Casirivimab and Imdevimab (Monograph)

Brand name: REGEN-COV
Drug class: Monoclonal Antibodies
- SARS-CoV-2-specific Monoclonal Antibody

Medically reviewed by Drugs.com on Jan 22, 2024. Written by ASHP.

Introduction

Antiviral; recombinant human IgG₁ neutralizing monoclonal antibodies specific for SARS-CoV-2 virus; used in a combination regimen.

Uses for Casirivimab and Imdevimab

Coronavirus Disease 2019 (COVID-19)

Being investigated for and has been used for treatment of COVID-19^{† [off-label]} caused by SARS-CoV-2. Also being investigated for and has been used for prevention of COVID-19^{† [off-label]}.

One of several SARS-CoV-2-specific monoclonal antibody regimens being evaluated for treatment and prevention of COVID-19.

Although efficacy and safety not definitely established, casirivimab and imdevimab is available under an FDA emergency use authorization (EUA) for treatment of mild to moderate COVID-19 and for postexposure prophylaxis of COVID-19 in certain individuals at high risk for progressing to severe COVID-19, including hospitalization or death.

On November 21, 2020, FDA issued an EUA that permits use of casirivimab and imdevimab for treatment of mild to moderate COVID-19^{† [off-label]} in adults and pediatric patients ≥12 years of age weighing ≥40 kg with positive results of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19. The EUA was reissued on February 25, 2021 to incorporate new conditions, including a requirement that the manufacturer establish a process for monitoring genomic databases for emergence of global viral variants of SARS-CoV-2 and, if requested by FDA, assess activity of casirivimab and imdevimab against any global SARS-CoV-2 variants of interest. On June 3, 2021, the EUA was reissued to authorize a change in casirivimab and imdevimab dosage, a new formulation (casirivimab and imdevimab co-formulated in a 1:1 ratio), and an additional route of administration (sub-Q injection) as an alternative when IV infusion is not feasible and would lead to delay in treatment. On July 30, 2021, FDA reissued the EUA for casirivimab and imdevimab to authorize use for postexposure prophylaxis of COVID-19^{† [off-label]} in certain adults and pediatric patients ≥12 years of age weighing ≥40 kg at risk for progressing to severe COVID-19, including hospitalization or death.

FDA issued the EUA for casirivimab and imdevimab for treatment of COVID-19 after concluding that emergency use of the drugs met criteria for issuance of an EUA for the following reasons: SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness; based on the totality of scientific evidence available to FDA, it is reasonable to believe that casirivimab and imdevimab administered together may be effective in treating mild to moderate COVID-19 in adults and pediatric patients ≥12 years of age weighing ≥40 kg who have positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing to severe COVID-19, including hospitalization or death, and, when used under the conditions described in the EUA, known and potential benefits of the drugs outweigh known and potential risks; and there are no adequate, approved, and available alternatives to emergency use of casirivimab and imdevimab for treatment of COVID-19 in such patients.

FDA expanded the EUA for casirivimab and imdevimab to permit use for postexposure prophylaxis of COVID-19 in susceptible individuals at high risk for progression to severe COVID-19, including hospitalization or death, following exposure to SARS-CoV-2, including those at high risk of ongoing exposure, after concluding that it is reasonable to believe that casirivimab and imdevimab may be effective for postexposure prophylaxis in such individuals and, when used under the conditions described in the EUA, known and potential benefits outweigh known and potential risks and there are no adequate, approved, and available alternatives to emergency use of casirivimab and imdevimab for postexposure prophylaxis of COVID-19.

When determining appropriate use of casirivimab and imdevimab under the EUA for treatment or postexposure prophylaxis of COVID-19, FDA states consider the following medical conditions and other factors that may place adults and pediatric patients ≥12 years of age at high risk for progression to severe COVID-19: older age (e.g., ≥65 years of age); obesity or being overweight (e.g., body mass index [BMI] >25 kg/m² or, in those 12–17 years of age, BMI ≥85th percentile for their age and gender based on CDC growth charts); pregnancy; chronic kidney disease; diabetes mellitus; immunosuppressive disease or immunosuppressive therapy; cardiovascular disease (including congenital heart disease) or hypertension; chronic lung disease (e.g., COPD, moderate to severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension); sickle cell disease; neurodevelopmental disorders (e.g., cerebral palsy) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes, severe congenital anomalies); or medical-related technological dependence (e.g., tracheostomy, gastrostomy, positive-pressure ventilation not related to COVID-19).

FDA also states use of casirivimab and imdevimab under the EUA for the treatment or postexposure prophylaxis of COVID-19 is not limited only to the medical conditions and factors listed above; other medical conditions and factors (e.g., race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19. Consider the benefits versus risks for the individual patient when making decisions regarding use of FDA-authorized SARS-CoV-2-specific monoclonal antibodies, including casirivimab and imdevimab. Additional information on medical conditions and factors associated with increased risk for progression to severe COVID-19 is available at [Web].

Casirivimab and imdevimab is not authorized under the EUA for treatment of COVID-19 in patients who are hospitalized due to COVID-19, require oxygen therapy due to COVID-19, or are on chronic oxygen therapy due to an underlying non-COVID-19-related comorbidity and require an increase in baseline oxygen flow rate due to COVID-19. SARS-CoV-2-specific monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized COVID-19 patients requiring high-flow oxygen or mechanical ventilation.

If a patient is hospitalized for reasons other than COVID-19 (e.g., an elective orthopedic procedure) and reports mild to moderate symptoms of COVID-19, confirmed with positive results of a direct SARS-CoV-2 viral test, FDA states that treatment with casirivimab and imdevimab may be appropriate if the patient is also at high risk for progression to severe COVID-19, including COVID-19-related hospitalization or death, and terms and conditions of the EUA are met.

Casirivimab and imdevimab is authorized under the EUA for postexposure prophylaxis of COVID-19 (PEP) in adults and pediatric patients ≥12 years of age weighing ≥40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death, and are exposed to an individual infected with SARS-CoV-2 under the following circumstances: the exposed individual is not considered fully vaccinated against COVID-19 (fully vaccinated defined as ≥2 weeks have elapsed since completion of a 2-dose vaccination series of an mRNA vaccine [Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine] or ≥2 weeks have elapsed since vaccination with a single dose of the Janssen COVID-19 vaccine) or the exposed individual is not expected to mount an adequate immune response to a complete COVID-19 vaccination series (e.g., because of immunocompromising condition or immunosuppressive therapy) and the exposure to an individual infected with SARS-CoV-2 was consistent with CDC's definition of close contact (i.e., within 6 feet of the infected individual for a total of ≥15 minutes, providing care at home to someone who is sick, having direct physical contact with an infected individual [e.g., hugging or kissing], sharing eating or drinking utensils, or being exposed to respiratory droplets from an infected individual [e.g., sneezing or coughing]) or there is high risk of ongoing exposure to an individual infected with SARS-CoV-2 because of SARS-CoV-2 infection in other individuals in the same institutional setting (e.g., nursing homes, prisons).

