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| Primary information |
|---|
| ID | 10471 |
| Therapeutic ID | Th1085 |
| Protein Name | Agalsidase beta |
| Sequence | >Th1085_Agalsidase_beta
LDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL
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| Molecular Weight | 45351.6 |
| Chemical Formula | C2029H3080N544O587S27 |
| Isoelectric Point | 5.17 |
| Hydrophobicity | -0.307 |
| Melting point | NA |
| Half-life | 67 ± 12 min for a 1 mg/kg dose (mean infusion length = 115 minutes.) |
| Description | Recombinant human alpha-galactosidase-A produced in CHO cells. The mature protein comprises 2 subunits of 398 residues. |
| Indication/Disease | For treatment of Fabry's disease (alpha-galactosidase A deficiency) |
| Pharmacodynamics | Used in the treatment of Fabry disease, an X-linked genetic disorder of glycosphingolipid metabolism. The disease is characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, which leads to progressive accumulation of glycosphingolipids, predominantly GL-3, in many body tissues. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular accidents. Fabrazyme is intended to provide an exogenous source of alpha-galactosidase A and to limit the accumulation of these glycolipids in the tissues. Studies show unconclusive evidence for the clinical efficacy of either agalasidase alfa or agalasidase beta in preventing morbidity. |
| Mechanism of Action | Alpha-galactosidase A catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other a-galactyl-terminated neutral glycosphingolipids, such as galabiosylceramide and blood group B substances to ceramide dihexoside and galactose. |
| Toxicity | Data regarding overdoses of agalsidase beta are not readily available.6 Patients experiencing an overdose of agalsidase beta may experience an increased incidence and severity of adverse effects.6 Overdose can be managed through the use of symptomatic and supportive measures. |
| Metabolism | Data regarding the metabolism of agalsidase beta is not readily available.6 However, protein drugs are expected to be degraded by proteases and other catalytic enzymes to smaller peptides and amino acids. |
| Absorption | A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes reaches a Cmax 5.0 ± 1.1 µg/mL with an AUC of 496 ± 137 µg*min/mL |
| A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes has a VSS of 112 ± 13 mL/kg |
| Clearance | A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes has a clearance of 2.1 ± 0.7 mL/min/kg |
| Categories | Alimentary Tract and Metabolism,Amino Acids, Peptides, and Proteins,Enzymes,Enzymes and Coenzymes,Galactosidases,Glycoside Hydrolases,Hydrolases,Hydrolytic Lysosomal Neutral Glycosphingolipid-specific Enzyme,Protein Isoforms,Proteins |
| Patents Number | CA2265464 |
| Date of Issue | 26-Jun-2007 |
| Date of Expiry | 12-Sep-2017 |
| Drug Interaction | NA |
| Target | Globotriaosylceramide |
| Brand Name | Fabrazyme |
| Company | Genzyme Corp |
| Brand Description | Genzyme Corp |
| Prescribed For | Routine prophylaxis to prevent or reduce the frequency of bleeding episodes. |
| Chemical Name | NA |
| Formulation | Each 5 mg vial contains 5.5 mg of agalsidase beta as well as 33.0 mg mannitol, 3.0 mg sodium phosphate monobasic monohydrate, and 8.8 mg sodium phosphate dibasic heptahydrate. Following reconstitution as directed, 5 mg of agalsidase beta (1 mL) may be extracted from each 5 mg vial. |
| Physical Appearance | Sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with Sterile Water for Injection, uSp. Each 35 mg vial contains 37 mg of agalsidase beta as well as 222 mg mannitol, 20.4 mg sodium phosphate monobasic monohydrate, and 59.2 mg sodium phosphate dibasic heptahydr |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. |
| Side Effects | difficulty breathing; closing of the throat; hives; rash; itching; fever; shaking; chest tightness; high or low blood pressure; fast heartbeats; muscle pain; stomach pain; nausea or vomiting; dizziness; numbness or tingling; and headache have occurred upon injection of agalsidase beta in many patients. Most patients treated with agalsidase beta develop antibodies to agalsidase beta and many will develop symptoms of an infusion reaction. A slow rate of injection of the medication and pretreatment with other medications may decrease. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |