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Aug.18.2021

Casirivimab; Imdevimab

Indications/Dosage

Labeled

    Individuals are deemed to be at high risk for progressing to severe COVID-19 if they meet at least 1 of the following criteria:

    • Elderly (65 years or older)
    • Obesity or overweight
      • Body mass index (BMI) greater than 25 kg/m2
      • If age 12 to 17 years, BMI greater than or equal to 85th percentile for age and gender based on CDC growth charts
    • Pregnancy
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or receiving immunosuppressive therapy
    • Cardiovascular disease (including congential heart disease) or hypertension
    • Chronic lung disease (e.g., chronic obstructive pulmonary disease, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorder (e.g., cerebral palsy) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes, severe congential anomalies)
    • Medical-related technological dependency (e.g., tracheostomy, gastrostomy, positive pressure ventilation not related to COVID-19)

    In addition, other medical conditions or factors (e.g., race, ethnicity) may also place individual patients at high risk, and authorization of casirivimab and imdevimab under the EUA is not limited to only those medical conditions or factors listed above. Health care providers are advised to consider the benefit-to-risk of an individual patient.[66127]

    Off-Label

    • coronavirus disease 2019 (COVID-19)
    • prevention of coronavirus disease 2019 (COVID-19)
    • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
    † Off-label indication

    INVESTIGATIONAL USE: For the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection† resulting in mild to moderate coronavirus disease 2019 (COVID-19)† in patients who are at high risk for progressing to severe COVID-19, including hospitalization or death

    NOTE: Casirivimab and imdevimab are not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[66127]

    NOTE: The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend anti-SARS-CoV-2 antibodies be considered for use in high risk persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. Additionally, although these antibodies are not authorized for use in patients hospitalized due to severe COVID-19, the NIH states that they may be available through expanded access programs for patients who have not developed an antibody response or who are not expected to mount an effective immune response to SARS-CoV-2 infection.[65314]

    Intravenous dosage

    Adults weighing 40 kg or more

    The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Administer 600 mg of casirivimab and 600 mg of imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127]

    Children and Adolescents 12 years and older weighing 40 kg or more

    The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Administer 600 mg of casirivimab and 600 mg of imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients with mild to moderate COVID-19. The NIH recommends the use of these antibodies be considered on a case-by-case basis in consultation with a pediatric infectious diseases specialist.[65314]

    Subcutaneous dosage

    Adults weighing 40 kg or more

    The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Give 600 mg of casirivimab and 600 mg of imdevimab via 4 consecutive subcutaneous injections at different injection sites. Administer the injections as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127]

    Children and Adolescents 12 years and older weighing 40 kg or more

    The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Give 600 mg of casirivimab and 600 mg of imdevimab via 4 consecutive subcutaneous injections at different injection sites. Administer the injections as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients with mild to moderate COVID-19. The NIH recommends the use of these antibodies be considered on a case-by-case basis in consultation with a pediatric infectious diseases specialist.[65314]

    INVESTIGATIONAL USE: For the post-exposure prevention of coronavirus disease 2019 (COVID-19)† in patients who are at high risk for progressing to severe COVID-19, including hospitalization or death

    NOTE: Post-exposure prophylaxis may be considered in high risk patients who are either not fully vaccinated (i.e., at least 2 weeks after completing the dosing series) OR not expected to mount an adequate immune response to the SARS-CoV-2 vaccination (e.g., immunocompromised condition, immunosuppressive medications) AND 1 of the following:

    • exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per the Centers for Disease Control and Prevention (CDC)
    • at high risk of exposure to individual(s) infected with SARS-CoV-2 because the infection(s) occurred within the same institutional setting (e.g., nursing homes, prisons)[66127] [65314]

    NOTE: Casirivimab and imdevimab are not authorized for pre-exposure prophylaxis, nor should they be used as a substitute for the COVID-19 vaccines.[66127] [65314]

