How should eculizumab be prescribed, including approved indications, dosing regimens, required meningococcal vaccination or prophylaxis, monitoring parameters, safety considerations, and alternative options?

Eculizumab Prescribing Guide

Critical Pre-Treatment Requirement: Meningococcal Vaccination

All patients must receive meningococcal vaccination at least 2 weeks before initiating eculizumab, or if treatment cannot be delayed, start immediate antimicrobial prophylaxis and continue throughout therapy. 1, 2, 3

Required Vaccines

• Quadrivalent meningococcal conjugate vaccine (MenACWY) covering serogroups A, C, W, Y 4, 2
• Meningococcal serogroup B vaccine (either Bexsero [MenB-4C] or Trumenba [MenB-FHbp]) 4, 2
• Both vaccines are mandatory for patients ≥10 years old receiving eculizumab 4

Antimicrobial Prophylaxis

• If vaccination cannot be completed 2 weeks before treatment: Start penicillin or macrolides (e.g., ciprofloxacin) immediately 1, 2
• Continue prophylaxis throughout entire eculizumab treatment duration 1, 2
• This is essential because eculizumab increases meningococcal infection risk approximately 2,000-fold 5

Critical Caveat on Vaccination Efficacy

• Vaccination may provide incomplete protection in patients with active disease—one study showed only 20% of aHUS patients achieved full immune response after first vaccination 6
• Eculizumab blocks C5a release, which impairs opsonophagocytic killing even in vaccinated individuals 7
• Therefore, maintain high clinical suspicion for meningococcal infection despite vaccination 2, 6

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Approved Indications

Eculizumab is FDA-approved for: 3

• Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Atypical Hemolytic Uremic Syndrome (aHUS)
• Generalized Myasthenia Gravis (gMG)
• Neuromyelitis Optica Spectrum Disorder (NMOSD)

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Standard Dosing Regimens

For PNH and aHUS

Induction Phase: 1, 2, 3

• 900 mg IV weekly for 4 consecutive weeks (weeks 1-4)
• 1,200 mg IV at week 5

Maintenance Phase: 1, 2, 3

• 1,200 mg IV every 2 weeks thereafter

For gMG and NMOSD

• Follow same dosing schedule as above 3

Dose Adjustments for Plasmapheresis/Plasma Exchange

• Supplemental doses required if patient undergoes plasmapheresis, plasma exchange, or fresh frozen plasma infusion during treatment 3
• Do not perform plasma exchange once eculizumab is started unless specifically treating TTP (ADAMTS13 <5%) 8

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Treatment Duration Considerations

For aHUS Specifically

• Minimum treatment duration: 6 months before considering discontinuation 1
• Discontinue only after minimum 3 months of stabilized/normalized renal function 1
• Risk of relapse after discontinuation is 10-20%, potentially leading to aHUS recurrence and renal failure 1

For PNH

• Treatment is typically lifelong as discontinuation leads to return of hemolysis 9

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Monitoring Parameters

Pre-Treatment Assessment

• Complete blood count with peripheral smear looking for schistocytes >1% and thrombocytopenia 8
• Hemolysis markers: LDH, haptoglobin, indirect bilirubin, reticulocyte count 1, 8
• Renal function: Serum creatinine, urinalysis for hematuria/proteinuria 8
• ADAMTS13 activity to distinguish from TTP (>5% indicates aHUS) 8
• Complement testing: C3, C4, CH50 8

During Treatment

• First week: Daily CBC, LDH, and creatinine 8
• Ongoing: Monitor hemoglobin and reticulocyte count to assess treatment response 1
• Surveillance for breakthrough hemolysis: Dark urine, fatigue, abdominal pain 1
• LDH levels should decrease within first week, reaching near-normal by week 2 9

Infection Monitoring

• Continuously monitor for meningococcal infection signs: Fever, headache, neck stiffness, confusion, flu-like symptoms 2
• Evaluate and treat immediately with antibiotics if any signs develop 2

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Critical Safety Considerations

Meningococcal Infection Risk

• This is the most serious risk with eculizumab therapy 3, 9
• Patients must carry a safety card and be educated about infection symptoms 3
• Never delay vaccination—this is the most critical safety measure 2

Special Population: East Asian Ancestry

• Screen for Chinese/Japanese ancestry before initiating therapy 1
• Polymorphic variants of the C5 gene in these populations may confer resistance to eculizumab 1
• Consider alternative therapies if genetic resistance is suspected 1

Other Infections

• Increased risk of infections with encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae) 3
• Ensure pneumococcal and Haemophilus vaccines are up to date 3

Infusion-Related Reactions

• Monitor during infusion for hypersensitivity reactions 3
• Most common adverse effects: Headache, nasopharyngitis, back pain, nausea 10, 9

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Transfusion Management During Therapy

Red Blood Cell Transfusions

• Administer only to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients 2
• Use extended antigen-matched red cells (C/c, E/e, K, Jk^a^/Jk^b^, Fy^a^/Fy^b^, S/s) when feasible 2

Platelet Transfusions

• Avoid unless life-threatening bleeding as they may worsen thrombotic complications 8

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Emergency Initiation Without Hematologist

When Immediate Treatment is Needed

• Initiate eculizumab within 4-8 hours of diagnosis in severe aHUS/TMA, even without hematologist present 8
• Establish immediate telephone or telemedicine consultation with hematologist at referral center 8
• Administer meningococcal vaccines and start antimicrobial prophylaxis immediately 8

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Common Pitfalls to Avoid

1. Never delay meningococcal vaccination—failure to vaccinate is the most dangerous error 2
2. Do not discontinue eculizumab prematurely (before 6 months minimum) in aHUS patients 1
3. Do not assume vaccination provides complete protection—maintain antimicrobial prophylaxis and high clinical suspicion 6, 7
4. Do not forget to screen for East Asian ancestry before starting therapy 1
5. Do not perform plasma exchange once eculizumab is started (except for TTP) 8
6. Never delay treatment waiting for genetic testing results in suspected aHUS 8

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Alternative Options

For PNH and aHUS

• Ravulizumab (longer-acting C5 inhibitor, dosed every 8 weeks) is an alternative to eculizumab 1
• Alternative pathway-specific inhibitors (e.g., ACH-4471/danicopan) may provide better protection against meningococcal disease as they preserve C5a-mediated opsonophagocytosis 7

For Patients with Genetic Resistance

• Consider alternative complement inhibitors or supportive care for patients of East Asian descent with C5 polymorphisms 1