Postexposure prophylaxis with casirivimab and imdevimab is not a substitute for vaccination against COVID-19.

Casirivimab and imdevimab is not authorized for preexposure prophylaxis (PrEP) for prevention of COVID-19.

The EUA requires that casirivimab and imdevimab be administered by a health care provider in an appropriate setting using the dosages recommended in the EUA. (See Dosage and Administration.)

The EUA for casirivimab and imdevimab authorizes that distribution of the drugs will be controlled by the US government for use consistent with the terms and conditions of the EUA. (See Restricted Distribution under Preparations.)

To mitigate risks of these unapproved drugs, the EUA includes certain mandatory requirements (including providing information to the patient or parent/caregiver and ensuring that all medication errors and serious adverse events potentially attributable to the drugs are reported to FDA). (See EUA Requirements for Patient Monitoring and Mandatory FDA MedWatch Reporting under Cautions.)

Consult the casirivimab and imdevimab EUA letter of authorization ([Web]), EUA fact sheet for health care providers ([Web]), and EUA fact sheet for patients, parents, and caregivers ([Web]) for additional information.

Based on data available to date, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel recommends the use of SARS-CoV-2-specific monoclonal antibody therapy for the treatment of mild to moderate COVID-19 in outpatients at high risk of clinical progression as defined by the EUA criteria. Prior to mid-December 2021, bamlanivimab plus etesevimab, casirivimab plus imdevimab, and sotrovimab were the only therapies recommended by the Panel for outpatients with mild to moderate COVID-19 who are at high risk of progression to severe disease. Current recommendations for treating outpatients take into account the high prevalence of the B.1.1.529 (Omicron) variant of concern (VOC). The Omicron VOC is predicted to have markedly reduced susceptibility to bamlanivimab plus etesevimab and casirivimab plus imdevimab. The Panel favors the use of ritonavir-boosted nirmatrelvir in most high-risk outpatients with mild to moderate COVID-19. If ritonavir-boosted nirmatrelvir is unavailable or cannot be used because of drug interactions, the Panel recommends using sotrovimab in patients who live in areas with a high prevalence of the Omicron VOC. If sotrovimab is unavailable, the Panel recommends using a 3-day course of remdesivir. Molnupiravir should only be administered when the ritonavir-boosted nirmatrelvir, sotrovimab, and remdesivir are either not available or cannot be used.

In outpatients (ambulatory patients) with mild to moderate COVID-19 at high risk of progression to severe COVID-19, IDSA suggests use of SARS-CoV-2-specific monoclonal antibody therapy rather than no SARS-CoV-2-specific monoclonal antibody therapy, and recommends selection of the most appropriate SARS-CoV-2-specific monoclonal antibody regimen based on in vitro susceptibility data available for SARS-CoV-2 variants circulating locally.

Casirivimab and Imdevimab Dosage and Administration

General

• Circulating SARS-CoV-2 viral variants may be associated with reduced susceptibility to casirivimab and imdevimab (see Actions and Spectrum); consider prevalence of SARS-COV-2 variants in the local area, if available, when choosing treatment options. Information on SARS-CoV-2 viral variants circulating in the US collected through CDC's national genomic surveillance program is available at [Web] and may help guide treatment decisions.

• Must be administered in an appropriate setting in which health care providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS) as necessary.

• Must clinically monitor patient during administration of casirivimab and imdevimab and observe patient for at least 1 hour after IV infusion or sub-Q injection of the drugs is completed. (See Sensitivity and Infusion-related Reactions under Cautions.)

• Advise patients who receive casirivimab and imdevimab for treatment or postexposure prophylaxis of COVID-19 to continue to self-isolate and use infection control measures (e.g., wear mask, isolate, socially distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, wash hands frequently) according to CDC guidelines.

• Information for clinicians and infusion sites of care administering casirivimab and imdevimab to outpatients under the EUA, including recommendations for planning and implementation and considerations involving resources and equipment, may be available from the manufacturer or US Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR).

Administration

Administer casirivimab and imdevimab together by IV infusion or sub-Q injection.

For treatment of COVID-19: IV infusion preferred and strongly recommended; may administer by sub-Q injection if IV infusion not feasible and would lead to delay in treatment.

For postexposure prophylaxis of COVID-19: May administer by sub-Q injection or IV infusion.

Dosage and Administration Precautions

Manufacturer alerted health care providers about risk of medication errors because of availability of different preparations of casirivimab and imdevimab and variations in packaging and labeling.

Available as a solution containing a 1:1 ratio of the drugs (co-formulated casirivimab and imdevimab) in single-dose vials. For IV infusion, must dilute prior to IV infusion; for sub-Q injection, use undiluted.

Casirivimab and imdevimab also each available as solutions packaged individually in separate vials and cartons. For IV infusion, must be combined and administered together after dilution; for sub-Q injection, use undiluted and administer at separate injection sites.

Although some cartons and vials of casirivimab and some cartons and vials of imdevimab may be labeled “solution for intravenous administration” or “for intravenous infusion after dilution” without mention of the sub-Q route, any of the available vials of the drugs may used to prepare doses for IV infusion or sub-Q injection.

Some of the individual cartons and vials of casirivimab or imdevimab may be labeled REGN10933 or REGN10987, respectively.

Casirivimab and imdevimab may each be supplied as two different vial sizes (i.e., vials containing 1332 mg/11.1 mL or vials containing 300 mg/2.5 mL). Follow instructions for preparing the casirivimab and imdevimab solution for IV infusion or sub-Q injection (e.g., number of vials) to ensure correct dose.

