What is the ravulizumab (Complement inhibitor) loading dose for adults and adolescents with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome (aHUS)?

Ravulizumab Loading Dose

For adults and adolescents with PNH or aHUS, ravulizumab loading dose is weight-based: 2400 mg for patients 40 to <60 kg, 2700 mg for 60 to <100 kg, and 3000 mg for ≥100 kg, administered as a single intravenous infusion. 1, 2

Weight-Based Loading Dose Regimen

The loading dose must be determined by patient body weight at treatment initiation 3:

• 40 to <60 kg: 2400 mg IV as single dose
• 60 to <100 kg: 2700 mg IV as single dose
• ≥100 kg: 3000 mg IV as single dose

1, 2, 3

Administration Details

Infusion time is significantly shorter than eculizumab, requiring approximately 2 hours for the loading dose compared to eculizumab's longer infusion duration 3. The loading dose should be administered intravenously over this timeframe 1.

Maintenance Dosing Following Loading

After the loading dose, maintenance dosing begins on day 15 and continues every 8 weeks, also weight-stratified 3:

• 40 to <60 kg: 3000 mg every 8 weeks
• 60 to <100 kg: 3300 mg every 8 weeks
• ≥100 kg: 3600 mg every 8 weeks

3, 4

Critical Pre-Treatment Requirements

Patients must receive meningococcal vaccination (serogroups A, C, W, Y and B) at least 2 weeks before initiating ravulizumab due to dramatically increased risk of meningococcal infection with complement inhibition 1, 2. If treatment cannot be delayed, administer appropriate antimicrobial prophylaxis until 2 weeks after vaccination 1.

Common Dosing Pitfalls

Real-world data from US claims analysis revealed that 59.1% of patients received above label-recommended loading doses, with mean loading dose of 3316 mg exceeding the maximum recommended 3000 mg 4. This represents inappropriate dosing that should be avoided—strictly adhere to weight-based dosing tables 4.

The mean loading dose was higher in eculizumab-naive patients (3581 mg) versus eculizumab-experienced patients (3093 mg), suggesting potential confusion during treatment transitions 4. When switching from eculizumab to ravulizumab, use the standard weight-based loading dose without adjustment for prior eculizumab exposure 4.

Treatment Context

Ravulizumab should be initiated immediately upon suspicion of aHUS without waiting for genetic test results, as genetic mutations are only identified in 50-60% of cases and delays increase morbidity and mortality 1, 2. For PNH, the extended 8-week dosing interval (versus eculizumab's 2-week interval) significantly reduces infusion center visits and improves quality of life while maintaining equivalent efficacy 3, 5.