For U.S. Healthcare Professionals only

For U.S. Patients and Caregivers only

REGEN-COV™ (casirivimab with imdevimab)

REGEN-COV (casirivimab with imdevimab to be administered together) has not been approved, but has been authorized for emergency use by FDA, for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.

This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Food Drug and Cosmetic Act, unless the authorization is terminated or revoked sooner.

Dosing and Administration

The recommended dose of REGEN-COV under the EUA is 1200 mg of casirivimab and 1200 mg of imdevimab administered as a single intravenous (IV) infusion over at least 60 minutes.

The optimal dosing regimen for treatment for COVID-19 has not yet been established. The recommended dosing regimen may be updated as data from clinical trials becomes available.

The recommended dose for treatment are shown in the table below.

CASIRIVIMAB WITH IMDEVIMAB MUST BE ADMINISTERED TOGETHER AFTER DILUTION BY INTRAVENOUS (IV) INFUSION ONLY.

Casirivimab and imdevimab solutions must be diluted prior to administration.

Casirivimab and imdevimab should be given together as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset. For more information on high risk patients, please view the HCP fact sheet.

Each REGEN-COV dose pack contains sufficient number of vials of casirivimab (REGN10933) and imdevimab (REGN10987) to prepare one treatment dose. Note that casirivimab and imdevimab vial labels and carton labeling may instead be labeled REGN10933 and REGN10987 respectively.

Table 1: Recommended Dilution Instructions for Casirivimab with Imdevimab for IV Infusion

Casirivimab with Imdevimab
2400 mg Dosea
Antibody Dose Volume to Withdraw from Vial Number of Vials Neededb Maximum Infusion Rate Minimum Infusion Time
Casirivimab
REGN10933 1,200 mg
10 mL 1 vial of 11.1 mL
OR
4 vials of 2.5 mL
250 mL/hr 60 minutes
Imdevimab
REGN10987 1,200 mg
10 mL 1 vial of 11.1 mL
OR
4 vials of 2.5 mL

NOTE: casirivimab = REGN10933; imdevimab = REGN10987

a 1,200 mg of Casirivimab and 1,200 mg of Imdevimab are to be administered together as a single intravenous infusion for a combined 2,400 mg dose.
b One 11.1 mL vial of one antibody may be prepared with four 2.5 mL vials of the other antibody to create one treatment course

Dosage forms and strengths

Antibody Dosage Form Vial Sizes
Casirivimab Solution for Injection 1332 mg/11.1 mL (120 mg/mL)
and
300 mg/2.5 mL (120 mg/mL)
Imdevimab Solution for Injection 1332 mg/11.1mL (120 mg/mL)
and
300 mg/2.5 mL (120 mg/mL)

NOTE: casirivimab = REGN10933; imdevimab = REGN10987

Dose Preparation and Administration

Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Should either be observed, the solution should be discarded and fresh solution prepared.

Important Preparation and Administration Instructions

Preparation

Casirivimab and imdevimab are each supplied in individual single-dose vials, and must be diluted prior to administration.

Casirivimab with imdevimab solution for infusion should be prepared by a qualified healthcare professional using aseptic technique:

  1. Remove the casirivimab and imdevimab vials from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake the vials.
  2. Inspect casirivimab and imdevimab vials visually for particulate matter and discoloration prior to administration. Should either be observed, the solution must be discarded, and fresh solution prepared. The solution for each vial should be clear to slightly opalescent, colorless to pale yellow.
  3. Obtain a pre-filled IV infusion bag containing 250 mL of 0.9% Sodium Chloride Injection.
  4. Withdraw 10 mL of casirivimab and 10 mL of imdevimab from each respective vial using two separate syringes and inject all 20 mL into a prefilled infusion bag containing 0.9% Sodium Chloride Injection, see Table 1. Discard any product remaining in the vial.
  5. Gently invert infusion bag by hand approximately 10 times to mix. Do not shake. This product is preservative-free and therefore, the diluted infusion solution should be administered immediately. If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution in the refrigerator between 2°C to 8°C (36°F to 46°F) for no more than 36 hours or at room temperature up to 25°C (77°F) for no more than 4 hours. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration.

Each REGEN-COV dose pack contains sufficient number of vials of casirivimab and imdevimab to prepare one treatment dose. Vials should remain in the dose pack until time of preparation of the IV solution.

Administration

Casirivimab with imdevimab infusion solution should be administered by a qualified healthcare professional using aseptic technique.