Vials of casirivimab and vials of imdevimab may be shipped in “dose packs” consisting of a plastic bag containing a sufficient number of cartons and vials of the drugs to prepare 2 doses each providing 600 mg of casirivimab and 600 mg of imdevimab or 4 doses each providing 300 mg of casirivimab and 300 mg of imdevimab. There are 4 different dose pack presentations depending on vial sizes contained in the pack (see Preparations). Cartons and vials in the dose pack may vary in appearance and the cartons may have different lot numbers and expiration dates (the dose pack expiration date reflects the earliest expiration date of cartons in the pack). Dose pack bags are labeled REGEN-COV (casirivimab [REGN10933] with imdevimab [REGN10987]) and have functional barcodes and NDCs that were assigned based on the specific combination of cartons and vial sizes contained in the pack.

Individual cartons of casirivimab and individual cartons of imdevimab also remain in distribution; these cartons are not labeled with functional barcodes and NDCs.

Consider multiple strategies to mitigate risk of a possible medication error when preparing and administering casirivimab and imdevimab.

Information regarding the variations in individual carton and vial labeling (including images) available at [Web]. Direct questions and concerns about casirivimab and imdevimab packaging or use to the manufacturer at 844-734-6643 or [Web].

IV Infusion

Do not administer simultaneously through same IV infusion line with other drugs.

Use a polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set and a 0.2-µm polyethersulfone (PES) inline or add-on filter when administering the combined casirivimab and imdevimab solution.

After IV infusion is completed, flush infusion line with 0.9% sodium chloride or 5% dextrose injection to ensure delivery of entire dose.

Monitor patient during and for at least 1 hour after IV infusion completed.

Casirivimab and imdevimab contain no preservatives; discard any unused solution remaining in vial(s) and discard any diluted solution of the drugs not used within 4 hours after dilution.

For solution and drug compatibility information, see Compatibility under Stability.

Casirivimab and Imdevimab (Co-formulated)

Must dilute in 0.9% sodium chloride or 5% dextrose injection prior to IV infusion.

Remove single-dose vial of co-formulated casirivimab and imdevimab solution containing 600 mg of each drug per 10 mL (60 mg of each drug per mL) from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes.

Co-formulated solution should appear as a clear to slightly opalescent and colorless to pale yellow solution; discard if solution contains particulates or is discolored.

To prepare FDA-authorized dosages for IV infusion, withdraw appropriate volume of the co-formulated solution from the vial to provide the appropriate dose and dilute in a 50-, 100-, 150-, or 250-mL prefilled IV infusion bag containing 0.9% sodium chloride or 5% dextrose. (See Table 1.) Gently invert IV bag by hand approximately 10 times; do not shake.

Used for treatment or postexposure prophylaxis.

Used for postexposure prophylaxis if subsequent doses after the initial dose of 600 mg of casirivimab and 600 mg of imdevimab are appropriate because of high risk of ongoing exposure.

Administer immediately after dilution. If immediate administration not possible, may store diluted solution for up to 4 hours at room temperature (up to 25°C) or for up to 36 hours in a refrigerator (2–8°C). If diluted solution was refrigerated, allow it to equilibrate to room temperature for approximately 30 minutes prior to administration.

Casirivimab and Imdevimab (Supplied in Separate Vials)

Casirivimab and imdevimab each supplied as solutions in separate vials must be diluted together in 0.9% sodium chloride or 5% dextrose injection prior to IV infusion.

Remove appropriate number of vials of casirivimab solution and appropriate number of vials of imdevimab solution from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes. For each drug, depending on the dosage and vial size, this may be 1 or 2 vials containing 300 mg/2.5 mL (120 mg/mL) or 1 vial containing 1332 mg/11.1 mL (120 mg/mL). If using vials of casirivimab and imdevimab supplied in a dose pack, contents of the dose pack are sufficient to prepare 2 doses each providing 600 mg of casirivimab and 600 mg of imdevimab or 4 doses each providing 300 mg of casirivimab and 300 mg of imdevimab.

Casirivimab and imdevimab solutions should each appear as clear to slightly opalescent and colorless to pale yellow solutions; discard if solution contains particulates or is discolored.

To prepare the combined dilution, dilute the drugs in a 50-, 100-, 150-, or 250-mL prefilled IV infusion bag containing 0.9% sodium chloride or 5% dextrose. Using a separate syringe for each drug, withdraw the appropriate volume of casirivimab solution and appropriate volume of imdevimab solution from their respective vial(s) and transfer into the IV bag containing 0.9% sodium chloride or 5% dextrose. (See Table 2.) Gently invert IV bag by hand approximately 10 times; do not shake.

Used for treatment or postexposure prophylaxis.

Used for postexposure prophylaxis if subsequent doses after the initial dose of 600 mg of casirivimab and 600 mg of imdevimab are appropriate because of high risk of ongoing exposure.

Administer combined casirivimab and imdevimab solution immediately after dilution. If immediate administration not possible, may store combined diluted solution for up to 4 hours at room temperature (up to 25°C) or for up to 36 hours in a refrigerator (2–8°C), including infusion time. If combined diluted solution was refrigerated, allow it to equilibrate to room temperature for approximately 30 minutes prior to administration.

Rate of Administration

Administer by IV infusion via pump or gravity. Maximum IV infusion rate and minimum infusion time depend on the dose being administered and size of the IV infusion bag. (See Table 3 and Table 4.)

Used for treatment or postexposure prophylaxis.

If a 50-mL IV infusion bag prefilled with 0.9% sodium chloride or 5% dextrose is used, the minimum infusion time must be at least 20 minutes to ensure safe use.

Used for postexposure prophylaxis if subsequent doses after the initial dose of 600 mg of casirivimab and 600 mg of imdevimab are appropriate because of high risk of ongoing exposure.

If a 50-mL infusion bag prefilled with 0.9% sodium chloride or 5% dextrose is used, the minimum infusion time must be at least 20 minutes to ensure safe use.

Sub-Q Injection

For sub-Q injection, FDA-authorized dose of 600 mg of each drug is divided into 4 portions (total of 4 separate syringes) and FDA-authorized dose of 300 mg of each drug is divided into 2 portions (total of 2 separate syringes) and the portions of the total dose are administered consecutively into 4 or 2 separate injection sites, respectively.

Possible sub-Q injection sites include thigh, back of upper arm, or abdomen (except for 2 inches [5 cm] around navel). Avoid the waistline; do not inject into skin that is tender, damaged, bruised, or scarred. Manufacturer recommends using different quadrants of abdomen or upper thighs or back of upper arms so that the 4 sub-Q injections are spaced apart.

