|
| Primary information |
|---|
| ID | 10497 |
| Therapeutic ID | Th1093 |
| Protein Name | Eculizumab |
| Sequence | NA
|
| Molecular Weight | 148000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 272 ± 82 hrs (mean ± SD) |
| Description | Soliris is a formulation of eculizumab which is a recombinant humanized monoclonal IgG2/4;K antibody. Recombinant; produced in murine myeloma cell culture. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions and has a molecular weight of approximately 148 kDa. |
| Indication/Disease | For the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. |
| Pharmacodynamics | Eculizumab is a monoclonal antibody directed against the complement protein C5. This antibody blocks the cleavage of C5 and halts the process of complement-mediated cell destruction. Eculizumab is a product of Alexion Pharmaceuticals and has been shown to be effective in treating paroxysmal nocturnal hemoglobinuria. Eculizumab was approved by the FDA in March, 2007. |
| Mechanism of Action | 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 | Overdoses of eculizumab are unlikely as it is administered under specialist supervision.8 In case of overdose, contact local poison control |
| Metabolism | Eculizumab is a monoclonal antibody and is expected to be metabolized to small peptides and amino acids. |
| Absorption | Eculizumab is administered by intravenous infusion so the bioavailability is 100%.7 This drug reaches a Cmax of 194±76µg/mL and Ctrough of 97±60µg/mL.7 The AUC was calculated to be 24,467.6µg*h/mL |
| The volume of distribution of eculizumab is 5-8L |
| Clearance | Pharmacokinetic properties in healthy patients have not been determined.4 In patients with rhematoid arthritis, there is an average clearance of 0.26mL/kg/h. |
| Categories | NA |
| Patents Number | CA2189015 |
| Date of Issue | 13-Apr-2010 |
| Date of Expiry | 1-May-2015 |
| Drug Interaction | NA |
| Target | Complement C5 |
| Brand Name | Soliris |
| Company | Alexion, Inc |
| Brand Description | Alexion, Inc |
| Prescribed For | indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis |
| Chemical Name | NA |
| Formulation | The product is formulated at pH 7 and each vial contains 300 mg of eculizumab, 13.8 mg sodium phosphate monobasic, 53.4 mg sodium phosphate dibasic, 263.1 mg sodium chloride, 6.6 mg polysorbate 80 (vegetable origin) and Water for Injection, USP. |
| Physical Appearance | Sterile, clear, colorless, preservative-free 10 mg/mL solution for Intravenous infusion and is supplied in 30-mL single-use vials |
| Route of Administration | NA |
| Recommended Dosage | 600 mg weekly for the first 4 weeks, followed by 900 mg for the fifth dose 1 week later, then 900 mg every 2 weeks thereafter. |
| Contraindication | NA |
| Side Effects | Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |