REGEN-COV, Casirivimab + Imdevimab

by Douglas Black, Pharm.D. last updated 2022-11-28 11:18:11.812530-05:00 © Antimicrobial Therapy, Inc.
REGEN-COV

Usage and Dosing

  • 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.

Adult Dose

  • 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.

Pediatric Dose

  • Age ≥12 years, weight ≥40 kg: same as adult dose.

Renal Adjustment

  • No adjustment recommended.

Hepatic Adjustment

  • The effect of hepatic impairment on the pharmacokinetics of casirivimab and imdevimab is unknown.

Adverse Effects

  • 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.

Antimicrobial Spectrum

Pharmacology

  Casirivimab Imdevimab
 Class IgG1 mAb IgG1 mAb
PK/PD Index No data No data
Pharmaceutical
Preparation		 Injection Injection
Pregnancy
Category		 No human data No human data
Food Effect1 - -
Oral
Absorption2 (%)		 - -
Peak Serum Level3
(μg/mL)
IV 192, sc 55.6
(600 mg, SD)
IV 198, sc 52.7
(600 mg, SD)
Tmax
8 days
7 days
Protein Binding
(%)		 No data No data
Average Serum
Half-life4		 31.8 days 26.9 days
Elimination Catabolized (similar to IgG) Catabolized (similar to IgG)
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
(600 mg IV, 0-inf)
1990
(600 mg IV, 0-inf)
CYP450, Transporter
Interactions		  None known None known
  • 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

Major Drug Interactions

  • No clinically significant interactions known.

Comments

  • 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.