Monitor patient for at least 1 hour after sub-Q injections are completed.

Casirivimab and imdevimab contain no preservatives; discard any unused solution remaining in vial(s).

Casirivimab and Imdevimab (Co-formulated)

Remove single-dose vial of co-formulated casirivimab and imdevimab solution containing 600 mg of each drug per 10 mL (60 mg of each drug per mL) from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes.

Co-formulated casirivimab and imdevimab solution should appear as a clear to slightly opalescent and colorless to pale yellow solution; discard if solution contains particulates or is discolored.

To prepare FDA-authorized dosage of 600 mg of casirivimab and 600 mg of imdevimab for sub-Q injection, use four 3- or 5-mL polypropylene Luer Lock syringes (with luer connection) and four 21-gauge 1.5-inch transfer needles. Using the 4 syringes and 4 transfer needles, withdraw 2.5 mL of casirivimab and imdevimab solution from the 10-mL single-dose vial into each syringe; then replace each transfer needle with a 25- or 27-gauge needle for sub-Q injection. Prepare all 4 syringes at the same time.

To prepare FDA-authorized dosage of 300 mg of casirivimab and 300 mg of imdevimab for sub-Q injection, use two 3- or 5-mL polypropylene Luer Lock syringes (with luer connection) and two 21-gauge 1.5-inch transfer needles. Using the 2 syringes and 2 transfer needles, withdraw 2.5 mL of undiluted casirivimab and imdevimab solution from the 10-mL single-dose vial into each syringe; then replace each transfer needle with a 25- or 27-gauge needle for sub-Q injection. Prepare both syringes at the same time.

Administer total dose immediately after preparation. If immediate administration not possible, may store prefilled syringes for up to 24 hours in a refrigerator (2–8°C) or up to 8 hours at room temperature (up to 25°C).

Casirivimab and Imdevimab (Supplied in Separate Vials)

Under the EUA, single-dose vials of casirivimab or imdevimab may be used to prepare more than one dose. If one vial is used to prepare more than one infusion bag, prepare all infusion bags at the same time.

Remove appropriate number of vials of casirivimab solution and appropriate number of vials of imdevimab solution from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes. For each drug, depending on the dosage and vial size, this may be 1 or 2 vials containing 300 mg/2.5 mL (120 mg/mL) or 1 vial containing 1332 mg/11.1 mL (120 mg/mL). If using vials of casirivimab and imdevimab supplied in a dose pack, contents of the dose pack are sufficient to prepare 2 doses each providing 600 mg of casirivimab and 600 mg of imdevimab or 4 doses each providing 300 mg of casirivimab and 300 mg of imdevimab.

Casirivimab and imdevimab solutions should each appear as clear to slightly opalescent and colorless to pale yellow solutions; discard vials if solution contains particulates or is discolored.

To prepare FDA-authorized dosage of 600 mg of casirivimab and 600 mg of imdevimab for sub-Q injection, use four 3- or 5-mL polypropylene Luer Lock syringes (with luer connection) and four 21-gauge 1.5-inch transfer needles. Using 2 of the syringes and 2 of the transfer needles, withdraw 2.5 mL of casirivimab solution from the vial(s) into each of the 2 syringes; using the remaining 2 syringes and 2 transfer needles, withdraw 2.5 mL of imdevimab solution from the vial(s) into each of the 2 syringes. Then, replace transfer needles with 25- or 27-gauge needles for sub-Q injection. All 4 prefilled syringes (2 each containing 300 mg of casirivimab and 2 each containing 300 mg of imdevimab) are required for the total dose and should be prepared at the same time.

To prepare the FDA-authorized dosage of 300 mg of casirivimab and 300 mg of imdevimab for sub-Q injection, use two 3- or 5-mL polypropylene Luer Lock syringes (with luer connection) and two 21-gauge 1.5-inch transfer needles. Using one of the syringes and one of the transfer needles, withdraw 2.5 mL of undiluted casirivimab solution from the vial into the syringe; using the remaining syringe and transfer needle, withdraw 2.5 mL of undiluted imdevimab solution from the vial into the other syringe. Then, replace each transfer needle with a 25- or 27-gauge needle for sub-Q injection. Both prefilled syringes (one containing 300 mg of casirivimab and one containing 300 mg of imdevimab) are required for the total dose and should be prepared at the same time.

Administer total dose immediately after preparation. If immediate administration not possible, may store prefilled syringes for up to 4 hours in a refrigerator (2–8°C) or at room temperature (up to 25°C).

Dosage

Optimal dosage regimen of casirivimab and imdevimab administered together for treatment of COVID-19^{† [off-label]} not established. Dosage regimen recommended in the EUA may be updated as data from clinical trials become available.

Pediatric Patients

Coronavirus Disease 2019† (COVID-19)

Treatment of Mild to Moderate COVID-19†

IV

FDA EUA that permits use for treatment of mild to moderate disease (see Coronavirus Disease 2019 [COVID-19] under Uses) states that pediatric patients ≥12 years of age weighing ≥40 kg who are outpatients at high risk for progressing to severe COVID-19, including hospitalization or death, should receive 600 mg of casirivimab and 600 mg of imdevimab administered together as a single IV infusion.

Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset.

Sub-Q

FDA EUA that permits use for treatment of mild to moderate disease (see Coronavirus Disease 2019 [COVID-19] under Uses) states that pediatric patients ≥12 years of age weighing ≥40 kg who are outpatients at high risk for progressing to severe COVID-19, including hospitalization or death, may receive 600 mg of casirivimab and 600 mg of imdevimab by sub-Q injection (total dose divided into 4 portions and administered consecutively at 4 different injection sites). Sub-Q injection used as an alternative if IV infusion not feasible and would lead to delay in treatment. (See Administration under Dosage and Administration.)

Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset.

Prevention of COVID-19†

IV

FDA EUA that permits use for postexposure prophylaxis in those at high risk for progressing to severe COVID-19, including hospitalization or death, following exposure to an individual with SARS-CoV-2 infection under the circumstances specified in the EUA (see Coronavirus Disease 2019 [COVID-19] under Uses) states that pediatric patients ≥12 years of age weighing ≥40 kg should receive a single dose of 600 mg of casirivimab and 600 mg of imdevimab administered together as a single IV infusion.

Administer as soon as possible following exposure to SARS-CoV-2.

