What are the contraindications to ravulizumab (Complement Component 5 inhibitor) in patients with a history of Neisseria meningitidis infection, complement system disorders, or impaired renal function?

Contraindications to Ravulizumab

The only absolute contraindication to ravulizumab is an unresolved serious Neisseria meningitidis infection. 1

Absolute Contraindication

• Active meningococcal infection: Initiation of ravulizumab treatment is contraindicated in patients with unresolved serious Neisseria meningitidis infection (septicemia and/or meningitis). 1

Critical Pre-Treatment Requirements (Not Contraindications, But Mandatory)

While not absolute contraindications, the following conditions require specific management before ravulizumab can be safely initiated:

Meningococcal Vaccination Status

• Unvaccinated patients requiring urgent therapy: If urgent ravulizumab therapy is indicated in a patient who is not up-to-date with meningococcal vaccines, the drug can still be administered, but antibacterial prophylaxis must be provided simultaneously and meningococcal vaccines administered as soon as possible. 1

• Vaccination requirements: Complete or update meningococcal vaccination for serogroups A, C, W, Y, and B at least 2 weeks prior to the first dose of ravulizumab, according to current ACIP recommendations for patients receiving complement inhibitors. 1

• High-risk populations: Patients with anatomical or functional asplenia (including sickle cell disease), persistent complement component deficiency, or HIV infection require a 2-dose series of MenACWY at least 8 weeks apart, plus either a 2-dose series of MenB-4C at least 1 month apart or a 3-dose series of MenB-FHbp. 2

Important Clinical Caveats

Vaccination does not eliminate meningococcal infection risk: Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors like ravulizumab. 1 This is supported by research showing that despite 4CMenB vaccination, PNH patients on eculizumab (a similar C5 inhibitor) had impaired killing of Neisseria meningitidis serogroup B in whole blood. 3

Non-capsulated strains pose additional risk: Cases of life-threatening infection by non-groupable (non-capsulated) Neisseria meningitidis have been reported in patients on ravulizumab, despite vaccination, as these strains are not covered by available vaccines. 4

Immunosuppression compounds risk: Patients transitioning from other immunosuppressive therapies (particularly rituximab) to ravulizumab face heightened infection risk, as B-cell depletion may impair vaccine response even when vaccination is completed before ravulizumab initiation. 5

Monitoring Requirements

• Continuous vigilance: Closely monitor all patients for early signs and symptoms of meningococcal infection (fever, headache, stiff neck, rash, confusion) and evaluate immediately if infection is suspected. 1

• Patient education: Inform patients of meningococcal infection signs and symptoms and instruct them to seek immediate medical care if these occur, as meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. 1

• Treatment interruption consideration: Consider interrupting ravulizumab in patients undergoing treatment for serious meningococcal infection, depending on the risks of interrupting treatment in the underlying disease being treated. 1

REMS Program Requirement

• Ravulizumab is available only through a restricted REMS program due to meningococcal infection risk, requiring prescriber enrollment, patient counseling, provision of educational materials, and assessment of vaccination status. 1