casirivimab/imdevimab (Investigational)

Brand and Other Names:REGEN-COV
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

Available as

  • Single vial which contains 2 antibodies coformulated in a 1:1 ratio, OR
  • Individual antibody solution in separate vials (supplied separately or in a dose pack)

injection, solution

  • Casirivimab/imdevimab (600mg/600mg) per 10mL vial
  • Casirivimab 1200mg/10mL vial; 300mg/2.5mL vial
  • Imdevimab 1200mg/10mL vial; 300mg/2.5mL vial

COVID-19 (EUA)

November 21, 2020: Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients aged ≥12 years 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

IV infusion strongly recommended; SC injection is an alternative route of administration when IV infusion is not feasible and would lead to delay in treatment

IV: Casirivimab 600 mg and imdevimab 600 administered together as a single IV infusion; must dilute before IV infusion

SC: Casirivimab 600 mg and imdevimab 600 mg SC

Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization

Dosage Modifications

Renal impairment

  • Not eliminated intact in urine, thus renal impairment is not expected to affect systemic exposure

Hepatic impairment

  • Unknown

Dosing Considerations

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies

Limitations of use

  • Benefit of treatment not been observed in patients hospitalized due to COVID-19
  • Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
  • 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 long-term oxygen therapy due to underlying non-COVID-19-related comorbidity

Patient selection

Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of casirivimab and imdevimab under the EUA is not limited to the medical conditions or factors listed below

  • Medical conditions or other factors placing patients at higher risk for progressing to severe COVID-19
    • Older age (eg, ≥65 yr)
    • Obesity/overweight (BMI ≥25 kg/m2 [adults]; BMI ≥85th percentile for age/gender based on CDC growth charts [if aged 12-17 yr])
    • Pregnancy
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or immunosuppressive treatment
    • Cardiovascular disease (including congenital heart disease) or hypertension
    • Chronic lung diseases (eg, COPD, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
    • Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive pressure ventilation [not related to COVID 19])
    • EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website

Dosage Forms & Strengths

Available as

  • Single vial which contains 2 antibodies coformulated in a 1:1 ratio, OR
  • Individual antibody solution in separate vials (supplied separately or in a dose pack)

injection, solution

  • Casirivimab/imdevimab (600mg/600mg) per 10mL vial
  • Casirivimab 1200mg/10mL vial; 300mg/2.5mL vial
  • Imdevimab 1200mg/10mL vial; 300mg/2.5mL vial

November 21, 2020: Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients aged ≥12 years 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

IV infusion strongly recommended; SC injection is an alternative route of administration when IV infusion is not feasible and would lead to delay in treatment

Casirivimab 600 mg and imdevimab 600 administered together as a single IV infusion; must dilute before IV infusion

SC: Casirivimab 600 mg and imdevimab 600 mg SC

Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization

Dosage Modifications

Renal impairment

  • Not eliminated intact in urine, thus renal impairment is not expected to affect systemic exposure

Hepatic impairment

  • Unknown

Dosing Considerations

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies

Limitations of use

  • Benefit of treatment not been observed in patients hospitalized due to COVID-19
  • Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
  • 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 long-term oxygen therapy due to underlying non-COVID-19-related comorbidity

Patient selection

Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of casirivimab and imdevimab under the EUA is not limited to the medical conditions or factors listed below

  • Medical conditions or other factors placing patients at higher risk for progressing to severe COVID-19
    • BMI ≥85th percentile for age/gender based on CDC growth charts [if aged 12-17 yr])
    • Pregnancy
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or immunosuppressive treatment
    • Cardiovascular disease (including congenital heart disease) or hypertension
    • Chronic lung diseases (eg, COPD, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
    • Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive pressure ventilation [not related to COVID 19])
    • EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website
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Adverse Effects

>10%

SC

  • Injection site reactions (12%)

1-10%

IV

  • Infusion-related reactions (1.5%)

Frequency Not Defined

IV or SC

  • Pneumonia
  • Hyperglycemia
  • Nausea
  • Vomiting
  • Intestinal obstruction
  • Dyspnea
  • Anaphylactic reactions
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Warnings

Contraindications

None

Cautions

Hypersensitivity

  • Potential for serious hypersensitivity reaction, including anaphylaxis
  • If signs and symptoms occur, immediately discontinue IV infusion and initiate appropriate medications and/or supportive care
  • Infusion-related reactions reported, including fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness

Severe COVID-19

  • Treatment benefit not observed in patients hospitalized due to COVID-19
  • Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
  • Therefore, casirivimab and imdevimab are 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 long-term oxygen therapy due to underlying non-COVID-19-related comorbidity