If additional doses are appropriate after the initial dose because of high risk of ongoing exposure to SARS-CoV-2 (lasting >4 weeks) in an individual not expected to mount an adequate immune response to a complete COVID-19 vaccination series, FDA EUA states that pediatric patients ≥12 years of age weighing ≥40 kg may receive a dose of 300 mg of casirivimab and 300 mg of imdevimab administered together by IV infusion once every 4 weeks for the duration of ongoing exposure.

Sub-Q

FDA EUA that permits use for postexposure prophylaxis in those at high risk for progressing to severe COVID-19, including hospitalization or death, following exposure to an individual with SARS-CoV-2 infection under the circumstances specified in the EUA (see Coronavirus Disease 2019 [COVID-19] under Uses) states that pediatric patients ≥12 years of age weighing ≥40 kg should receive a single dose of 600 mg of casirivimab and 600 mg of imdevimab administered together by sub-Q injection (total dose divided into 4 portions and administered consecutively at 4 different injection sites). (See Administration under Dosage and Administration.)

Administer as soon as possible following exposure to SARS-CoV-2.

If additional doses are appropriate after the initial dose because of high risk of ongoing exposure to SARS-CoV-2 (lasting >4 weeks) in an individual not expected to mount an adequate immune response to a complete COVID-19 vaccination series, FDA EUA states that pediatric patients ≥12 years of age weighing ≥40 kg may receive a dose of 300 mg of casirivimab and 300 mg of imdevimab administered together by sub-Q injection (total dose divided into 2 portions and administered consecutively at 2 different injection sites) once every 4 weeks for the duration of ongoing exposure.

Adults

Coronavirus Disease 2019† (COVID-19)

Treatment of Mild to Moderate COVID-19†

IV

FDA EUA that permits use for treatment of mild to moderate disease (see Coronavirus Disease 2019 [COVID-19] under Uses) states that adults who are outpatients at high risk for progressing to severe COVID-19, including hospitalization or death, should receive 600 mg of casirivimab and 600 mg of imdevimab administered together as a single IV infusion.

Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset.

Sub-Q

FDA EUA that permits use for treatment of mild to moderate disease (see Coronavirus Disease 2019 [COVID-19] under Uses) states that adults who are outpatients at high risk for progressing to severe COVID-19, including hospitalization or death, may receive 600 mg of casirivimab and 600 mg of imdevimab by sub-Q injection (total dose divided into 4 portions and administered consecutively at 4 different injection sites). Sub-Q injection used as an alternative if IV infusion not feasible and would lead to delay in treatment. (See Administration under Dosage and Administration.)

Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset.

Prevention of COVID-19†

IV

FDA EUA that permits use for postexposure prophylaxis in those at high risk for progressing to severe COVID-19, including hospitalization or death, following exposure to an individual with SARS-CoV-2 infection under the circumstances specified in the EUA (see Coronavirus Disease 2019 [COVID-19] under Uses) states that adults should receive a single dose of 600 mg of casirivimab and 600 mg of imdevimab administered together as a single IV infusion.

Administer as soon as possible following exposure to SARS-CoV-2.

If additional doses are appropriate after the initial dose because of high risk of ongoing exposure to SARS-CoV-2 (lasting >4 weeks) in an individual not expected to mount an adequate immune response to a complete COVID-19 vaccination series, FDA EUA states that adults may receive a dose of 300 mg of casirivimab and 300 mg of imdevimab administered together by IV infusion once every 4 weeks for the duration of ongoing exposure.

Sub-Q

FDA EUA that permits use for postexposure prophylaxis in those at high risk for progressing to severe COVID-19, including hospitalization or death, following exposure to an individual with SARS-CoV-2 infection under the circumstances specified in the EUA (see Coronavirus Disease 2019 [COVID-19] under Uses) states that adults should receive a single dose of 600 mg of casirivimab and 600 mg of imdevimab administered together by sub-Q injection (total dose divided into 4 portions and administered consecutively at 4 different injection sites). (See Administration under Dosage and Administration.)

Administer as soon as possible following exposure to SARS-CoV-2.

If additional doses are appropriate after the initial dose because of high risk of ongoing exposure to SARS-CoV-2 (lasting >4 weeks) in an individual not expected to mount an adequate immune response to a complete COVID-19 vaccination series, FDA EUA states that adults may receive a dose of 300 mg of casirivimab and 300 mg of imdevimab administered together by sub-Q injection (total dose divided into 2 portions and administered consecutively at 2 different injection sites) once every 4 weeks for the duration of ongoing exposure.

Prescribing Limits

Pediatric Patients

Coronavirus Disease 2019† (COVID-19)

IV or Sub-Q

Single dose for treatment.

Adults

Coronavirus Disease 2019† (COVID-19)

IV or Sub-Q

Single dose for treatment.

Special Populations

Hepatic Impairment

Effect of hepatic impairment unknown.

Renal Impairment

Dosage adjustment not needed.

Cautions for Casirivimab and Imdevimab

Contraindications

• Previous hypersensitivity reaction, including anaphylaxis, to casirivimab and imdevimab. (See Sensitivity and Infusion-related Reactions under Cautions.)

Warnings/Precautions

Sensitivity and Infusion-related Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported.

Anaphylactic reactions reported rarely in clinical trials; reactions began within 1 hour after completion of the IV infusion and resolved; at least one patient required treatment with epinephrine. There also have been post-authorization reports of hypersensitivity reactions occurring >24 hours after IV infusion of casirivimab and imdevimab.

Infusion-related reactions reported during and up to 24 hours after IV infusion; such reactions may be severe or life-threatening. Signs and symptoms of infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrhythmias (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, 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.

If signs and symptoms of anaphylaxis or other clinically important hypersensitivity reaction occur, immediately discontinue casirivimab and imdevimab IV infusion and initiate appropriate medications and/or supportive care.

If an infusion-related reaction occurs, slow or stop casirivimab and imdevimab IV infusion and initiate appropriate medications and/or supportive care.

Clinical Worsening after Casirivimab and Imdevimab Administration

Clinical worsening of COVID-19, including signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmias (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status, reported following administration of casirivimab and imdevimab; hospitalization required in some cases. It is not known if these events were related to the drug or occurred because of progression of COVID-19.

Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19

Not authorized for use under the EUA in patients who are hospitalized due to COVID-19, require oxygen therapy due to COVID-19, or are on chronic oxygen therapy due to an underlying non-COVID-19-related comorbidity and require an increase in baseline oxygen flow rate due to COVID-19.

