Usage
Tocilizumab is prescribed for the treatment of moderate to severe rheumatoid arthritis in adults, polyarticular juvenile idiopathic arthritis in children aged two years and older, systemic juvenile idiopathic arthritis in children aged two years and older, giant cell arteritis in adults, cytokine release syndrome induced by chimeric antigen receptor T-cell therapy in adults and children aged two years and older, and interstitial lung disease associated with systemic sclerosis in adults. It’s classified as an immunosuppressant, specifically an interleukin-6 (IL-6) receptor antagonist. It works by blocking the activity of IL-6, a protein that plays a crucial role in inflammation.
Alternate Names
Tocilizumab is also known internationally by its brand name, Actemra.
How It Works
Pharmacodynamics: Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors. This action inhibits IL-6-mediated signaling, which leads to a reduction in the production of inflammatory cytokines and acute-phase reactants.
Pharmacokinetics: Tocilizumab exhibits linear pharmacokinetics across a wide range of doses. Subcutaneous administration has a bioavailability of approximately 80%. It is metabolized slowly, primarily through hepatic and renal pathways. Elimination is mainly through feces, with a small amount excreted in urine. The drug’s half-life ranges from 11 to 18 days.
Mode of Action: Tocilizumab’s mode of action involves competitive inhibition of IL-6 binding to its receptors. This prevents the activation of intracellular signaling pathways responsible for inflammation.
Receptor Binding: Tocilizumab specifically targets IL-6 receptors, both membrane-bound and soluble. It does not bind to other cytokine receptors.
Elimination Pathways: Tocilizumab is primarily eliminated by hepatic metabolism, with a small portion excreted unchanged in urine. A minor role is played by CYP enzymes.
Dosage
Standard Dosage
Adults:
- Rheumatoid Arthritis, Giant Cell Arteritis: 162 mg subcutaneously once a week or 8mg/kg intravenous infusion every 4 weeks, potentially increasing to 8 mg/kg based on clinical response, not exceeding 800mg per dose.
- Cytokine Release Syndrome: 8 mg/kg intravenous infusion as a single dose.
- Interstitial Lung Disease: Initial dose of 4mg/kg intravenously every 4 weeks, with potential increase to 8mg/kg, intravenously, every 4 weeks based on clinical response and not exceeding 800mg.
Children:
- Polyarticular Juvenile Idiopathic Arthritis: Children weighing 30 kg or more: 162 mg subcutaneously every two weeks. Children weighing less than 30 kg: 162 mg subcutaneously every three weeks.
- Systemic Juvenile Idiopathic Arthritis: Children weighing 30 kg or more: 162 mg subcutaneously once a week. Children weighing less than 30 kg: 162 mg subcutaneously every two weeks.
- Cytokine Release Syndrome: 8 mg/kg intravenously, as a single dose for children aged 2 and above.
Special Cases:
- Elderly Patients: No specific dose adjustment based on age. However, they might require close monitoring due to increased risk of infections.
- Patients with Renal Impairment: No dose adjustment is generally necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is generally necessary.
- Patients with Comorbid Conditions: No specific guidelines. Assess on a case-by-case basis.
Clinical Use Cases
Dosing for specific conditions as outlined in “Standard Dosage” section. No separate dosage recommendations for situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments might be required based on clinical response and tolerance. Patients with severe infections should discontinue treatment until the infection resolves.
Side Effects
Common Side Effects
Upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased cholesterol levels, injection site reactions (pain, redness, swelling).
Rare but Serious Side Effects
Serious infections (including tuberculosis and opportunistic infections), gastrointestinal perforation, anaphylaxis, severe allergic reactions, liver injury.
Long-Term Effects
Potential risk of certain cancers with prolonged use.
Adverse Drug Reactions (ADR)
Serious infections requiring hospitalization, hypersensitivity reactions.
Contraindications
Active, severe infections. Hypersensitivity to tocilizumab or any component of the formulation.
Drug Interactions
Tocilizumab interacts with several medications, including some antibiotics, antifungals, immunosuppressants, and cholesterol-lowering drugs. It can also interact with live vaccines. Consult a comprehensive drug interaction checker for detailed information. Concurrent use of live attenuated vaccines is contraindicated. The concomitant use of tocilizumab with other biologic DMARDs is not recommended.
Pregnancy and Breastfeeding
Limited data on pregnancy; use only if clearly necessary. Monitor infants exposed in utero for immune effects. It is unknown whether tocilizumab is present in human milk. However, due to its high molecular weight, it is expected that minimal amounts will be present. A decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother and the risk of potential infant side effects.
Drug Profile Summary
- Mechanism of Action: IL-6 receptor antagonist, suppressing inflammation.
- Side Effects: Infections, upper respiratory tract infections, headache, hypertension.
- Contraindications: Active, severe infections; hypersensitivity.
- Drug Interactions: Numerous drug interactions, including some antibiotics, antifungals, immunosuppressants, and live vaccines.
- Pregnancy & Breastfeeding: Use with caution; monitor infants.
- Dosage: Varies depending on condition; see dosage section.
- Monitoring Parameters: Complete blood count, liver function tests, lipid profile, signs of infection.
Popular Combinations
Methotrexate (for rheumatoid arthritis) and corticosteroids (in some specific indications and often for a limited time).
Precautions
Screen for tuberculosis and infections before initiating therapy. Monitor closely for signs of infection during and after treatment. Caution in patients with a history of diverticulitis or gastrointestinal perforation. Evaluate liver function and lipid profile regularly. The first dose of subcutaneous injection should be administered under medical supervision.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tocilizumab?
A: The dosage varies based on the indication and patient factors. Refer to the detailed dosage section above for specific recommendations for adults and children, including special considerations for different conditions.
Q2: What are the most common side effects of Tocilizumab?
A: Common side effects include upper respiratory tract infections, headache, high blood pressure, and increased cholesterol levels.
Q3: How does Tocilizumab work?
A: Tocilizumab blocks the action of interleukin-6 (IL-6), a protein that plays a key role in inflammation.
Q4: Can Tocilizumab be used during pregnancy?
A: Tocilizumab should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Consult the pregnancy section for more details.
Q5: What are the serious side effects of Tocilizumab?
A: Serious side effects can include serious infections, including tuberculosis, gastrointestinal perforation, and severe allergic reactions.
Q6: Does Tocilizumab interact with other medications?
A: Yes, Tocilizumab can interact with many medications. Consult a comprehensive drug interaction checker or the drug interaction section above for more details. Always inform your doctor about all other medicines you are taking.
Q7: How is Tocilizumab administered?
A: Tocilizumab can be administered intravenously or subcutaneously.
Q8: What should patients be monitored for while on Tocilizumab?
A: Patients on Tocilizumab should be monitored for signs of infection, liver function abnormalities, changes in blood counts, and lipid profile changes.
Q9: Is Tocilizumab a biologic drug?
A: Yes, Tocilizumab is a biologic drug, specifically a monoclonal antibody.
Q10: What are the contraindications for using Tocilizumab?
A: The main contraindications are active, severe infections, and hypersensitivity to tocilizumab or any of its components.
