Casirivimab + Imdevimab (Investigational)

Casirivimab + Imdevimab (Investigational) is used for: COVID-19 infection

Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults 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 Adult Injection 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 Hepatic impairment Unknown

Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in 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 Child Injection 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

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

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 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

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 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

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

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

Side effects of Casirivimab + Imdevimab (Investigational) : 1-10% Infusion-related reactions (1.5%) Frequency Not Defined Pneumonia Hyperglycemia Nausea Vomiting Intestinal obstruction Dyspnea

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