SARS-CoV-2-specific monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized COVID-19 patients requiring high-flow oxygen or mechanical ventilation.

EUA Requirements for Patient Monitoring and Mandatory FDA MedWatch Reporting

Safety and efficacy not established. FDA issued an EUA that permits use of casirivimab and imdevimab for treatment of mild to moderate COVID-19^† or postexposure prophylaxis of COVID-19^† in certain adults and pediatric patients using the dosages recommended in the EUA. (See Coronavirus Disease 2019 [COVID-19] under Uses.)

Only limited data available to date regarding adverse effects associated with use of casirivimab and imdevimab. Serious and unexpected adverse events may occur that have not been previously reported with the drugs.

Completion of FDA MedWatch forms to report all medication errors and all serious adverse events potentially related to casirivimab and imdevimab is mandatory. Consult fact sheet for health care providers that is provided with the drugs and available at FDA website for requirements and instructions regarding reporting of adverse reactions and medication errors.

Specific Populations

Pregnancy

Data insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Estimated background risk of major birth defects and miscarriage related to COVID-19 unknown; however, disease-associated maternal and/or embryofetal 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.

Use during pregnancy only if potential benefit outweighs potential risk for the woman and fetus. If used in pregnant women, dosage adjustment not recommended.

NIH panel states do not withhold SARS-CoV-2-specific monoclonal antibody therapy, including casirivimab and imdevimab, from a pregnant woman who has a condition that poses a high risk of progression to severe COVID-19 if clinician thinks potential benefit of the drugs outweighs potential risk.

Nonclinical reproductive toxicity studies not performed. In a tissue cross-reactivity study with casirivimab and imdevimab using human fetal tissues, no binding of clinical concern detected. Human IgG₁ antibodies are known to cross the placenta; therefore, casirivimab and imdevimab have potential to be transferred from the pregnant woman to the developing fetus. Not known whether such potential placental transfer provides any treatment benefit or risk to the developing fetus.

Lactation

Not known whether casirivimab and imdevimab distribute into human or animal milk, have effects on breast-fed infant, or affect milk production. Maternal IgG is known to be present in human milk.

Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for casirivimab and imdevimab and any potential adverse effects on the breast-fed child from the drugs or from the underlying maternal condition. If used in lactating women, dosage adjustment not recommended. Women with COVID-19 who are breast-feeding should follow clinical guidelines to avoid exposing the infant to the virus.

Pediatric Use

The FDA EUA permits use for treatment of mild to moderate COVID-19^† or postexposure prophylaxis of COVID-19^† in certain pediatric patients ≥12 years of age weighing ≥40 kg (see Coronavirus Disease 2019 [COVID-19] under Uses).

Not authorized for use in pediatric patients <12 years of age or weighing <40 kg.

Safety and efficacy being evaluated in pediatric and adolescent patients in an ongoing clinical trial.

The EUA-recommended dosage is expected to result in serum exposures of the drugs in patients ≥12 years of age weighing ≥40 kg that are comparable to those observed in adults since adults with similar body weight were included in clinical trials evaluating IV infusion of casirivimab and imdevimab in outpatients with mild to moderate COVID-19 (NCT04425629; COV-2067) or sub-Q injection for postexposure prophylaxis of COVID-19 (NCT04452318; COV-2069) and also were included in a clinical trial evaluating the safety and pharmacokinetics of sub-Q injection of casirivimab and imdevimab in healthy adults (COV-2093).

Geriatric Use

Data from an ongoing trial evaluating casirivimab and imdevimab for treatment of mild to moderate COVID-19 in outpatients (COV-2067) indicated that 14% of the 4567 randomized patients were ≥65 years of age and 4% were ≥75 years of age.

In a trial evaluating sub-Q injection of casirivimab and imdevimab for postexposure prophylaxis of COVID-19 (COV-2069), 9% of the 3029 randomized individuals were ≥65 years of age and 2% were ≥75 years of age.

In a clinical trial evaluating safety and pharmacokinetics of sub-Q injection of casirivimab and imdevimab in healthy adults (COV-2093), 13% of the 974 randomized adults were ≥65 years of age and 2% were ≥75 years of age.

Difference in pharmacokinetics of casirivimab and imdevimab in geriatric patients compared with younger patients unknown.

Hepatic Impairment

Effect of hepatic impairment on pharmacokinetics of casirivimab and imdevimab unknown.

Renal Impairment

Not expected to affect casirivimab and imdevimab exposures; drugs not eliminated by renal excretion.

Common Adverse Effects

IV infusion: Data from a trial evaluating safety and efficacy of a single dose for treatment of mild to moderate COVID-19 in outpatients (COV-2067) indicate infusion-related reactions (adverse event assessed by the investigator to be causally related) with severity grade 2 or greater observed in 0.2% of patients who received casirivimab and imdevimab at FDA-authorized dosage or higher.

Sub-Q injection: Data from a trial evaluating safety and efficacy of a single dose for postexposure prophylaxis of COVID-19 in household contacts of individuals with SARS-CoV-2 (COV-2069) indicate that injection site reactions (all grade 1 or 2) occurred in 4% of those who received casirivimab and imdevimab and 2% of those who received placebo; most common injection site reactions were erythema and pruritus. In a trial evaluating safety and pharmacokinetics in healthy adults (COV-2090), injection site reactions reported in 12 or 4% of those who received a single sub-Q dose of casirivimab or placebo, respectively; other safety findings in the healthy adults were similar to safety data reported following IV infusion in the clinical trial in outpatients. Following repeated sub-Q doses given once every 4 weeks for up to 24 weeks in the healthy adults, injection site reactions (all grade 1 or 2) reported in 35 or 16% of those in the casirivimab and imdevimab group or placebo group, respectively.

Drug Interactions

Not metabolized by CYP isoenzymes and not renally excreted; interactions unlikely if used concomitantly with drugs that are substrates, inducers, or inhibitors of CYP isoenzymes or with drugs that are renally excreted.

Specific Drugs

Casirivimab and Imdevimab Pharmacokinetics

Absorption

Following single IV infusion of casirivimab and imdevimab (doses ranging from 600 mg of casirivimab and 600 mg of imdevimab to 4 g of casirivimab and 4 g of imdevimab), both drugs exhibit linear and dose-proportional pharmacokinetics.

Following single dose of 600 mg of casirivimab and 600 mg of imdevimab administered together by IV infusion over 1 hour, mean plasma concentrations of the drugs were 192 and 198 mg/L, respectively, at end of the infusion and 46.2 and 38.5 mg/L, respectively, on day 29.

