Eculizumab is an intravenous monoclonal antibody that binds to C5 and prevents formation of the membrane attack complex improving anemia, reducing thrombosis risk, improving quality of life, and improve survival age match controls.
A humanized monoclonal antibody that targets and prevents cleavage of terminal complement protein C5.
C5 is first protein of terminal complement assembly and is the juncture where complement activation pathways converge.
It inhibits the terminal complement proteins C5 and prevented cleavage into C5a, which is pro inflammatory, and C5b, which coordinates the formation of membrane attack complex.
By inhibiting C5 cleavage serum hemolysis in PNH is inhibited.
Eculizumab is a monoclonal antibody to C5 that blocks the generation of C5a and C5-9, complement activation fragments with proinflammatory and cytotoxic effects.
Also approved for the treatment of complement mediated HUS.
Eculizumab reduces hemolysis, stabilizes hemoglobin levels, reduces transfusion requirements, and improves quality of life in patients with PNH.
Eculizumab protects against complications of hemolysis such as impaired renal function, pulmonary HT, and thromboembolism.
Earlier complement components that clear microorganisms and immune complexes are not inactivated by this drug.
600 mg IV infusion over 30 minutes every 7 days for 4 weeks, followed by 900 mg for the fifth dose and then 900 mg every 2 weeks.
Can increase the risk of meningococcal infection, therefore all patients should receive vaccination 2 weeks prior to drug administration.
Associated with 1-2000 fold risk of meningococcal disease.
In a study of 79 consecutive PNH patients treated with this agent survival was not different from age and sex matched normal controls, and was significantly better than 30 patients managed before this agent (Kelly RJ et al).
Patients with C5 variants with mutations at Arg885, do not undergo blockade with eculizumab and have poor responses to this agent (Nishimura J et al).
Indicated for the treatment of atypical hemolytic uremic syndrome to inhibit complement mediated thrombotic microangiopathy.
Use contraindicated in patients with unresolved serious Neisseria meningitidis infection.
Life-threatening and fatal meningococcal infections have occurred in patients treated with eculizumab.
Most frequent adverse reactions are headache, nasopharyngitis, back pain, and nausea in PNH trials.
Most frequent adverse reactions in atypical hemolytic uremic syndrome are headaches, diarrhea, hypertension, upper respiratory infections, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, UTI, and pyrexia.
Recommended dosage are intravenous 600 mg weekly doses of the first four weeks followed by 900 mg for the fifth dose one week later, then 900 mg every two weeks thereafter for PNH.
Recommended dosage for atypical hemolytic uremic syndrome is 900 mg weekly for the first four weeks, followed by 1200 mg for the fifth dose one week later, then 1200 mg every two weeks intravenously thereafter.
Recipients have a 1,000 to 2,000-fold greater risk of invasive meningococcal disease compared to the general U.S. population.
Recommended that meningococcal vaccination be administered for all patients receiving eculizumab.
Some patients receiving eculizumab who were vaccinated with the recommended meningococcal vaccines still developed meningococcal disease, most often from nongroupable Neisseria meningitidis, which rarely causes invasive disease in healthy individuals.
The most commonly prescribed for treatment of 2 rare blood disorders: atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH).
Meningococcal conjugate (MenACWY) vaccine targets serogroups A, C, W, and Y, and provides no protection against nongroupable N. meningitidis.
Antimicrobial prophylaxis for the duration of eculizumab therapy to potentially reduce the risk of meningococcal disease.
Should continue meningococcal vaccination of all patients receiving eculizumab.
Should administer meningococcal vaccines at least 2 weeks prior to administering the first dose of eculizumab.
Need to maintain a high index of suspicion for meningococcal disease in patients taking eculizumab who present with any symptoms consistent with either meningitis or meningococcemia, even if the patient’s symptoms initially appear mild, and irrespective of the patient’s meningococcal vaccine or antimicrobial prophylaxis status.
Among patients with AQP4-IgG positive neuromyelitis optica spectrum disorder, received eculizumab had a significantly lower risk of relapse in those who received placebo.