ravulizumab
ravulizumab
Generic Name
ravulizumab
Mechanism
* Targets C5 – binds to the C5 protein before cleavage into C5a and C5b.
* Prevents assembly of the terminal membrane attack complex (MAC, C5b‑9).
* Results in decreased intravascular hemolysis and inflammation associated with uncontrolled complement activation.
Pharmacokinetics
| Parameter | Typical Value | Notes |
| Half‑life | 22–25 days | Enables 8‑week dosing interval. |
| Volume of distribution | ~4 L | Reflects plasma‑restricted distribution. |
| Clearance | ~0.033 L/h | Linear, dose‑proportional. |
| Route | Intravenous infusion | 2–3 h infusion time, pre‑infusion anti‑hypersensitivity medications often used. |
| Bioavailability | •100 % (IV) | No oral formulation. |
| Metabolism | Proteolytic catabolism | No known CYP interactions. |
Indications
* Paroxysmal nocturnal hemoglobinuria (PNH) – treatment and prevention of hemolysis.
* Atypical hemolytic uremic syndrome (aHUS) – management of complement‑driven thrombotic microangiopathy.
* Extended‑interval therapy in PNH – approved for 8‑week dosing, reducing infusion frequency versus eculizumab.
Contraindications
* Severe active infection – particularly meningococcal disease.
* Known hypersensitivity to ravulizumab or any excipients.
* Active systemic bacterial infections (pre‑infusion screening mandatory).
* Pregnancy/Lactation – not recommended unless benefits outweigh risks; limited data.
Warnings
* Neisseria meningitidis risk – patients require meningococcal vaccination ≥1 month before initiation; consider prophylactic antibiotics if vaccination incomplete.
* Immunosuppression – patients may have increased susceptibility to encapsulated bacteria.
* Interruption of therapy – can precipitate hemolytic crisis or thrombotic events; maintain infusion schedule.
Dosing
| Condition | Loading Dose | Maintenance Dose | Frequency |
| PNH | 600 mg IV (2 × 300 mg) | 600 mg IV | Every 8 weeks |
| aHUS | 600 mg IV (2 × 300 mg) | 600 mg IV | Every 8 weeks |
| PK/PD | - | 600 mg IV | - |
*Infusion time*: 2–3 h.
*Premedication*: antihistamine, acetaminophen, or corticosteroid per institutional protocol.
*Rescue medications* for infusion reactions: epinephrine, vasopressors, or bronchodilators as indicated.
Adverse Effects
Common (>5 %)
* Headache
* Nasopharyngitis
* Anemia (often related to disease)**
* Infusion‑related reactions (rash, pruritus, hypotension)
Serious (>1 %)
* Meningococcal infections – fatal if untreated.
* Serious bacterial infections (Streptococci, Klebsiella).
* Hypersensitivity reactions (anaphylaxis).
* Cytopenias (neutropenia, thrombocytopenia).
Monitoring
* Hemoglobin, LDH, haptoglobin – every 4–6 weeks (PNH).
* Renal function (creatinine, eGFR) – baseline and every 8 weeks (aHUS).
* Platelet count – quarterly.
* Vaccination status – record meningococcal, pneumococcal, Hib, and influenza.
* Serologic markers – complement activity (CH50) may be monitored in research settings.
* Infusion reaction logs – document any adverse events per infusion.
Clinical Pearls
* Extended‑interval advantage – 8‑week schedule improves adherence and reduces infusion‑center visits, but requires strict monitoring to avoid relapse.
* Vaccination timing – administer meningococcal vaccine ≥4 weeks before first dose; if late, provide prophylactic antibiotics and vaccinate post‑infusion.
* Rescue therapeutic options – eculizumab can be used if ravulizumab is unavailable or during clinical transition.
* Special populations – data support use in adults and children ≥12 kg; limited evidence for patients <12 kg or pregnant individuals.
* Infection prophylaxis – consider continuous antibiotic prophylaxis (e.g., amoxicillin) for high‑risk patients (e.g., pending vaccination).
* Renal transplant patients – ravulizumab may reduce complement‑mediated rejection; however, concomitant immunosuppression requires careful coordination.
*Tele‑pharmacy* and pharmacist‑led education can help maintain continuity during the long dosing intervals.