Following single dose of 600 mg of casirivimab and 600 mg of imdevimab administered by sub-Q injection, mean peak plasma concentrations of the drugs were 55.6 and 52.7 mg/L, respectively, and were attained in a median of 8 or 7 days, respectively; on day 29, mean concentrations were 30.7 and 24.8 mg/L, respectively.

Population pharmacokinetic simulations evaluating repeated doses of casirivimab and imdevimab predict that trough serum concentrations at steady state after an initial dose of 600 mg of casirivimab and 600 mg of imdevimab given by IV infusion or sub-Q injection followed by doses of 300 mg of casirivimab and 300 mg of imdevimab given monthly (once every 4 weeks) by IV infusion or sub-Q injection are similar to or slightly higher than serum concentrations observed at a mean of 29 days following a single sub-Q dose of 600 mg of casirivimab and 600 mg of imdevimab.

At all doses evaluated, flat dose-response relationship for efficacy identified based on viral load and clinical outcomes in a clinical trial evaluating casirivimab and imdevimab administered together at doses up to 6.66 times higher than current FDA-authorized dosage (600 mg of casirivimab and 600 mg of imdevimab) for treatment of mild to moderate COVID-19 in outpatients (COV-2067). Although only limited clinical outcome data available regarding sub-Q injection of casirivimab and imdevimab for the treatment of COVID-19 in symptomatic patients, similar reductions in viral load (log₁₀ copies/mL) reported when FDA-authorized dosage administered by IV infusion or sub-Q injection.

Distribution

Not known whether casirivimab and imdevimab distribute into human or animal milk.

Elimination

Metabolism

Casirivimab and imdevimab not metabolized by CYP isoenzymes.

Elimination Route

Casirivimab and imdevimab not eliminated by renal excretion.

Dialysis not expected to affect pharmacokinetics of either drug.

Half-life

Sub-Q: Following single dose of 600 mg of casirivimab and 600 mg of imdevimab, half-lives of the drugs reported to be 31.8 and 26.9 days, respectively.

Special Populations

Renal impairment: Not expected to affect casirivimab and imdevimab exposures since monoclonal antibodies with molecular mass >69 kDa do not undergo renal elimination.

Effects of hepatic impairment, sex, race, body weight, or disease severity on pharmacokinetics of the drugs unknown.

Stability

Storage

Parenteral

Solution, for IV Infusion or Sub-Q Injection

Single-dose vials of co-formulated solution containing 1:1 ratio of the drugs: Refrigerate (2–8°C); store in original carton to protect from light. Do not freeze, shake, or expose to direct heat.

Vials containing casirivimab solution and vials containing imdevimab solution (supplied in individual cartons or in dose packs containing cartons of each drug): Refrigerate (2–8°C); store in original cartons or dose pack to protect from light. Do not freeze, shake, or expose to direct heat. Unopened vials may also be stored in original carton at room temperature (up to 25ºC) for up to 30 days; if not used in 30 days, discard vials.

Diluted solutions for IV infusion containing casirivimab and imdevimab prepared using co-formulated solution or by combining casirivimab solution and imdevimab solution: If immediate administration not possible, may store in a refrigerator (2–8°C) for up to 36 hours or at room temperature (up to 25°C) for up to 4 hours.

Undiluted solutions for sub-Q injection in syringes containing total dose of co-formulated solution or syringes containing total dose of casirivimab solution and syringes containing total dose of imdevimab solution: If immediate administration not possible, may store prefilled syringes in a refrigerator (2–8°C) for up to 24 hours or at room temperature (up to 25°C) for up to 8 hours.

Compatibility

Parenteral

Solution Compatibility1

Actions and Spectrum

• Casirivimab (IgG₁κ) and imdevimab (IgG₁λ) are SARS-CoV-2-specific recombinant human monoclonal antibodies; produced using recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension cultures.

• The drugs bind to non-overlapping epitopes of the spike protein receptor-binding domain (RBD) of SARS-CoV-2 and block the spike protein from attaching to the human angiotensin-converting enzyme 2 (ACE2) receptor, thereby preventing the virus from entering cells and inhibiting viral replication.

• In an in vitro SARS-CoV-2 virus neutralization assay in Vero E6 cells, casirivimab, imdevimab, and casirivimab and imdevimab together neutralized SARS-CoV-2 (USA-WA1/2020 isolate) with estimated 50% effective concentrations (EC₅₀s) of 0.006, 0.006, and 0.005 mcg/mL, respectively.

• In a treatment model in rhesus macaques, casirivimab and imdevimab given together 1 day after infection resulted in approximately a 1- to 2-log₁₀ reduction in genomic and sub-genomic viral RNA in nasopharyngeal and oral swabs obtained at day 4 in most animals, and reduced lung pathology relative to placebo-treated animals. In hamsters, casirivimab and imdevimab given together 1 day after infection resulted in reduced weight loss relative to placebo-treated animals. Clinical relevance of these findings from animal models not known.

• In a prophylaxis model in rhesus macaques, casirivimab and imdevimab given prior to challenge with SARS-CoV-2 reduced viral RNA in nasopharyngeal and oral swabs and bronchioalveolar lavage fluid and was associated with reduced lung inflammation. In a prophylaxis model in hamsters, casirivimab and imdevimab given prior to challenge with SARS-CoV-2 protected against weight loss, reduced the percentage of lung area showing pneumonia pathology, and was associated with reduced lung inflammation severity. Clinical relevance of these findings from animal models not known.

• There is a potential risk of treatment failure due to development of viral variants resistant to casirivimab and imdevimab.

• Interim data from a clinical trial evaluating casirivimab and imdevimab for treatment of mild to moderate COVID-19 in outpatients (COV-2067) indicated only one variant (G446V) occurring at an allele fraction at least 15%, which was detected in 3 of 66 patients who had nucleotide sequencing data available. In a neutralization assay using vesicular stomatitis virus (VSV) pseudotyped virus-like particles (VLP), the G446V variant had reduced susceptibility (135-fold) to imdevimab alone compared with wild type, but retained susceptibility to casirivimab alone and casirivimab and imdevimab together.

