Generic Name

Eculizumab

Mechanism

Eculizumab is a humanized monoclonal antibody that binds with high affinity to the complement protein C5.
• Inhibits cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby preventing formation of the membrane‑attack complex (MAC).
• Blocks downstream inflammatory and hemolytic pathways that drive diseases such as *paroxysmal nocturnal hemoglobinuria* (PNH), *atypical hemolytic uremic syndrome* (aHUS), and *refractory generalized myasthenia gravis*.
• Reversible and requires repeated dosing to sustain therapeutic complement blockade.

Pharmacokinetics

• Absorption: Intravenous (IV) infusion; rapid achievement of therapeutic serum concentrations.
• Distribution: Volume of distribution ≈ 6–10 L; predominantly extracellular and bound to soluble CD59.
• Metabolism: Cleared primarily by proteolytic catabolism; not significantly metabolized by CYP enzymes.
• Elimination: T½ ≈ 26 days; steady‑state achieved after ~4–5 infusions.
• Special Populations: No dosage adjustment for age, sex, or mild–moderate renal/hepatic impairment; caution in severe renal dysfunction.

Indications

• Paroxysmal nocturnal hemoglobinuria (PNH) – all disease severities.
• Atypical hemolytic uremic syndrome (aHUS) – complement‑mediated forms.
• Refractory generalized myasthenia gravis – as adjunct therapy.
• Other investigational uses: Lupus nephritis, anti‑glomerular basement‑membrane disease, and some complement‑driven ocular disorders.

Contraindications

• Active meningococcal infection – contraindicated.
• Severe uncontrolled infection – defer until infection resolves.
• Pregnancy & lactation – limited data; risk–benefit assessment required.
• Vaccination status: Vaccinate against *Neisseria meningitidis* at least 2 weeks before first dose; repeat boosters per schedule.

Dosing

• Initial therapy:
• 300 mg IV infusion (1 h) on days 0, 7, 14, 21, 28.
• Subsequent doses 300 mg IV every 2 weeks.
• Maintenance in PNH: 300 mg IV bi‑weekly, may reduce to 600 mg every 4 weeks after 6–12 months of stable response.
• Maintenance in aHUS: 300 mg IV every 2 weeks or 600 mg every 4 weeks, depending on serum C5 activity.
• Infusion considerations: Premedicate with antihistamine if infusion reaction suspected; monitor during first 2 h.

Adverse Effects

• Common:
• Injection‑site reaction, headache, nasopharyngitis, chills.
• Mild fever or transient hypotension.
• Serious:
• Meningococcal septicemia (peak 3–7 days post‑infusion).
• Opportunistic infections: *Pneumocystis jirovecii*, *Candida*, *Herpes simplex*.
• Hypersensitivity reactions, anaphylaxis.
• Hematologic: neutropenia, thrombocytopenia (rare).
• Cytopenias linked to other drug interactions.

Monitoring

• Infection surveillance:
• Review for signs of meningococcal illness; report rapidly.
• Monitor CBC, CMP, and urinalysis monthly.
• Complement activity:
• Serum C5 and complement levels (CH50) at baseline, 2 weeks post‑initiation, and every 3 months.
• Renal function:
• eGFR or creatinine for aHUS patients.
• Vaccination coverage: Verify meningococcal vaccine titers; consider booster if >6 months.

Clinical Pearls

• Rapid init dose: 300 mg IV every *2 weeks* is the “gold‑standard” for initial and maintenance therapy; skipping doses can precipitate breakthrough hemolysis.
• Pregnancy counseling: While data are scarce, the benefit of continuing therapy often outweighs potential risks; involve obstetric specialists.
• Infections: Check for any febrile illness before infusion; adequate hydration and analgesics can mitigate post‑infusion “cytokine‑like” symptoms.
• Dose adjustment: In patients with low complement activity (< 5 % residual activity), switch to the higher 600 mg every 4‑week schedule to avoid complement rebound.
• Home infusion feasibility: Many patients transition to home IV infusions after 4 months; requires trained phlebotomy or nurse‑led services.
• Immunogenicity: Treatment‑induced anti‑eculizumab antibodies are rare but may reduce efficacy; consider alternative complement inhibitors if refractory.

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