGEN-COV PK Parameter Mean (SD) , Mean (SD) concentration at 24 hours (C 24 ) of casirivimab and imdevimab in serum with 1200 SC dosing, 22.5 (11.0) mg/L and 25.0 (16.4) mg/L, respectively Casirivimab Imdevimab C max (mg/L) 55.6 (22.2) 52.7 (22.5) t max (day) Median (range) 8.00 (4.00, 87.0) 7.00 (4.00, 15.0) AUC 0-28 (mg∙day/L) 1060 (363) 950 (362) AUC inf (mg∙day/L) Value reported for subjects with %AUC inf extrapolated <20% 2580 (1349) 1990 (1141) C 28 (mg/L) Observed concentration 28 days after dosing, i.e., on day 29 30.7 (11.9) 24.8 (9.58) Half-life (day) 31.8 (8.35) 26.9 (6.80) For the repeat dose prophylaxis intravenous and subcutaneous regimens, population pharmacokinetic simulations predicted that trough concentrations in serum at steady-state after an initial 600 mg casirivimab and 600 mg imdevimab intravenous or subcutaneous dose followed by monthly (every 4 weeks) 300 mg casirivimab and 300 mg imdevimab intravenous or subcutaneous doses are similar to slightly higher than observed mean day 29 concentrations in serum for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose. Specific Populations The effect of different covariates (e.g., age, sex, race, body weight, disease severity, hepatic impairment) on the PK of casirivimab and imdevimab is unknown. Renal impairment is not expected to impact the PK of casirivimab and imdevimab, since mAbs with molecular weight >69 kDa are known not to undergo renal elimination. Similarly, dialysis is not expected to impact the PK of casirivimab and imdevimab. Drug-Drug Interactions Casirivimab and imdevimab are mAbs which are not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely [see Drug Interactions (10) ] .

Carcinogenicity, genotoxicity, and reproductive toxicology studies have not been conducted with casirivimab and imdevimab. In a toxicology study in cynomolgus monkeys, casirivimab and imdevimab had no adverse effects when administered intravenously or subcutaneously. Non-adverse liver findings (minor transient increases in AST and ALT) were observed. In tissue cross-reactivity studies with casirivimab and imdevimab using human adult and fetal tissues, no binding of clinical concern was detected.

701208 12345-00 Casirivimab Injection NDC 61755-026-00 Rx only 300 mg/2.5 mL (120 mg/mL) For Intravenous Infusion after Dilution For use under Emergency Use Authorization (EUA) MUST ADMINISTER WITH IMDEVIMAB Mfd by: Regeneron Pharmaceuticals, Inc. LOT/EXP PRINCIPAL DISPLAY PANEL - 300 mg/2.5 mL Vial Label - Casirivimab