• Escape variants were identified following 2 passages in cell culture of recombinant VSV encoding SARS-CoV-2 spike protein in the presence of either casirivimab or imdevimab alone, but not following 2 passages in the presence of casirivimab and imdevimab together. Variants with reduced susceptibility to casirivimab alone included those with spike protein amino acid substitutions K417E (182-fold), K417N (7-fold), K417R (61-fold), Y453F (>438-fold), L455F (80-fold), E484K (25-fold), F486V (>438-fold), and Q493K (>438-fold). Variants with reduced susceptibility to imdevimab alone included those with amino acid substitutions K444N (>755-fold), K444Q (>548-fold), K444T (>1033-fold), and V445A (548-fold). Variants with reduced susceptibility to casirivimab and imdevimab together included those with amino acid substitutions K444T (6-fold) and V445A (5-fold).

• Data from in vitro neutralization assays indicate that casirivimab and imdevimab individually and together retained neutralization activity against pseudotyped VLP expressing all spike protein substitutions found in the SARS-CoV-2 B.1.1.7 lineage (first detected in UK; labeled Alpha by WHO) and against pseudotyped VLP expressing only the N501Y substitution found in B.1.1.7 and other circulating lineages. Casirivimab and imdevimab together retained neutralization activity (≤2-fold reduced susceptibility) against pseudotyped VLP expressing all the spike protein substitutions or individual substitutions K417N, E484K, or N501Y found in the B.1.351 lineage (first detected in South Africa; labeled Beta by WHO) and retained activity against all the spike protein substitutions or the key substitutions K417T, E484K, or N501Y found in the P.1 lineage (first detected in Brazil; labeled Gamma by WHO); however, casirivimab alone, but not imdevimab alone, had reduced activity against pseudotyped VLP expressing K417N or E484K. The E484K substitution is also found in the B.1.526 lineage (first detected in New York; labeled Iota by WHO). Casirivimab and imdevimab, individually and together, retained neutralization activity against the L452R substitution found in the B.1.427/B.1.429 lineages (first detected in California; labeled Epsilon by WHO). C Casirivimab and imdevimab, individually and together, retained neutralization activity against pseudotyped VLP expressing L452R+T478K substitutions found in the B.1.617.2 and AY.3 lineages (Delta). The drugs together retained neutralization activity against pseudotyped VLP expressing L452R+E484Q substitutions found in the B.1.617.1/B.1.617.3 lineages (first detected in India; labeled Kappa/no designation by WHO), although casirivimab alone, but not imdevimab alone, had reduced activity against pseudotyped VLP expressing L452R+E484Q. Casirivimab and imdevimab together retained activity against pseudotyped VLP expressing R346K+E484K+N501Y found in the B.1.621/B.1.621.1 (Mu) lineage, although casirivimab alone, but not imdevimab alone, had reduced activity against pseudotyped VLP expressing R346K+E484K+N501Y. Casirivimab and imdevimab, individually and together, demonstrated reduced neutralization activity against pseudotyped VLP expressing the full spike protein sequence of the B.1.1.529/BA.1 (Omicron) lineage.

• Due to the large reduction of pseudotyped VLP neutralization activity against spike protein from the B.1.1.529/BA.1 (Omicron) variant, it is unlikely that casirivimab and imdevimab together will be active against this variant.

• Casirivimab and imdevimab together retained activity against authentic SARS-CoV-2 variants of B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.1 (Kappa) lineages, although casirivimab alone, but not imdevimab, had reduced activity against B.1.351 (5-fold), P.1 (>371-fold) and B.1.617.1 (6-fold) variants.

• Some data regarding in vitro susceptibility of SARS-CoV-2 variants to casirivimab and imdevimab also are available from a plaque reduction assay that used authentic SARS-CoV-2 variants. In this assay, casirivimab and imdevimab together retained activity against authentic SARS-CoV-2 variants of B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa) lineages, although casirivimab alone, but not imdevimab alone, had reduced activity against B.1.351 (5-fold) and B.1.617.1 (6-fold) variants. Confirmatory sequencing of each of the tested isolates not completed to date.

• Not known how pseudotyped VLP or authentic SARS-CoV-2 data correlate with clinical outcomes.

• Although clinical impact not known, casirivimab and imdevimab resistance-associated variants could have cross-resistance to other SARS-COV-2-specific monoclonal antibodies that target the RBD of the virus.

Advice to Patients

• The Fact Sheet for Patients, Parents, and Caregivers: Emergency Use Authorization (EUA) of REGEN-COV (casirivimab and imdevimab) for Coronavirus Disease 2019 (COVID-19) must be provided to patients or parent/caregivers prior to administration of casirivimab and imdevimab.

• Inform patients or parent/caregivers that FDA authorized the emergency use of casirivimab and imdevimab, which is an investigational drug regimen that has not received FDA approval, for treatment of mild to moderate COVID-19 or for postexposure prophylaxis of COVID-19 in certain adults and pediatric patients who are at high risk for progressing to severe COVID-19, including hospitalization or death.

• Inform patients or parent/caregivers that they have the option to accept or refuse casirivimab and imdevimab.

• Provide patients or parent/caregivers with information on available alternative treatments and the risks and benefits of those alternatives, including clinical trials.

• Inform patients or parent/caregivers about the significant known and potential risks and benefits of casirivimab and imdevimab, and the extent to which such risks and benefits are unknown.

• Advise patients who receive casirivimab and imdevimab for treatment or postexposure prophylaxis of COVID-19 that they should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, socially distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, wash hands frequently) according to CDC guidelines.

• Importance of informing clinicians if patient has any allergies or had a severe allergic reaction, including anaphylaxis, after a prior dose of casirivimab and imdevimab.

• Importance of informing clinicians if patient has received a COVID-19 vaccine. Advise patients that casirivimab and imdevimab does not replace vaccination against COVID-19.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Casirivimab and imdevimab are not commercially available. FDA issued an EUA for casirivimab and imdevimab that allows combined use of the drugs for treatment of mild to moderate COVID-19^† or for postexposure prophylaxis of COVID-19^† in certain adults and pediatric patients at high risk for progressing to severe COVID-19, including hospitalization or death. Allocation and distribution of casirivimab and imdevimab for use under the EUA is being directed by the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) in collaboration with state and territorial health departments and the manufacturer. Healthcare facilities can contact the authorized US distributor (AmerisourceBergen) directly to obtain casirivimab and imdevimab for use under the EUA. Information on specific locations in the US administering casirivimab and imdevimab may be available at the HHS protect public data hub ([Web]) or National Infusion Center Association (NICA) website ([Web]).

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