Switching from Eculizumab to Ravulizumab After Two Doses
Administer a weight-based loading dose of ravulizumab 2 weeks after the last eculizumab dose, then continue with weight-based maintenance dosing every 8 weeks thereafter.
Dosing Algorithm for Adults
The transition from eculizumab (Soliris) to ravulizumab (Ultomiris) follows a straightforward weight-based protocol 1:
Loading Dose (Day 1)
- ≥40 kg to <60 kg: 2400 mg IV
- ≥60 kg to <100 kg: 2700 mg IV
- ≥100 kg: 3000 mg IV 1
Maintenance Dosing (Starting Day 15)
- ≥40 kg to <60 kg: 3000 mg IV every 8 weeks
- ≥60 kg to <100 kg: 3300 mg IV every 8 weeks
- ≥100 kg: 3600 mg IV every 8 weeks 1
Timing of the Switch
Give the ravulizumab loading dose 2 weeks after the last eculizumab dose 1. This timing ensures continuous C5 inhibition without gaps in complement blockade, which is critical to prevent breakthrough hemolysis or thrombotic microangiopathy 1, 2.
Evidence Supporting Direct Switching
The phase 3 trial (Study 302) specifically evaluated patients switching from stable eculizumab therapy (900 mg every 2 weeks) directly to ravulizumab 1. In this study of 195 patients:
- 95 patients switched from eculizumab to ravulizumab using the protocol above 1
- Ravulizumab demonstrated non-inferiority to continued eculizumab for all efficacy endpoints (P<0.0006) 1
- No breakthrough hemolysis occurred when serum free C5 was maintained <0.5 μg/mL 2
- All patients maintained complete C5 blockade throughout the 52-week follow-up period 2
The switch was safe and effective regardless of prior eculizumab duration, with stable lactate dehydrogenase levels, transfusion avoidance rates of 83-86%, and no meningococcal infections 2.
Critical Safety Considerations
Meningococcal Vaccination Status
Both eculizumab and ravulizumab carry identical meningococcal infection risks 3. Verify that meningococcal vaccination was completed at least 2 weeks before the first eculizumab dose 3. If not previously vaccinated:
- Do not delay the ravulizumab switch if the patient is already on eculizumab, as they are already at risk 3
- Administer MenACWY and MenB vaccines immediately if not previously given 3
- Consider antibiotic prophylaxis until 2 weeks post-vaccination 3
Monitoring During Transition
- Measure serum free C5 levels to confirm complete complement blockade (<0.5 μg/mL) 2
- Monitor for signs of breakthrough hemolysis: dark urine, fatigue, dyspnea, abdominal pain 1
- Check lactate dehydrogenase, hemoglobin, and platelet counts at weeks 2,4, and 8 after the switch 1
Common Pitfalls to Avoid
Do not use eculizumab dosing intervals for ravulizumab. The every-8-week maintenance schedule for ravulizumab is based on its 4-fold longer half-life compared to eculizumab 4, 5. Attempting to dose ravulizumab every 2 weeks (like eculizumab) provides no additional benefit and wastes resources 5.
Do not skip the loading dose. The higher loading dose (compared to maintenance) is required to achieve immediate complete C5 blockade when transitioning from eculizumab 1.
Do not delay the Day 15 maintenance dose. The first maintenance dose must be given exactly 2 weeks after the loading dose to maintain therapeutic drug levels 1.
Expected Outcomes
Patients switching from eculizumab to ravulizumab should expect:
- Equivalent disease control with non-inferior efficacy across all hematologic parameters 1
- Reduced treatment burden: 6 infusions per year instead of 26 5
- Stable or improved quality of life with maintained FACIT-Fatigue scores 2
- Similar adverse event profile: headache (27% ravulizumab vs 17% eculizumab) being most common 1