  • Gather the recommended materials for infusion:
    • Polyvinyl chloride (PVC), polyethylene (PE)-lined PVC, or polyurethane (PU) infusion set
  • In-line or add-on 0.2 micron polyethersulfone (PES) filter
  • Attach the infusion set to the IV bag.
  • Prime the infusion set.
  • Administer the entire infusion solution in the bag via pump or gravity over at least 60 minutes through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone (PES) filter (see Table 1). Due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage.
  • The prepared infusion solution should not be administered simultaneously with any other medication. The compatibility of casirivimab and imdevimab with IV solutions and medications other than 0.9% Sodium Chloride Injection is not known.
  • After infusion is complete, flush the tubing with 0.9% Sodium Chloride Injection to ensure delivery of the required dose.
  • Discard unused product.
  • Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete.

Storage

This product is preservative-free and therefore, the diluted infusion solution should be administered immediately. If immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution in the refrigerator between 2°C to 8°C (36°F to 46°F) for no more than 36 hours or at room temperature up to 25°C (77°F) for no more than 4 hours. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration.

Click here for dose preparation instructions for casirivimab and imdevimab, and here for additional guidance on preparation.

Use in Specific Populations

Use in Pregnancy

Risk Summary

There is currently limited clinical experience in the use of casirivimab and imdevimab in COVID-19 patients who are pregnant. IgG1 antibodies being known to cross the placental barrier and it being unknown whether potential transfer provides any treatment benefit or risk to the developing fetus. Casirivimab and imdevimab therapy should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

Use in Nursing Mothers

Risk Summary

There are no available data on the presence of casirivimab and/or imdevimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for casirivimab and imdevimab and any potential adverse effects on the breastfed child from casirivimab and imdevimab or from the underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

Pediatric Use

The safety and effectiveness of REGEN-COV has not been assessed in pediatric patients. The recommended dosing regimen is expected to result in comparable serum exposures of casirivimab and imdevimab in patients 12 years of age and older and weighing at least 40 kg as observed in adults, since adults with similar body weight have been included in Trial R10933-10987-COV-2067.

Geriatric Use

Of the 799 patients with SARS-CoV-2 infection randomized in Trial R10933-10987-COV-2067, 7% were 65 years or older, and 2% were 75 years of age or older. The difference in PK of casirivimab and imdevimab in geriatric patients compared to younger patients is unknown.

Renal Impairment

Casirivimab and imdevimab are not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of casirivimab and imdevimab.

Hepatic Impairment

The effect of hepatic impairment on PK of casirivimab and imdevimab is unknown.

Links/attachments

Drug Administration Coding Reference sheet
FDA Letter of Authorization
HCP Fact Sheet (English)
HCP Fact Sheet (Spanish)
Patient Fact Sheet (English)
Patient Fact Sheet (Spanish)
Dear Healthcare Provider Letter
REGEN-COV EUA Guidebook
HHS Factsheet: Monoclonal Antibody Treatment for High Risk COVID-19 Positive Patients

Regeneron is working closely with health authorities and is focused on contributing our infectious disease expertise and resources to help patients and communities impacted by COVID-19.

IMPORTANT SAFETY INFORMATION

REGEN-COV (casirivimab with imdevimab) is an unapproved investigational therapy, and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use.

  • Warnings and Precautions
    • Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV (casirivimab with imdevimab). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions have been observed with administration of REGEN-COV. These reactions may be severe or life threatening.
      • Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, fatigue and diaphoresis. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care
    • Clinical Worsening After REGEN-COV Administration: Clinical worsening of COVID-19 after administration of REGEN-COV has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to REGEN-COV use or were due to progression of COVID-19
    • Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high-flow oxygen or mechanical ventilation with COVID-19. Therefore, REGEN-COV is not authorized for use in patients who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19, OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19–related comorbidity
  • Adverse Reactions:
    • Serious adverse events (SAEs) were reported in 4 (1.6%) patients in the REGEN-COV 2,400-mg group, 2 (0.8%) patients in the REGEN-COV 8,000-mg group, and 6 (2.3%) patients in the placebo group. None of the SAEs were considered to be related to study drug. SAEs that were reported as Grade 3 or 4 adverse events were pneumonia, hyperglycemia, nausea and vomiting (2,400 mg REGEN-COV), intestinal obstruction and dyspnea (8,000 mg REGEN-COV) and COVID-19, pneumonia and hypoxia (placebo). REGEN-COV is not authorized at the 8,000-mg dose (4,000 mg casirivimab and 4,000 mg imdevimab)
    • One anaphylactic reaction was reported in the clinical program. The event began within 1 hour of completion of the infusion, and required treatment including epinephrine. The event resolved. Infusion-related reactions, of Grade 2 or higher severity, were reported in 4 subjects (1.5%) in the 8,000-mg (4,000 mg casirivimab and 4,000 mg imdevimab) arm. These infusion-related reactions events were moderate in severity; and included pyrexia, chills, urticaria, pruritus, abdominal pain, and flushing. One infusion-related reaction (nausea) was reported in the placebo arm, and none were reported in the 2,400-mg (1,200 mg casirivimab and 1,200 mg imdevimab) arm. In two subjects receiving the 8,000-mg dose of REGEN-COV, the infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting) resulted in permanent discontinuation of the infusion. All events resolved.
  • Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete
  • Use in Specific Populations:
    • Pregnancy: There is currently limited clinical experience in the use of REGEN-COV in COVID-19 patients who are pregnant. REGEN-COV therapy should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus
    • Nursing Mothers: There is currently no clinical experience in the use of REGEN-COV in COVID-19 patients who are breastfeeding. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for REGEN-COV and any potential adverse effects on the breastfed child from REGEN-COV or from the underlying maternal condition

