ACTEMRA 400MG

Indications

• Rheumatoid arthritis
• Systemic juvenile idiopathic arthritis
• Giant cell arteritis
• Chimeric antigen receptor T-cell (CAR-T) therapy-related cytokine release syndrome

Dosage

Children: For systemic juvenile idiopathic arthritis, the dose for children aged 2 years and older is 12 mg/kg every 2 weeks, with a maximum of 8 mg/kg for those weighing less than 30 kg. For children over 30 kg, the adult dosing regimen may be applied. Consult the BNF for Children for further details.

Adults: For rheumatoid arthritis, the recommended dose is 8 mg/kg every 4 weeks, with a maximum of 800 mg per dose. For other conditions, dosing may vary; refer to specific guidelines for adjustments.

Mechanism of action

Tocilizumab binds to both soluble and membrane-bound IL-6 receptors, thereby blocking the interaction between IL-6 and its receptors. This inhibition prevents the downstream signaling pathways that mediate inflammatory responses, ultimately leading to a reduction in the activity of immune cells involved in inflammation.

Pharmacodynamics

The pharmacodynamic effects of tocilizumab include a decrease in the levels of C-reactive protein (CRP), a marker of inflammation, and improvement in clinical symptoms associated with autoimmune conditions such as pain, swelling, and stiffness. The onset of action can vary, with some patients experiencing improvement within weeks, while others may take longer to respond.

Pharmacokinetics

Tocilizumab is administered via subcutaneous injection or intravenous infusion. It has a half-life of approximately 11 to 13 days, allowing for less frequent dosing. The drug is primarily metabolized by the liver, and its clearance can be affected by factors such as liver function and the presence of other medications. Dosing adjustments may be necessary for patients with liver enzyme abnormalities.

Contra-indications

• Severe active infection
• Active infection
• Neutropenia (absolute neutrophil count less than 1.5 x 10^9/litre)
• Pre-existing malignancy
• Chronic infection
• History of recurrent infection
• Inflammatory bowel disease (discontinue if signs or symptoms develop, or an exacerbation occurs)

Adverse effects

• Headache
• Fatigue
• Diarhoea
• Skin reactions
• Neutropenia (usually mild and reversible)
• Thrombocytopenia
• Anaphylactic reaction
• Hepatitis

Interactions

• Filgotinib (severe - increases risk of immunosuppression)
• Aminophylline (moderate - decreases exposure)
• Antiepileptics (moderate - decreases exposure)
• Fosphenytoin (moderate - decreases exposure)
• Phenytoin (moderate - decreases exposure)
• Benzodiazepines (moderate - decreases exposure)
• Alprazolam (moderate - decreases exposure)
• Diazepam (moderate - decreases exposure)
• Midazolam (moderate - decreases exposure)
• Calcium channel blockers (moderate - decreases exposure)

Precautions

• Monitor for new serious infection during treatment
• Consider risk of immunosuppression
• Assess liver enzyme abnormalities before use
• Use caution in patients with a history of tuberculosis, or those at risk for latent tuberculosis

Pregnancy

Manufacturer advises to avoid due to lack of information on safety.

Breast-feeding

Manufacturer advises to avoid during treatment and for up to 20 weeks after discontinuing treatment, no information available.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.

Formulations

• Solution for injection
• Pre-filled disposable injection syringes