Eculizumab

Eculizumab is a humanised monoclonal antibody against complement protein C5, given intravenously every 2 weeks, used in paroxysmal nocturnal haemoglobinuria, atypical haemolytic uraemic syndrome, generalised myasthenia gravis with antibodies to acetylcholine receptor, and neuromyelitis optica spectrum disorder with antibodies to aquaporin 4. The principal hazard is life-threatening meningococcal infection, so vaccination and antibiotic cover are mandatory. Biosimilar versions are used and are not distinguished here.

Class. Complement C5 inhibitor monoclonal antibody.

Mechanism. It binds C5 and blocks its cleavage to C5a and C5b, preventing terminal complement complex (membrane attack complex) formation, which stops intravascular haemolysis and complement-mediated endothelial injury.

Pharmacokinetics. Intravenous only, half-life about 11 to 12 days, steady state by 4 weeks. Clearance is increased by plasma exchange, plasma infusion and neonatal Fc receptor blockers, so supplemental doses are needed.

Paroxysmal nocturnal haemoglobinuria.

• Induction: 600 mg intravenously weekly for 4 weeks.

• Week 5: 900 mg.

• Maintenance: 900 mg every 2 weeks.

Atypical haemolytic uraemic syndrome, generalised myasthenia gravis and neuromyelitis optica spectrum disorder (adults).

• Induction: 900 mg intravenously weekly for 4 weeks.

• Week 5: 1200 mg.

• Maintenance: 1200 mg every 2 weeks.

Paediatric atypical haemolytic uraemic syndrome (by weight).

• 40 kg and over: adult regimen.

• 30 to under 40 kg: 600 mg weekly for 2 doses, 900 mg at week 3, then 900 mg every 2 weeks.

• 20 to under 30 kg: 600 mg weekly for 2 doses, 600 mg at week 3, then 600 mg every 2 weeks.

• 10 to under 20 kg: 600 mg once, 300 mg at week 2, then 300 mg every 2 weeks.

• 5 to under 10 kg: 300 mg once, then 300 mg every 3 weeks.

Supplemental doses. After plasma exchange: 600 mg if the most recent dose was 600 mg, or 300 mg if it was 900 mg or more, given within 60 minutes of the end of exchange. After plasma infusion: 300 mg before the infusion. A supplemental dose is also needed with neonatal Fc receptor blocker therapy.

Maximum dose. 1200 mg for each infusion in the labelled regimens.

Mandatory preparation.

• Meningococcal vaccines (conjugate ACWY and serogroup B) at least 2 weeks before the first dose, with pneumococcal and Haemophilus influenzae type b vaccines. If treatment cannot be delayed, give antibiotic prophylaxis alongside vaccination.

• Antibiotic prophylaxis (for example penicillin V 500 mg twice daily; macrolide if allergic) for the duration of treatment and for 8 weeks after the last dose.

Contraindications. Unresolved serious Neisseria meningitidis infection, and patients not currently vaccinated against Neisseria meningitidis (unless prophylaxis is given in the urgent situation). Hypersensitivity.

Boxed-warning-level risks. Life-threatening and fatal meningococcal infections (and other encapsulated bacteria). Prescribing is restricted to registered programmes in some regions.

Adverse effects. Common: headache, nasopharyngitis, back pain, nausea, infusion reactions, hypertension. Serious: meningococcal and other encapsulated bacterial infection (Streptococcus pneumoniae, Haemophilus influenzae), Aspergillus infection, thrombotic microangiopathy or haemolysis on stopping, infusion reactions, immunogenicity.

Major interactions. Neonatal Fc receptor blockers and plasma exchange (reduce levels; give supplemental doses), live vaccines (avoid), and other immunosuppressants add to infection risk.

Common prescribing errors. Starting without meningococcal vaccination or prophylaxis; omitting supplemental doses after plasma exchange; stopping abruptly in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome; missing infection symptoms.

Special groups.

• Pregnancy: limited data; continue where the benefit outweighs risk, and watch haemolysis markers closely because clearance changes.

• Breastfeeding: limited data; likely low transfer into milk.

• Children: weight-based for atypical haemolytic uraemic syndrome as stated.

• Older adults: no adjustment.

• Kidney impairment: no adjustment; used in atypical haemolytic uraemic syndrome.

• Liver impairment: no adjustment expected.

• Region: meningococcal vaccine availability and cost limit use in East Africa, and meningococcal outbreaks are reported in parts of Africa; confirm vaccine supply and prophylaxis adherence before starting. Give every patient an alert card with instructions to seek urgent care for fever, headache with stiff neck or confusion.

Formulations. 300 mg/30 mL vials. Dilute to 5 mg/mL in 0.9 percent sodium chloride or 5 percent glucose and infuse over 35 minutes (25 to 45 minutes). Observe for at least 1 hour after the infusion. Store at 2 to 8 degrees Celsius.

Baseline. Meningococcal and pneumococcal vaccination status, full blood count, lactate dehydrogenase, haptoglobin, creatinine, urinalysis, hepatitis B and C and HIV serology, and a review of infection risk.

Monitoring. Haemolysis markers (lactate dehydrogenase, haemoglobin) in paroxysmal nocturnal haemoglobinuria before each infusion; creatinine, platelets and lactate dehydrogenase in atypical haemolytic uraemic syndrome; antibiotic prophylaxis adherence; infection symptoms at each visit.

After stopping. Monitor for at least 8 weeks (paroxysmal nocturnal haemoglobinuria) or at least 12 weeks (atypical haemolytic uraemic syndrome) for haemolysis or thrombotic microangiopathy.

Stop or hold thresholds. Active meningococcal infection or other serious encapsulated infection (treat urgently), anaphylaxis, or no clinical benefit.

Referral and escalation. Specialist initiated. Fever in any patient on treatment is an emergency: urgent assessment and empirical intravenous antibiotics such as ceftriaxone 2 g every 12 hours for suspected meningococcal disease, without waiting for results.