    Intravenous dosage

    Adults weighing 40 kg or more

    600 mg casirivimab and 600 mg imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by a single intravenous infusion once every 4 weeks for the duration of ongoing exposure.[66127] The National Institutes of Health (NIH) recommends a single prophylactic dose of 600 mg casirivimab and 600 mg imdevimab be administered as soon as possible, and preferably within 7 days of exposure; however, unlike the FDA's Emergency Use Authorization, the NIH states there are insufficient data to recommend either for or against repeated dosing every 4 weeks for those who continue to have high risk exposures.[65314]

    Children and Adolescents 12 years and older weighing 40 kg or more

    600 mg casirivimab and 600 mg imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by a single intravenous infusion once every 4 weeks for the duration of ongoing exposure.[66127] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients. The NIH recommends the use of these antibodies be considered on a case-by-case basis.[65314]

    Subcutaneous dosage

    Adults weighing 40 kg or more

    600 mg casirivimab and 600 mg imdevimab via subcutaneous injections. Administer the injections as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by subcutaneous injections once every 4 weeks for the duration of ongoing exposure.[66127] The National Institutes of Health (NIH) recommends a single prophylactic dose of 600 mg casirivimab and 600 mg imdevimab be administered as soon as possible, and preferably within 7 days of exposure; however, unlike the FDA's Emergency Use Authorization, the NIH states there are insufficient data to recommend either for or against repeated dosing every 4 weeks for those who continue to have high risk exposures.[65314]

    Children and Adolescents 12 years and older weighing 40 kg or more

    600 mg casirivimab and 600 mg imdevimab via subcutaneous injections. Administer the injections as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by subcutaneous injections once every 4 weeks for the duration of ongoing exposure.[66127] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients. The NIH recommends the use of these antibodies be considered on a case-by-case basis.[65314]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.

      less than 40 kg: Use not authorized.

    • Geriatric

      40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.

      less than 40 kg: Use not authorized.

    • Adolescents

      40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.

      less than 40 kg: Use not authorized.

    • Children

      12 years and weighing 40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.

      12 years and weighing less than 40 kg: Use not authorized.

      1 to 11 years: Use not authorized.

    • Infants

      Use not authorized.

    • Neonates

      Use not authorized.

    Patients with Hepatic Impairment Dosing

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Patients with Renal Impairment Dosing

    No dosage adjustments are needed.

    † Off-label indication
    Revision Date: 08/18/2021, 04:06:14 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

    How Supplied

    Casirivimab Solution for injection

    Casirivimab 1332mg/11.1mL Solution for Injection (61755-0024) (Regeneron Pharmaceuticals Inc.) (off market)

    Casirivimab Solution for injection

    Casirivimab 300mg/2.5mL Solution for Injection (61755-0026) (Regeneron Pharmaceuticals Inc.) (off market)

    Casirivimab Solution for injection, Imdevimab Solution for injection

    REGEN-COV 1332mg/11.1mL Solution for Injection Dose Pack (61755-0035) (Regeneron Pharmaceuticals Inc.) null

    Casirivimab, Imdevimab Solution for injection

    REGEN-COV 600mg-600mg/10mL Solution for Injection (61755-0039) (Regeneron Pharmaceuticals Inc.) null

    Imdevimab Solution for injection

    Imdevimab 1332mg/11.1mL Solution for Injection (61755-0025) (Regeneron Pharmaceuticals Inc.) (off market)

    Imdevimab Solution for injection

    Imdevimab 300mg/2.5mL Solution for Injection (61755-0027) (Regeneron Pharmaceuticals Inc.) (off market)

    Description/Classification

    Description

    Casirivimab and imdevimab are investigational neutralizing human immunoglobulin G-1 (IgG1) monoclonal antibodies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They are not an FDA-approved treatment; however, they have been authorized for emergency use as a treatment for mild to moderate COVID-19 in patients (12 years and older weighing at least 40 kg) with positive SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death. They are also authorized for use as post-exposure prophylaxis of COVID-19 in persons (12 years and older weighing at least 40 kg) exposed to SARS-CoV-2 who are at high risk for progressing to severe COVID-19 and are not fully vaccinated or are not expected to mount an adequate immune response to the complete COVID-19 vaccination. They are NOT authorized for treatment of patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of these drugs in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes. Additionally, the combination is not authorized for pre-exposure prophylaxis, nor should it be used as a substitute for the COVID-19 vaccines.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend individuals who have recently been exposed to SARS-CoV-2 and have symptoms consistent with COVID-19 be evaluated for SARS-CoV-2 infection.

