REGEN-COV, Casirivimab + Imdevimab

REGEN-COV
  • Casirivimab and Imdevimab (REGEN-COV) are monoclonal antibodies that specifically block two areas of the spike protein of SARS-CoV-2  and, hence, infectivity of the virus.
  • No activity vs. Omicron variant, hence, DO NOT USE.
  • Among seronegative patients, median time to symptom alleviation (defined as symptoms becoming mild or absent) was 13 days in placebo, 6-8 days with the monoclonal combination. Those with high viral loads at baseline had the most benefit in terms of time to symptom alleviation. 
    • Serious adverse events occurred in 2 placebo patients, 1 low dose patient and no high dose patients. There were no deaths in the trial.
  • The FDA issued an Emergency Use Authorization (EUA) letter on 21 Nov 2020 (updated 3 June 2021) for treatment of mild to moderate COVID-19 in adults and children (age ≥12 years, wt ≥40 kg) with positive results of direct SARS-CoV-2 testing, who are at high risk for progression to severe COVID-19, including hospitalization or death.
  • On June 3, 2021, the FDA issued significant updates to the EUA. These updates include:
    • Lowering the authorized dosage to 600 mg of casirivimab and 600 mg of imdevimab, administered together.
    • Addition of subcutaneous (sc) administration as an alternative route when IV infusion is not feasible and would result in treatment delay.
    • A co-formulated product in a single vial. Each 10 mL vial contains 600 mg of casirivimab and 600 mg of imdevimab.
  • Not authorized for use in patients:
    • Who are hospitalized due to COVID-19.
    • Who require oxygen therapy due to COVID-19.
    • Who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy.
  • On November 17, 2021, the FDA further revised the EUA, authorizing casirivimab and imdevimab (subcutaneously) for emergency use as post-exposure prophylaxis for COVID-19 in adults and pediatric individuals (age ≥12 years, wt ≥40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death. It is not authorized for pre-exposure prophylaxis. It should only be used as post-exposure prophylaxis for individuals who are not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination.
  • Treatment dose: Casirivimab 600 mg + Imdevimab 600 mg administered together as a single IV infusion (or by sc injection). Intravenous infusion is strongly recommended.
  • Post-exposure prophylaxis dose: Casirivimab 600 mg + Imdevimab 600 mg administered together as a single IV infusion (or by sc injection) as soon as possible following exposure to SARS-CoV-2. For individuals in whom repeat dosing is determined to be appropriate for ongoing exposure to SARS-CoV-2 for >4 weeks and who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination, the initial dose is followed by subsequent repeat dosing of 300 mg of casirivimab and 300 mg of imdevimab by sc injection or IV infusion once every 4 weeks for the duration of ongoing exposure.
  • Preparation (of treatment dose or initial PEP dose) for IV infusion:
    • Allow vial(s) to equilibrate to room temperature for 20 minutes. Do not expose to direct heat, do not shake.
    • Add 600 mg of each antibody to an infusion bag of NS (choose between 50, 100, 150, and 250 mL). If using co-formulated product, add the entire vial. If using individually packaged antibodies, note the antibody concentration in each vial (120 mg/mL). Administered diluted infusion solution immediately.
    • Infuse IV through a 0.2-micron filter using these minimum infusion times:
      • 50 mL bag: 20 minutes (max infusion rate 180 mL/hr)
      • 100 mL bag: 21 minutes (max infusion rate 310 mL/hr)
      • 150 mL bag: 31 minutes (max infusion rate 310 mL/hr)
      • 250 mL bag: 50 minutes (max infusion rate 310 mL/hr)
  • Preparation (of treatment dose or initial PEP dose) for sc injection:
    • Allow vial(s) to equilibrate to room temperature for 20 minutes. Do not expose to direct heat, do not shake.
    • If using co-formulated product, prepare four syringes (150 mg/150 mg per 2.5 mL each).
    • If using individually packaged antibodies, prepare two syringes of casirivimab (300 mg/2.5 mL each) and two syringes of imdevimab (300 mg/2.5 mL each).
    • Use prepared syringes immediately. Administer the sc injections consecutively, each at a different injection site, into the thigh, back of the upper arm, or abdomen.
  • Age ≥12 years, weight ≥40 kg: same as adult dose.
  • No adjustment recommended.
  • The effect of hepatic impairment on the pharmacokinetics of casirivimab and imdevimab is unknown.
  • Monitor patients during infusion and for at least one hour after infusion is complete.
  • Infusion-related adverse effects:
    • Fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness.
  • Serious hypersensitivity reaction, including anaphylaxis.
  Casirivimab Imdevimab
 Class IgG1 mAb IgG1 mAb
PK/PD Index No data No data
Pharmaceutical
Preparation
Injection Injection
Usual Dose  600 mg 600 mg
Pregnancy
Category
No human data No human data
Food Effect1 Not applicable Not applicable
Oral
Absorption2 (%)
Not applicable Not applicable
Peak Serum Level3
(μg/mL)
IV: 192 (end of infusion)
SC: 55.6
IV: 198 (end of infusion)
SC: 52.7
Tmax
8 days
7 days
Protein Binding
(%)
No data No data
Average Serum
Half-life4
31.8 days 26.9 days
Biliary Penetration5 (%) No data No data
CSF/Blood
Penetration6 (%)
No data No data
Therapeutic Levels in CSF7 No data No data
Volume of Distribution8
(Vd)
No data No data
AUCinf
(mg*DAY/L)
2580 1990
CYP450, Transporter
Interactions
 No known interactions No known interactions
  • Notes:
    • 1 Adult preparations unless otherwise noted.
    • 2 Absorption under optimal conditions.
    • 3 Total drug; adjust for protein binding to determine free drug concentration.
      • SD = after single dose
      • SS = steady state after multiple doses
    • 4 Assumes CrCl > 80 mL/min
    • 5 Peak concentration in bile/peak concentration in serum x 100
    • 6 CSF levels with inflammation
    • 7 Judgment based on drug dose & organism susceptibility. CSF concentration ideally ≥10x above MIC.
    • 8 Volume of Distribution (Vd):
      • V/F = Vd/oral bioavailability
      • Vss = Vd at steady state
  • No clinically significant interactions known.
  • Product availability:
    • Individually packaged antibodies: 300 mg and 1332 mg vials (both 120 mg/mL), preservative free.
    • Co-formulated: 600 mg/600 mg per 10 mL vial (60 mg/60 mg per mL), preservative free.
  • Storage: refrigerate unopened vials at 2-8ºC, protected from light.
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