Viral variants

  • Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies
  • Prescribing clinicians should consider prevalence of casirivimab/imdevimab resistant variants in their area
  • Health care providers should review antiviral resistance information provided by state and local health departments
  • Variant proportions circulating in the US can be monitored at the CDC website
  • Fold-reduction in susceptibility May 2021
    • Casirivimab and imdevimab together retained neutralization activity against pseudovirus expressing all spike protein substitutions tested
    • B.1.1.7 (UK origin): No change
    • B.1.351 (South Africa origin): No change
    • P.1 (Brazil origin): No change
    • B.1.427/B.1.429 (California origin): No change
    • B.1.526 (New York origin): No change

Drug interaction overview

  • Not renally excreted or metabolized by CYP450 enzymes
  • Interactions with concomitant renally excreted drugs or drugs that are CYP450 substrates, inducers, or inhibitors are unlikely
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Pregnancy & Lactation

Pregnancy

Insufficient data to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Use during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus

Lactation

Data are unknown regarding presence in human or animal milk, effects on breastfed infants, or effects on milk production

Maternal IgG is known to be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Casirivimab (IgG1-kappa) and imdevimab (IgG1-lambda) are recombinant human mAbs, which are unmodified in the Fc regions

The mAbs bind to nonoverlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2, and thereby block binding to the human ACE2 receptor

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Administration

IV Compatibilities

0.9% NaCl

Preparation

IV

Casirivimab and imdevimab IV solution are each supplied in individual single-dose vials and must be diluted before administration

Remove vials from refrigerated storage and allow to equilibrate to room temperature for ~20 minutes before preparation

Do not expose to direct heat; do not shake vials

Inspect for particulate matter and discoloration; solution should appear clear to slightly opalescent and colorless to pale yellow

Obtain prefilled IV bag containing 50 mL, 100 mL, 150 mL, or 250 mL of 0.9% NaCl

  • Using coformulated vial
    • Add 10 mL into infusion bag containing 0.9% NaCl
  • Using individual vials
    • Add casirivimab 600 mg (5 mL) and imdevimab 600 mg (5 mL) from each respective vial using separate syringes and inject all 10 mL into the infusion bag containing 0.9% NaCl

Discard any product remaining in the vial

Gently invert infusion bag by hand ~10 times to mix; do not shake

This product is preservative-free and therefore, diluted infusion solution should be administered immediately; if immediate administration is not possible, refrigerate diluted casirivimab and imdevimab infusion solution

SC

Remove vial(s) from refrigerated storage and allow to equilibrate to room temperature for ~20 minutes before preparation

Do not expose to direct heat

Do not shake the vials

For the administration of 600 mg of casirivimab and 600 mg of imdevimab, gather 4 syringes and prepare for SC injections

  • Using coformulated vial
    • Withdraw 2.5 mL solution per syringe into 4 separate syringes
  • Using individual vials
    • Casirivimab: Withdraw 2.5 mL per syringe into 2 separate syringes
    • Imdevimab: Withdraw 2.5 mL per syringe into 2 separate syringes

Replace the 21-gauge transfer needle with a 25-gauge or 27-gauge needle for SC injection

IV Administration

If refrigerated, allow diluted solution to equilibrate to room temperature for ~30 minutes before infusing

Infuse by PVC infusion set containing 0.20/0.22-micron in-line polyethersulfone (PES) filter

Attach infusion set to IV bag and prime infusion set

Maximum infusion rate

  • 50-mL bag: 210 mL/hr (minimum time: 20 min)
  • 100-mL bag: 310 mL/hr (minimum time: 23 min)
  • 150-mL bag: 310 mL/hr (minimum time: 33 min)
  • 250-mL bag: 310 mL/hr (minimum time: 52 min)

Flush line after infusion completed to ensure entire dose delivered

Discard unused product

Monitor during infusion and observe patients for at least 1 hr after infusion completed

SC Administration

Administer the 4 prepared SC injections consecutively, each at different injection sites, into thigh, back of upper arm, or abdomen, except for 2 inches (5 cm) around the navel; avoid waistline

Use different quadrants of abdomen or upper thighs or back of upper arms to space apart each 2.5 mL SC injection

DO NOT inject into skin that is tender, damaged, bruised, or scarred

Clinically monitor patients after injections and observe for at least 1 hr

Storage

Preservative-free product

Unopened vials

  • Refrigerate unopened vials at 2-8ºC (36-46ºF) in original carton to protect from light
  • Do not freeze, shake, or expose to direct light

Diluted solution

  • Refrigerate at 2-8ºC (36-46ºF) for no more than 36 hr OR
  • Store at room temperature up to 25ºC (77ºF) for no more than 4 hr
  • These storage times include infusion time

Prepared SC syringes

Refrigerate at 2-8ºC (36-46ºF) for no more than 4 hr OR

Store at room temperature up to 25ºC (77ºF) for no more than 4 hr

If refrigerated, allow the syringes to equilibrate to room temperature for ~20 minutes before administration

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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.