Makindo Medical Notes

Related Subjects: Temporal (Giant Cell GCA) Arteritis Tocilizumab

About: Always check the BNF link here

• Check BNF or equivalent for UpToDate prescribing advice

Mode of action

• A humanised antihuman IL-6 receptor antibody of the IgG1 subclass. IL-6 is important for CRP production
• Tocilizumab binds to both soluble and membrane-bound IL-6 receptors, inhibiting IL-6-mediated signaling pathways.
• By blocking IL-6, it reduces inflammation and modulates the immune response.

Indications/Dose(Specialist use only)

• Rheumatoid Arthritis: Moderate to severe cases in adults, especially those with an inadequate response to disease-modifying antirheumatic drugs (DMARDs).
• Systemic Juvenile Idiopathic Arthritis (sJIA): For the treatment of active sJIA in patients aged two years and older.
• Giant Cell Arteritis: To treat adults with active disease, including cranial manifestations.
• Cytokine Release Syndrome (CRS): For severe or life-threatening CRS associated with CAR T-cell therapy.
• COVID-19: Emergency use authorization for treating severe COVID-19 patients with systemic inflammation.

Dose range:You must check with BNF or drug datasheet

• Rheumatoid Arthritis:
  • IV infusion: 4 mg/kg every four weeks.
  • SC injection: 162 mg once weekly or every other week.
• Systemic Juvenile Idiopathic Arthritis: 8 mg/kg IV every four weeks.
• Giant Cell Arteritis: 8 mg/kg IV once, followed by maintenance doses based on clinical response. Also 162 mg once weekly SC or every other week.
• Cytokine Release Syndrome: Initial dose of 8 mg/kg IV, may repeat after 8 hours if necessary.
• COVID-19: 8 mg/kg IV once, may administer a second dose 12-24 hours later if needed.

Precautions

• Screen for latent infections, including tuberculosis, before initiating therapy.
• Monitor liver function tests regularly.
• Avoid use in patients with active infections.
• Use with caution in patients with a history of diverticulitis or gastrointestinal perforations.
• Regularly monitor blood counts to detect cytopenias.

Interactions

• Increased risk of infections when used with other immunosuppressants.
• May alter the metabolism of concomitant drugs metabolized by CYP450 enzymes.
• Avoid live vaccines during therapy.

Side effects

• Common: Upper respiratory tract infections, headache, hypertension, injection site reactions.
• Serious:
  • Infections (including opportunistic infections).
  • Liver enzyme elevations.
  • Gastrointestinal perforations.
  • Neutropenia and thrombocytopenia.
  • Hyperlipidemia.
• Other: Increased risk of malignancies, hypersensitivity reactions.

Cautions

• May have a normal CRP in presence of infection or inflammation
• Patients with latent tuberculosis should be treated with standard therapy before starting tocilizumab.
• Discontinue if absolute neutrophil count less than 0.5 x 10⁹/litre or platelet count less than 50 x 10³/microlitre.

Contraindications

• Do not initiate if absolute neutrophil count less than 2 x 10⁹/litre; severe active infection

Side effects

• Increase in serum total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides.
• Neutropenia and deranged LFTs

References

• See BNF