AUTHORIZED USE

REGEN-COV (casirivimab with imdevimab to be administered together) is authorized for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization. [see Limitations of Authorized Use]

  • REGEN-COV has not been approved, but has been authorized for emergency use by FDA
  • This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner
  • Healthcare providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of REGEN-COV and mandatory requirements of the EUA and must comply with the requirements of the EUA. The FDA Letter of Authorization is available for reference, as well as the Dear Healthcare Provider Letter and Patient Fact Sheet

Limitations of Authorized Use:

  • REGEN-COV (casirivimab with imdevimab) is not authorized for use in patients:
    • who are hospitalized due to COVID-19, OR
    • who require oxygen therapy due to COVID-19, OR
    • who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.
  • Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation

Definition of High Risk Patients

High risk is defined as patients who meet at least one of the following criteria:

  • Have a body mass index (BMI) ≥35
  • Have chronic kidney disease
  • Have diabetes
  • Have immunosuppressive disease
  • Are currently receiving immunosuppressive treatment
  • Are ≥65 years of age
  • Are ≥55 years of age AND have
    • cardiovascular disease, OR
    • hypertension, OR
    • chronic obstructive pulmonary disease/other chronic respiratory disease
  • Are 12–17 years of age AND have
    • BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/​growthcharts/​clinical_charts.htm, OR
    • sickle cell disease, OR
    • congenital or acquired heart disease, OR
    • neurodevelopmental disorders (e.g. cerebral palsy), OR
    • a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
    • asthma, reactive airway or other chronic respiratory disease that requires daily medication for control

ADDITIONAL INFORMATION FOR HEALTHCARE PROVIDERS

  • Casirivimab and imdevimab are each provided in a separate carton and vial. Casirivimab and imdevimab vial labels and carton labeling may instead be labeled REGN10933 and REGN10987, respectively.
  • Each REGEN-COV dose pack contains sufficient number of vials of casirivimab (REGN10933) and imdevimab (REGN10987) to prepare one treatment dose.
  • You may receive cartons and vials of casirivimab and imdevimab that are labeled "for intravenous infusion or subcutaneous injection." However, casirivimab and imdevimab must be administered together (although packaged separately) after dilution by intravenous (IV) infusion only
  • Store casirivimab and imdevimab together in inventory. See www.regeneroneua.com/access for images of packaging
  • REGEN-COV may only be administered in settings in which healthcare 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
  • The recommended dose is 1200 mg of casirivimab with 1200 mg of imdevimab administered as a single intravenous infusion over at least 60 minutes as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset. Since the optimal dosing regimen has not yet been established, it might be updated as data become available. See the Fact Sheet for Healthcare Providers for complete dosage, preparation, and administration instructions
  • The prescribing healthcare provider and/or the provider's designee are responsible for mandatory reporting of all medication errors and ALL SERIOUS ADVERSE EVENTS potentially related to REGEN-COV. These adverse events must be reported within 7 calendar days from the onset of the event
  • Healthcare facilities and providers must report therapeutics information and demonstrate adequate utilization via data reported through HHS Protect, Teletracking or National Healthcare Safety Network (NHSN) as directed by the U.S. Department of Health and Human Services
  • MedWatch adverse event reports can be submitted to the FDA here, by using a postage-paid Form FDA 3500 and returning by mail/fax, or by calling 1-800-FDA-1088 to request a reporting form. In addition, please provide a copy of all FDA MedWatch forms to Regeneron Pharmaceuticals, Inc via fax (1-888-876-2736) or email ([email protected]​regeneron.com)

IMPORTANT SAFETY INFORMATION

REGEN-COV (casirivimab with imdevimab) is an unapproved investigational therapy, and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use.

  • Warnings and Precautions
    • Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions,

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