Dosing & Uses
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
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
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
Adverse Effects
1-10%
Infusion-related reactions (1.5%)
Frequency Not Defined
Pneumonia
Hyperglycemia
Nausea
Vomiting
Intestinal obstruction
Dyspnea
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 H5
- 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
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
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.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
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 IV bag of 0.9% NaCl 250-mL; withdraw and discard 20 mL of 0.9% NaCl from infusion bag before adding casirivimab and imdevimab solutions
Add casirivimab 1200 mg (10 mL) and imdevimab 1200 mg (10 mL) from each respective vial using 2 separate syringes and dilute together in 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 IV over 60 minutes
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
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
