casirivimab/imdevimab (Investigational)

Brand and Other Names:REGEN-COV
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

IV solution

  • Casirivimab 1200mg/10mL vial
  • Imdevimab 1200mg/10mL vial
  • Further dilution required

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

Casirivimab 1200 mg and imdevimab 1200 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 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

  • High risk defined as meeting at least 1 of these criteria
    • BMI ≥35
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease
    • Receiving immunosuppressive treatment
    • Age ≥65 years
    • Age ≥55 years and have cardiovascular disease, hypertension, or COPD/chronic respiratory disease
  • Additional high-risk factors in patients aged 12-17 years
    • BMI ≥85th percentile for their age and sex based on CDC growth charts
    • Sickle cell disease
    • Congenital or acquired heart disease
    • Neurodevelopmental disorders (eg, cerebral palsy)
    • Medical-related technological dependence (eg, tracheostomy, gastrostomy, positive-pressure ventilation [not related to COVID-19])
    • Asthma, reactive airway disease, or other chronic respiratory disease requiring daily medication for control

Dosage Forms & Strengths

IV solution

  • Casirivimab 1200mg/10mL vial
  • Imdevimab 1200mg/10mL vial
  • Further dilution required

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

Casirivimab 1200 mg and imdevimab 1200 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 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

  • High risk defined as meeting at least 1 of these criteria
    • BMI ≥35
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease
    • Receiving immunosuppressive treatment
  • Additional high-risk factors in patients aged 12-17 years
    • BMI ≥85th percentile for their age and sex based on CDC growth charts
    • Sickle cell disease
    • Congenital or acquired heart disease
    • Neurodevelopmental disorders (eg, cerebral palsy)
    • Medical-related technological dependence (eg, tracheostomy, gastrostomy, positive-pressure ventilation [not related to COVID-19])
    • Asthma, reactive airway disease, or other chronic respiratory disease requiring daily medication for control
Next:

Adverse Effects

1-10%

Infusion-related reactions (1.5%)

Frequency Not Defined

Pneumonia

Hyperglycemia

Nausea

Vomiting

Intestinal obstruction

Dyspnea

Previous
Next:

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 March 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
Previous
Next:

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.

Previous
Next:

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

Previous
Next:

Administration

IV Compatibilities

0.9% NaCl

IV Preparation

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

Add casirivimab 1200 mg (10 mL) and imdevimab 1200 mg (10 mL) from each respective vial using 2 separate syringes and inject all 20 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

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

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
Previous
Next:

Images

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