Actemra

Approved Indications:

• Rheumatoid Arthritis (RA):
• Adults with moderate to severe active RA who have had an inadequate response to one or more DMARDs (including TNF antagonists).
• Systemic Juvenile Idiopathic Arthritis (sJIA):
• For children ≥2 years with active sJIA.
• Polyarticular Juvenile Idiopathic Arthritis (pJIA):
• For children ≥2 years with active pJIA.
• Cytokine Release Syndrome (CRS):
• Management of severe or life-threatening CRS induced by CAR T-cell therapy.
• Giant Cell Arteritis (GCA):
• For adults with GCA.
• COVID-19–related pneumonia:
• For hospitalized adults requiring supplemental oxygen, non-invasive or invasive ventilation, or ECMO.

Off-label / Clinically Accepted Uses:

• Adult-onset Still's disease
• Systemic Lupus Erythematosus (SLE) (refractory cases)
• Refractory Castleman disease
• Takayasu arteritis

Adults:

• Rheumatoid Arthritis:
• IV: 4 mg/kg every 4 weeks; may increase to 8 mg/kg based on response.
• SC: 162 mg once weekly or every other week depending on body weight and prior biologic use.
• GCA:
• SC: 162 mg once weekly, in combination with tapering corticosteroids.
• COVID-19:
• IV: 8 mg/kg (max 800 mg) single dose; repeat in 12–24 hours if needed (max 2 doses total).

Pediatric (≥2 years):

• sJIA:
• IV:
• <30 kg: 12 mg/kg every 2 weeks
• ≥30 kg: 8 mg/kg every 2 weeks
• pJIA:
• IV:
• <30 kg: 10 mg/kg every 4 weeks
• ≥30 kg: 8 mg/kg every 4 weeks

Special Populations:

• Renal Impairment:
• No dose adjustment required, but limited data available.
• Hepatic Impairment:
• Not recommended in moderate to severe hepatic impairment.
• Elderly:
• No adjustment needed, but increased risk of infections.
• Route of Administration:
• IV infusion over 60 minutes; SC injection (abdomen or thigh, rotating sites).

Tocilizumab is a recombinant humanized monoclonal antibody that specifically targets the interleukin-6 receptor (IL-6R), both soluble and membrane-bound forms. By binding to IL-6R, it inhibits IL-6-mediated signal transduction, which is a key driver of inflammation in autoimmune diseases such as RA and JIA. IL-6 is involved in the activation of T cells, B cells, macrophages, osteoclasts, and hepatic acute-phase response. Tocilizumab thereby reduces systemic inflammation, joint damage, and acute-phase reactants like CRP and serum amyloid A.

• Absorption:
• SC bioavailability: ~80%
• Tmax: 2–8 days after SC injection
• Distribution:
• Vd: 6.4 L for RA; linear and dose-proportional
• Metabolism:
• Catabolized into small peptides and amino acids via reticuloendothelial system
• Elimination:
• Biphasic clearance: linear and nonlinear (target-mediated)
• Half-life: 11–13 days (RA, IV dosing); prolonged at higher doses
• Steady State:
• Reached after 8–12 weeks of regular dosing

• Pregnancy:
• FDA Category: Not assigned (formerly Category C)
• Animal studies show fetal harm; human data limited. Use only if benefits outweigh potential risks.
• Consider discontinuation prior to conception if possible.
• Lactation:
• Detected in low amounts in human milk.
• Unknown effects on nursing infant; caution advised.
• Avoid breastfeeding for at least 2 weeks after last dose (manufacturer recommendation).

• Primary Class: Immunosuppressive Agent
• Subclass: Interleukin-6 (IL-6) Receptor Antagonist / Anti-rheumatic Biologic (Non-TNF)

• Known hypersensitivity to Tocilizumab or any component
• Active serious infections (e.g., TB, sepsis)
• Severe hepatic impairment (Child-Pugh C)
• Concurrent use with live vaccines

• Infections:
• Serious infections (bacterial, fungal, viral, opportunistic) may occur; test for latent TB before initiating therapy.
• Gastrointestinal Perforations:
• Especially in patients with diverticulitis; monitor abdominal symptoms.
• Hematologic Effects:
• May cause neutropenia and thrombocytopenia; monitor CBC regularly.
• Liver Toxicity:
• Elevated transaminases; discontinue if ALT/AST >5× ULN.
• Lipids:
• Increases in LDL, HDL, and triglycerides; monitor lipid panel.
• Malignancy Risk:
• Long-term immunosuppression may increase cancer risk.
• Immunizations:
• Avoid live vaccines during and immediately after treatment.

Common:

• Infections: Upper respiratory tract infections, nasopharyngitis
• GI: Nausea, diarrhea
• Dermatologic: Injection site reactions (SC)
• Hematologic: Neutropenia, thrombocytopenia
• Liver: Elevated ALT/AST
• Metabolic: Hyperlipidemia

Serious/Rare:

• Severe infections (e.g., TB, pneumonia)
• GI perforation
• Anaphylaxis or hypersensitivity reactions
• Hepatitis or liver failure
• Demyelinating disorders (rare)
• Malignancy (long-term use)

Timing/Severity:

• Neutropenia typically occurs within first 4–8 weeks
• Hepatic enzyme elevations and lipid changes are dose-dependent

• CYP450 Modulation:
• IL-6 inhibition can restore CYP450 enzyme activity, reducing serum levels of drugs metabolized by CYP3A4, CYP1A2, CYP2C9 (e.g., warfarin, cyclosporine, omeprazole, simvastatin, theophylline).
• Monitor closely if patient is stabilized on such drugs.
• Live Vaccines:
• Avoid during and after therapy due to risk of uncontrolled infection.
• Immunosuppressants:
• Additive risk of infection with concurrent biologics or high-dose corticosteroids.

• FDA and WHO Emergency Use:
• Tocilizumab granted Emergency Use Authorization (EUA) during the COVID-19 pandemic for hospitalized adults with systemic inflammation and respiratory failure.
• Labeling Updates:
• Black box warnings on serious infections and potential mortality risk from GI perforation and hepatotoxicity.
• NICE/EMA:
• Recommended in combination with corticosteroids for refractory GCA and moderate-severe RA.
• Ongoing Investigations:
• Evaluated in various cytokine-driven conditions beyond COVID-19, including HLH and multisystem inflammatory syndromes.

• IV Formulation (vials):
• Store at 2°C to 8°C (refrigerated); do not freeze
• Protect from light
• Use immediately after dilution or within 24 hours if refrigerated
• SC Prefilled Syringes/Pens:
• Store at 2°C to 8°C
• May be kept at room temperature (up to 25°C) for up to 2 weeks
• Do not shake or expose to heat or light
• Discard if frozen or expired