    • If test results are positive for SARS-CoV-2, the NIH recommends using anti-SARS-CoV-2 monoclonal antibodies (including casirivimab and imdevimab) to treat nonhospitalized adults with mild to moderate COVID-19 who are at high risk of clinical progression as defined by the Emergency Use Authorization (EUA) criteria. Anti-SARS-CoV-2 antibodies should also be considered for treatment of high risk adults with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. While these antibodies are not authorized for use in patients hospitalized due to severe COVID-19, they may be available through expanded access programs for patients who have not developed an antibody response or who are not expected to mount an effective immune response to SARS-CoV-2 infection. Treatment with anti-SARS-CoV-2 antibodies should be started as soon as possible after positive test results for SARS-CoV-2 and within 10 days of symptom onset.
    • If test results are negative for SARS-CoV-2, consider use of casirivimab and imdevimab as post-exposure prophylaxis in adults who would be at high risk of clinical progression if infected (as defined by the EUA) and who are not fully vaccinated or are fully vaccinated but not expected to mount an adequate immune response. The NIH recommends a single prophylactic dose of casirivimab and imdevimab be administered as soon as possible, and preferably within 7 days of exposure; however, unlike the FDA's EUA, the NIH states there are insufficient data to recommend either for or against repeated dosing every 4 weeks for those who continue to have high risk exposures.

    In situations where it is necessary to triage eligible patients (i.e., antibody shortages, logistical constraints), the NIH suggests prioritizing treatment dosing over post-exposure prophylaxis and prioritizing to unvaccinated/incompletely vaccinated high risk individuals or vaccinated individuals not expected to mount an adequate immune response over vaccinated individuals who are expected to have developed an adequate immune response. These considerations should NOT limit the use of anti-SARS-CoV-2 antibodies when there are no logistical constraints. For patients who receive anti-SARS-CoV-2 antibodies, defer administration of the COVID-19 vaccination for at least 90 days as a precaution to avoid interference with vaccine-induced immune responses. Conversely, the use and timing of treatment with anti-SARS-CoV-2 antibodies should not be affected by prior vaccinations in patients who develop COVID-19 after receiving the vaccine.[65314]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Antiviral Monoclonal Antibodies for SARS-CoV-2
    Revision Date: 09/03/2021, 03:10:58 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

     

    NOTE: Casirivimab and imdevimab are not FDA-approved medications; however, they have been authorized for emergency use as a treatment for mild to moderate COVID-19 in patients with positive SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death. They are also authorized for use as post-exposure prophylaxis of COVID-19 in persons exposed to SARS-CoV-2 who are at high risk for progressing to severe COVID-19 and are not fully vaccinated or are not expected to mount an adequate immune response to the complete COVID-19 vaccination. Under the Emergency Use Authorization (EUA), health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents and Caregivers" prior to the patient receiving treatment; such information includes the following:

    • The option to accept or refuse casirivimab and imdevimab
    • The significant known and potential risks and benefits of treatment, and the extent to which such potential risks and benefits are unknown
    • Available alternative treatments and the risk and benefits of those alternatives
    • The need to continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect, frequent handwashing) according to CDC guidelines

    NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to casirivimab and imdevimab therapy within 7 calendar days from the onset of the event.[66127]

