What is the recommended Tocilizumab (Interleukin-6 receptor antagonist) dosing regimen?

Tocilizumab Dosing Regimen Recommendations

The recommended tocilizumab dosing regimen is 8 mg/kg intravenously over 1 hour (not to exceed 800 mg per dose), which can be repeated every 8 hours if no improvement is observed, with a maximum of 3 doses in 24 hours and 4 doses total. 1

Dosing Based on Clinical Indication

For Cytokine Release Syndrome (CRS)

• Grade 1 CRS (fever ≥38°C):

  • Consider 1 dose of tocilizumab 8 mg/kg IV (max 800 mg) for prolonged CRS (>3 days) or in patients with significant symptoms, comorbidities, or elderly patients 1
  • For patients treated with axicabtagene ciloleucel or brexucabtagene autoleucel, consider tocilizumab if symptoms persist >24 hours 1

• Grade 2 CRS (fever with hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen):

  • Tocilizumab 8 mg/kg IV over 1 hour (max 800 mg/dose)
  • Can repeat dose every 8 hours if no improvement
  • Maximum 3 doses in 24 hours, 4 doses total 1
  • Consider dexamethasone 10 mg IV every 12-24 hours for persistent hypotension after 1-2 doses of tocilizumab 1

• Grade 3-4 CRS:

  • Same tocilizumab dosing as Grade 2 if maximum dose not reached within 24 hours
  • Add dexamethasone 10 mg IV every 6 hours (Grade 3) or methylprednisolone (Grade 4) 1

For Rheumatoid Arthritis

• Intravenous administration: 8 mg/kg every 4 weeks 2, 3
• Subcutaneous administration: 162 mg weekly or every other week (depending on weight) 2

For Giant Cell Arteritis

• Intravenous: 6 mg/kg every 4 weeks 2
• Subcutaneous: 162 mg weekly or every other week 2

For Steroid-Refractory Acute Graft-versus-Host Disease

• 8 mg/kg IV every 2-4 weeks 1
  • More frequent dosing (every 2 weeks) appears to yield better results than every 3-4 weeks 1

Pharmacokinetic Considerations

• Half-life varies by indication and administration route:

  • RA: 11-13 days for IV administration, 5-13 days for SC administration 2
  • GCA: 13.2 days for IV, 4.2-18.9 days for SC 2
  • COVID-19: Serum concentrations below detection limit after approximately 35 days 2

• Body weight considerations:

  • Higher exposure in patients with lower body weight
  • For SC dosing in GCA patients <60 kg, steady-state concentration is 51% higher (weekly dosing) or 129% higher (every other week dosing) compared to patients 60-100 kg 2

Monitoring Requirements

• Complete blood count (CBC) and liver function tests (LFTs):
  • Within first 1-2 months of usage
  • Every 3-4 months thereafter 1
• Lipid levels: Every 6 months 1
• Dose adjustment recommendations for abnormal LFTs:
  • If 1-3 times ULN: Decrease dose or increase interval between doses
  • If >3 times ULN: Withhold administration
  • If >5 times ULN: Discontinue treatment 1

Important Safety Considerations

1. Infection risk: Monitor for signs of infection, particularly in neutropenic patients 1
2. Hematologic effects: Monitor for neutropenia, thrombocytopenia, and anemia 2, 4
3. Lipid abnormalities: Significant increases in total, HDL, LDL cholesterol, and triglycerides 4
4. Hepatotoxicity: Do not initiate in patients with elevated LFTs (>1.5 times ULN) 1
5. Rare complications: Cases of accelerated subcutaneous nodulosis have been reported 5

Special Populations

• COVID-19 patients: Under FDA Emergency Use Authorization, limit to maximum of 2 doses during a CRS episode and consider more aggressive steroid use 1
• Pediatric patients: Different dosing based on body weight categories and indication 2
• Elderly: Consider one dose for Grade 1 CRS due to comorbidities 1

Remember that tocilizumab availability may be limited due to FDA Emergency Use Authorization for COVID-19 patients, which may necessitate alternative approaches such as earlier or more aggressive steroid use or consideration of alternative agents like siltuximab or anakinra 1.