Tocilizumab

by Editorial Board last updated 2021-02-25 19:15:49.448294-05:00
IL-6 Inhibitor, Tocilizumab
Actemra
  • Tocilizumab is a recombinant humanized anti-interleukin 6 (IL-6) monoclonal antibody.
  • Tocilizumab binds to both soluble and membrane-bound IL-6 receptors, and has been shown to inhibit IL-6-mediated signaling through those receptors.
  • The most recent IDSA guidelines make a conditional recommendation, low certainty of evidence, for the use of tocilizumab in addition to standard of care, including corticosteroids, for progressive severe or critical disease in patients with COVID-19 pneumonia. Benefit probably greatest if administered early, i.e. within 48 hours of hospitalization or less than 24 hours after ICU admission.
  • Black box warning: Serious infections due to bacterial, mycobacterial, fungal, viral, or other opportunistic pathogens.
  • For COVID-19: 8 mg/kg as a single IV infusion over 60 minutes, with a second dose 12-24 hours later if no improvement.
  • Preparation:
    • Body weight <30 kg: use 50 mL bag of normal saline.
    • Body weight ≥30 kg: use 100 mL bag of normal saline.
    • Withdraw a volume of NS from the bag equal to the volume of tocilizumab (0.4 mL/kg) required for the patient's dose, then slowly add the tocilizumab. Mix by inverting the bag to avoid foaming.
  • Stability of infusion solution: 4 hours at room temperature, 24 hours at 2-8ºC.
  • Not data for pediatric patients with COVID-19.
  • Serious infections due to bacterial, mycobacterial, fungal, viral, or other opportunistic pathogens.
  • Gastrointestinal perforations.
  • Hepatotoxicity.
  • Neutropenia, thrombocytopenia.
  • Lipid abnormalities.
  • Hypersensitivity reactions, including anaphylaxis.
  • Demyelinating disorders.
  • Malignancy.
Class  IgG monoclonal antibody
PK/PD Index  No data
Pharmaceutical
Preparation
 Injectable
Usual Adult Dose  For COVID-19: 8 mg/kg IV x1, may repeat in 12-24 hours
Pregnancy Risk Summary
 Humans: insufficient data
Animals: potentially toxic to fetus
Food Effect1  Not applicable
Oral
Absorption2 (%)
 Not applicable
Peak Serum Level3
(μg/mL)
176
(8 mg/kg q4 weeks, SS)
Protein Binding
(%)
 No data
Average Serum
Half-life4
 About 21.5 days (terminal)
Biliary Penetration5 (%)  No data
CSF/Blood
Penetration6 (%)
 No data
Therapeutic Levels in CSF7  No data
Volume of Distribution8
(Vd)
6.4-7.5 L
(Vss, adults)
AUC9
(μg*hr/mL)
 No data
CYP450, Transporter
Interactions
 See Major Drug 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
      • Vss/F = Vd at steady state/oral bioavailability
    • 9 Area under the plasma concentration versus time curve
  • Hepatic CYP450 enzymes are down-regulated by infection and inflammatory stimuli, including cytokines such as IL-6. Therefore, treatment with tocilizumab may restore CYP450 activity, leading to increased metabolism (and decreased activity) of CYP450 substrates. For example, a 28% and 57% decrease in omeprazole and simvastatin exposure, respectively, has been observed one week after a single dose of tocilizumab.
  • Exercise caution when using tocilizumab in patients receiving CYP450 substrates with a narrow therapeutic index.
  • The effect of tocilizumab on CYP450 activity may persist for several weeks after stopping therapy.
  • Supplied as 80 mg/4 mL, 200 mg/10 mL, and 400 mg/20 mL single-dose vials for further dilution before IV administration.
  • Storage: 2-8ºC.