    Route-Specific Administration

    Injectable Administration

    • Must be administered in a setting in which health care providers have immediate access to medications used to treat a severe infusion reaction and the ability to activate the emergency medical system, as necessary.
    • Available in 2 different formulations:
      • Single vial containing a co-formulated solution of the 2 antibodies in a 1:1 ratio.
        • 600 mg casirivimab and 600 mg imdevimab per 10 mL (60 mg/60 mg per mL).
      • Dose pack containing casirivimab and imdevimab in separate individual vials.
        • Casirivimab in 300 mg/2.5 mL (120 mg/mL) or 1,332 mg/11.1 mL (120 mg/mL) single-dose vials.
        • Imdevimab in 300 mg/2.5 mL (120 mg/mL) or 1,332 mg/11.1 mL (120 mg/mL) single-dose vials.
      • If using the co-formulated solution or the 1,332 mg/11.1 mL vials, multiple doses may be prepared simultaneously as appropriate. Discard any product remaining in the vial.
    • For treatment, intravenous infusion is the preferred route of administration and is strongly recommended; subcutaneous injections are an alternative route of administration to be given when use of the infusion is not feasible or would lead to delay in treatment.[65314] For post-exposure prophylaxis, either the intravenous infusion or the subcutaneous injections may be administered.
    • Visually inspect parenteral products for particulate matter and discoloration prior to drug administration. Casirivimab and imdevimab are clear to slightly opalescent, colorless to pale yellow solutions.[66127]

    Intravenous Administration

    Preparation and Dilution:

    • The infusion should be prepared and administered by a qualified health care professional using aseptic technique. The product does not contain a preservative.
    • Remove casirivimab and imdevimab vial(s) from the refrigerator and allow them to equilibrate to room temperature (approximately 20 minutes). DO NOT expose to direct heat or shake the vials.
    • Select a prefilled infusion bag containing either 50 mL, 100 mL, 150 mL, or 250 mL of 0.9% Sodium Chloride Injection. Choose 1 size.
    • Withdraw the appropriate amount of casirivimab and imdevimab from the vial(s) and inject into the same prefilled infusion bag. Discard any remaining product in the vials.
      • For the 600 mg casirivimab and 600 mg imdevimab dose:
        • If using the co-formulated solution: Add 10 mL of solution to the infusion bag.
        • If using the dose pack individual vials: Add 5 mL of casirivimab and 5 mL of imdevimab from each of the respective vials to the infusion bag. For both casirivimab and imdevimab, each dose requires either one 11.1 mL vial or two 2.5 mL vials.
      • For the 300 mg casirivimab and 300 mg imdevimab dose:
        • If using the co-formulated solution: Add 5 mL of solution to the infusion bag.
        • If using the dose pack individual vials: Add 2.5 mL of casirivimab and 2.5 mL of imdevimab from each of the respective vials to the infusion bag. For both casirivimab and imdevimab, each dose requires either one 11.1 mL vial or one 2.5 mL vial.
    • Gently invert the infusion bag by hand approximately 10 times to mix. DO NOT shake.
    • Storage: Use immediately after dilution. If immediate administration is not possible, the diluted solution may be stored at room temperature up to 25 degrees C (77 degrees F) for no more than 4 hours or under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for no more than 36 hours (including infusion time). If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes before administration.[66127]

     

    Intravenous Infusion:

    • Obtain a polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set and an in-line or add-on 0.2 micron polyethersulfone (PES) filter.
    • Attach the infusion set to the IV infusion bag.
    • Prime the infusion set.
    • Administer the entire infusion solution in the bag via pump or gravity through an IV line containing a sterile, in-line or add-on 0.2-micron PES filter. Due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage. The minimum infusion duration is dependent on the dose and size of the infusion bag used:
      • For the 600 mg casirivimab and 600 mg imdevimab dose:
        • If using 50 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 180 mL/hour; Minimum infusion time of 20 minutes
        • If using 100 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 310 mL/hour; Minimum infusion time of 21 minutes
        • If using 150 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 310 mL/hour; Minimum infusion time of 31 minutes
        • If using 250 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 310 mL/hour; Minimum infusion time of 50 minutes
      • For the 300 mg casirivimab and 300 mg imdevimab dose:
        • If using 50 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 165 mL/hour; Minimum infusion time of 20 minutes
        • If using 100 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 310 mL/hour; Minimum infusion time of 20 minutes
        • If using 150 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 310 mL/hour; Minimum infusion time of 30 minutes
        • If using 250 mL prefilled 0.9% Sodium Chloride bag: Maximum infusion rate of 310 mL/hour; Minimum infusion time of 49 minutes
    • The prepared infusion solution should not be administered simultaneously with other medications. The compatibility of casirivimab and imdevimab with solutions or medications other than 0.9% Sodium Chloride Injection is not known.
    • Once the infusion is complete, flush the IV line with 0.9% Sodium Chloride Injection to ensure delivery of the required dose. Discard any remaining product.
    • Clinically monitor patients during the infusion and for at least 1 hour after the infusion is complete.[66127]

