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Eculizumab
- indication:For the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
- pharmacologypharmacology:
- mechanism: A genetic mutation in PNH patients leads to the generation of populations of abnormal RBCs (known as PNH cells) that are deficient in terminal complement inhibitors (CD-59), rendering PNH RBCs sensitive to persistent terminal complement-mediated destruction. The destruction and loss of these PNH cells (intravascular hemolysis) results in low RBC counts (anemia) and also fatigue, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots. Eculizumab, the active ingredient in Soliris, is a monoclonal antibody that binds to the complement protein C5 specifically and with high affinity, thereby inhibiting its cleavage to C5a and C5b and subsequent generation of the terminal complement complex C5b-9. Soliris inhibits terminal complement mediated intravascular hemolysis in PNH patients and therefore the destruction of PNH erythrocytes that lack complement protection with CD-59.
- toxicity:
- absorprion:
- halflife: 272 ± 82 hrs (mean ± SD)
- roouteelimination:
- volumedistribution: * 7.7 L
- clearance: * 22 mL/hr [typical PNH patient weighing 70 kg]