    Subcutaneous Administration

    Preparation:

    • The injections should be prepared and administered by a qualified health care professional using aseptic technique. The product does not contain a preservative.
    • Remove casirivimab and imdevimab vial(s) from the refrigerator and allow them to equilibrate to room temperature (approximately 20 minutes). DO NOT expose to direct heat or shake the vials.
    • Obtain the appropriate number of 3 mL or 5 mL polypropylene Luer Lock syringes with luer connection and 21-gauge 1.5 inch transfer needles.
    • Using the syringes and transfer needles, prepare the dose as follows (prepare all syringes at the same time):
      • For the 600 mg casirivimab and 600 mg imdevimab dose:
        • If using the co-formulated solution: Withdraw 2.5 mL of the 1:1 solution per syringe into 4 separate syringes. Total dose 10 mL.
        • If using the dose pack individual vials: Withdraw 2.5 mL of casirivimab solution per syringe into 2 separate syringes, then withdrawal 2.5 mL of imdevimab solution per syringe into the other 2 syringes. Total dose 10 mL.
      • For the 300 mg casirivimab and 300 mg imdevimab dose:
        • If using the co-formulated solution: Withdraw 2.5 mL of the 1:1 solution per syringe into 2 separate syringes. Total dose 5 mL.
        • If using the dose pack individual vials: Withdraw 2.5 mL of casirivimab solution into 1 syringe, then withdrawal 2.5 mL of imdevimab solution into another syringe. Total dose 5 mL.
    • Replace the 21-gauge transfer needles with 25- or 27-gauge needles for subcutaneous injection.
    • Storage: Use immediately. If immediate administration is not possible, the prepared syringes may be stored under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) or at room temperature up to 25 degrees C (77 degrees F) for no more than 4 hours. If refrigerated, allow the syringes to equilibrate to room temperature for approximately 20 minutes before administration.[66127]

     

    Subcutaneous Injection:

    • Gather the prepared syringes (i.e., 4 syringes for the 600 mg/600 mg dose or 2 syringes for the 300 mg/300 mg dose)
    • Administer the subcutaneous injections consecutively at different injections sites into the thigh, back of the upper arm, or abdomen (except for 2 inches around the navel). Avoid the waistline
    • It is advised to use different quadrants of the abdomen, upper thighs, or back of the upper arms in order to space out the injections.
    • Do not inject into skin that is tender, damaged, bruised, or scarred.
    • Clinically monitor patients for at least 1 hour after the injections.[66127]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Casirivimab; Imdevimab

    pH Range
    pH is 6.
      Revision Date: 08/02/2021, 05:56:59 PMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

      Adverse Reactions

      Mild

      • ecchymosis
      • fever
      • flushing
      • injection site reaction
      • nausea
      • pruritus
      • rash
      • urticaria
      • vomiting

      Moderate

      • dyspnea
      • erythema
      • infusion-related reactions

      Severe

      • anaphylactoid reactions

      The safety of casirivimab and imdevimab has been evaluated in a phase 1/2/3 trial involving non-hospitalized patients with mild to moderate COVID-19, a phase 3 post-exposure prophylaxis trial, and a phase 1 safety and pharmacokinetics trial. In the treatment trial, patients were randomized to receive either a placebo (n = 1,843) or single infusions of casirivimab and imdevimab at the following doses: 600 mg/600 mg (n = 827); 1,200 mg/1,200 mg (n = 1,849); 4,000 mg/4,000 mg (n = 1,012). Note, neither the 1,200 mg/1,200 mg nor the 4,000 mg/4,000 mg dose is not authorized the EUA. Of the patients who received casirivimab and imdevimab at the authorized dose or a higher dose, 0.2% experienced infusion-related reactions that were Severity Grade 2 or higher. Permanent discontinuation of the infusion due to an infusion-related reaction (e.g., urticaria, pruritus, flushing, fever, dyspnea, chest tightness, nausea, vomiting, rash) occurred in 3 patients in the 4,000 mg/4,000 mg group and 1 in the 1,200 mg/1,200 mg group. All events resolved upon treatment discontinuation.[66127]

      Anaphylactic or anaphylactoid reactions have been reported in patients treated with casirivimab and imdevimab during the clinical program. These adverse events began within 1 hour of the completed infusion, and at least 1 case required treatment with epinephrine which resolved the event. In clinical trials evaluating the safety of administering casirivimab and imdevimab via subcutaneous injections, hypersensitivity reactions were reported in up to 1% of drug recipients. In all cases, the reactions were Grade 1 or 2 in severity, and there were no reports of anaphylaxis.[66127]

      The safety of administering casirivimab and imdevimab via subcutaneous injections was evaluated in a randomized, double-blind, placebo-controlled trial involving healthy adults. In these trial, subjects received repeated subcutaneous doses of either 600 mg casirivimab and 600 mg imdevimab (n = 729) or placebo (n = 240) every 4 weeks for 24 weeks. An evaluation of the data found 12% of subjects receiving casirivimab and imdevimab and 4% of subjects in the placebo group developed an injection site reaction after a single dose. With repeated dosing, the incidence of injection site reactions increased to 35% in the casirivimab and imdevimab group and 16% in the placebo group (all Grade 1 or 2). Of note, the 600 mg/600 mg dose used in the study was higher than the authorized dose for repeated subcutaneous injections (after the initial dose) of 300 mg casirivimab and 300 mg imdevimab. In another trial, subcutaneous doses of casirivimab and imdevimab were administered to subjects as post-exposure prophylaxis. In the post-exposure prophylaxis trial, SARS-CoV-2 negative subjects at baseline (cohort A) were administered either 600 mg casirivimab and 600 mg imdevimab as a single subcutaneous dose (n = 1,311) or placebo (n = 1,306). Injection site reactions (all Grade 1 or 2) were reported in 4% of subjects who received casirivimab and imdevimab and 2% who received the placebo. Occurring in at least 1% of drug recipients, the most common injection site reactions were erythema and pruritus. In cohort B of the post-exposure trial, 155 subjects who were SARS-CoV-2 positive at baseline were administered 600 mg casirivimab and 600 mg imdevimab subcutaneously, while 156 subjects were administered a placebo. In this cohort, injection site reactions (all Grade 1 or 2) were reported in 4% of subjects who received casirivimab and imdevimab and 1% who received the placebo. The most common injection site reactions in this cohort were ecchymosis and erythema (both occurring in at least 1% of drug recipients).[66127]

      Revision Date: 08/02/2021, 05:37:13 PM

      References

      66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • breast-feeding
      • infusion-related reactions
      • pregnancy

      Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worsening clinical outcomes when administered to hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation. Therefore, the drug is not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition.[66127]

      Infusion-related reactions have been observed during and for up to 24 hours after treatment with casirivimab and imdevimab; these reactions may be severe or life-threatening. Signs and symptoms of these reactions include fever, chills, nausea, headache, bronchospasms, dyspnea, reduced oxygen saturation, fatigue, arrhythmia exacerbation (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, hypotension, hypertension, angioedema, throat irritation, rash, urticaria, pruritus, myalgia, dizziness, syncope, and diaphoresis. If an infusion-related reaction develops, consider slowing or stopping the infusion and administer appropriate medications and supportive care. Similarly, serious hypersensitivity reactions, including anaphylaxis, have been observed during and for more than 24 hours after treatment with casirivimab and imdevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue treatment and initiate appropriate medications and supportive care.[66127]

      There are insufficient data regarding the use of casirivimab and imdevimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. 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 if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, casirivimab and imdevimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that the drug not be withheld from a pregnant woman at high risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.[65314]

      There are no data regarding the presence of casirivimab or imdevimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[66127]

      Revision Date: 06/11/2021, 01:11:57 PM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

      Mechanism of Action

      Casirivimab and imdevimab are recombinant human immunoglobulin G-1 (IgG1) monoclonal antibodies used in combination as an antiviral medication to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antibodies bind to non-overlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2, which prevents the virus from interacting with the human ACE2 receptor. In Jurkat target cells expressing SARS-CoV-2 spike proteins, the combination of casirivimab plus imdevimab elicited antibody-dependent cell-mediated cytotoxicity (ADCC) with human natural killer (NK) effector cells and antibody-dependent cellular phagocytosis (ADCP) with human macrophages. However, the combination did not mediate complement-dependent cytotoxicity in cell-based assays. The estimated 50% effective concentration (EC50) of casirivimab plus imdevimab in neutralizing SARS-CoV-2 in Vero cells is 0.005 mcg/mL.[66127][66130]

       

      There is a potential for treatment failure due to the development of viral variants that are resistant to the combination of casirivimab and imdevimab. Health care providers are advised to consider the prevalence of SARS-CoV-2 variants in their area when considering treatment options. In cell culture studies, spike protein amino acid substitutions in variants showing reduced susceptibility to casirivimab alone include K417E (182-fold), K417N (7-fold), K417R (61-fold), Y453F (more than 438-fold), L455F (80-fold), E484K (25-fold), F486V (more than 438-fold), and Q493K (more than 438-fold). Variants showing reduced susceptibility to imdevimab alone include substitutions K444N (more than 755-fold), K444Q (more than 548-fold), K444T (more than 1,033-fold), and V445A (548-fold). Casirivimab and imdevimab together show reduced susceptibility to variants with substitutions K444T (6-fold) and V445A (5-fold). In neutralization assays using VSV VLP pseudotyped with spike protein variants identified in circulating SARS-CoV-2, variants with reduced susceptibility to casirivimab alone included those with substitutions E406D (51-fold), V445T (107-fold), E484Q (19-fold), G485D (5-fold), G476S (5-fold), F486L (61-fold), F486S (more than 715-fold), Q493E (446-fold), Q493R (70-fold), and S494P (5-fold). Variants with reduced susceptibility to imdevimab alone included those with substitutions P337L (5-fold), N439K (463-fold), N439V (4-fold), N440K (28-fold), K444L (153-fold), K444M (1,577-fold), G446V (135-fold), N450D (9-fold), Q493R (5-fold), Q498H (17-fold), and P499S (206-fold). The G476D substitution has a 4-fold impact on casirivimab and imdevimab together. Neutralization data for SARS-CoV-2 variant substitutions identified through global surveillance have found no change in susceptibility (i.e., less than 2-fold reduction) to casirivimab and imdevimab together. The variants and key substitutions are as follows:

      • United Kingdom B.1.1.7 variant (Alpha): All spike protein substitutions found in this variant, including key variant N501Y
      • South Africa B.1.351 variant (Beta): All spike protein substitutions found in this variant, including key variants K417N, E484K, and N501Y
      • Brazil P.1 variant (Gamma): All spike protein substitutions found in this variant, including K417T, E484K, N501Y
      • California B.1.427/B.1.429 variant (Epsilon): L452R
      • New York B.1.526 variant (Iota): E484K
        • NOTE: Not all New York B.1.526 isolates harbored the E484K substitution
      • India B.1.617.1/B.1.617.3 variant (Kappa/no designation): L452R + E484Q
      • India B.1.617.2 variant (Delta): L452R + T478K

      It is unknown how these data correlate with clinical outcomes.[66127]

      Revision Date: 08/02/2021, 05:17:10 PM

      References

      66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download66130 - Hansen J, Baum A, Pascal KE, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 2020;369:1010-1014.

      Pharmacokinetics

      Casirivimab and imdevimab are administered together via intravenous infusion or subcutaneous injection. Data regarding the pharmacokinetics of casirivimab and imdevimab are limited; however, the pharmacokinetic profiles are expected to be consistent with the profile of other IgG1 monoclonal antibodies. Casirivimab and imdevimab are not metabolized by cytochrome P450 enzymes, nor are they renally excreted.[66127]

       

      Affected cytochrome P450 isoenzymes: none

      Route-Specific Pharmacokinetics

      Intravenous Route

      Following intravenous administration, casirivimab and imdevimab exhibit linear and dose-proportional pharmacokinetics between doses of 600 mg/600 mg and 4,000 mg/4,000 mg. Immediately after a single 600 mg/600 mg intravenous dose, the mean plasma concentrations for casirivimab and imdevimab were 192 mg/L and 198 mg/L, respectively. The mean concentrations for casirivimab and imdevimab on Day 29 (i.e., 28 days after dosing) were 46.2 mg/L and 38.5 mg/L, respectively. For the repeated dose prophylaxis regimens, population pharmacokinetic simulations predict that serum trough concentrations at steady-state after the initial 600 mg casirivimab and 600 mg imdevimab dose followed by every 4 week doses of 300 mg casirivimab and 300 mg imdevimab are similar to or slightly higher than observed mean Day 29 concentrations for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose.[66127]

      Subcutaneous Route

      Following a single subcutaneous dose of 600 mg casirivimab and 600 mg imdevimab, the mean maximum plasma concentrations (Cmax) of 55.6 mg/L and 52.7 mg/L, respectively, were achieved in 8 days (range: 4 to 87 days) for casirivimab and 7 days (range: 4 to 15 days) for imdevimab. Systemic exposures (AUC0-28) were 1,060 mg x day/L for casirivimab and 950 mg x day/L for imdevimab. The observed mean plasma concentrations on Day 29 (i.e., 28 days after dosing) were 30.7 mg/L for casirivimab and 24.8 mg/L for imdevimab. The half-lives of casirivimab and imdevimab after subcutaneous injections were 31.8 days and 26.9 days, respectively. For the repeat dose prophylaxis regimens, population pharmacokinetic simulations predict that serum trough concentrations at steady-state after the initial 600 mg casirivimab and 600 mg imdevimab dose followed by every 4 week doses of 300 mg casirivimab and 300 mg imdevimab are similar to or slightly higher than observed mean Day 29 concentrations for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose.[66127]

      Special Populations

      Renal Impairment

      Monoclonal antibodies with a molecular weight greater than 69 kDa are known not to undergo renal elimination; therefore, renal impairment and dialysis are not expected to impact the pharmacokinetics of casirivimab (145.23 kDa) or imdevimab (144.14 kDa).[66127]

      Pediatrics

      The recommended dosing regimen is expected to result in comparable serum exposures of casirivimab and imdevimab in pediatric patients (12 years and older weighing at least 40 kg) as observed in adults.[66127]

      Revision Date: 08/02/2021, 05:55:57 PM

      References

      66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

      Pregnancy/Breast-feeding

      pregnancy

      There are insufficient data regarding the use of casirivimab and imdevimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. 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 if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, casirivimab and imdevimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that the drug not be withheld from a pregnant woman at high risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.[65314]

      breast-feeding

      There are no data regarding the presence of casirivimab or imdevimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[66127]

      Revision Date: 06/11/2021, 01:11:57 PM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download

      Interactions

      There are no drug interactions associated with Casirivimab; Imdevimab products.
      Revision Date: 01/09/2021, 02:34:00 AM

      References

      Monitoring Parameters

      • laboratory monitoring not necessary

      US Drug Names

      • REGEN-COV
      ;