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| Primary information |
|---|
| ID | 10502 |
| Therapeutic ID | Th1096 |
| Protein Name | Idursulfase |
| Sequence | >Th1096_Idursulfase
SETQANSTTDALNVLLIIVDDLRPSLGCYGDKLVRSPNIDQLASHSLLFQNAFAQQAVCAPSRVSFLTGRRPDTTRLYDFNSYWRVHAGNFSTIPQYFKENGYVTMSVGKVFHPGISSNHTDDSPYSWSFPPYHPSSEKYENTKTCRGPDGELHANLLCPVDVLDVPEGTLPDKQSTEQAIQLLEKMKTSASPFFLAVGYHKPHIPFRYPKEFQKLYPLENITLAPDPEVPDGLPPVAYNPWMDIRQREDVQALNISVPYGPIPVDFQRKIRQSYFASVSYLDTQVGRLLSALDDLQLANSTIIAFTSDHGWALGEHGEWAKYSNFDVATHVPLIFYVPGRTASLPEAGEKLFPYLDPFDSASQLMEPGRQSMDLVELVSLFPTLAGLAGLQVPPRCPVPSFHVELCREGKNLLKHFRFRDLEEDPYLPG
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| Molecular Weight | 76000 |
| Chemical Formula | C2654H4000N688O774S14 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 44 ± 19 minutes |
| Description | Recombinant (from human cell line) form of human lysosomal enzyme, iduronate-2-sulfatase. Idursulfase is a 525-amino acid glycoprotein, which contains 8 N-linked glycosylation sites, occupied by complex oligosaccharide structures. Its enzyme activity depends on the post-translational modification of a specific cysteine to formylglycine. |
| Indication/Disease | For the treatment of Hunter syndrome in adults and children ages 5 and older. |
| Pharmacodynamics | Idursulfase is a purified form of the lysosomal enzyme human iduronate-2-sulfatase of recombinant DNA origin. It is designed to replace the natural enzyme, increasing catabolism of certain accumulated glycosaminoglycans (GAG), which abnormally accumulate in multiple tissue types in patients with mucopolysaccharidosis II (MPS-II, or Hunter syndrome). |
| Mechanism of Action | Hunter's Syndrome is an X-linked recessive disease caused by insufficient levels of the lysosomal enzyme iduronate-2-sulfatase. This enzyme cleaves the terminal 2-O-sulfate moieties from the glycosaminoglycans (GAG) dermatan sulfate and heparan sulfate. Due to the missing or defective iduronate-2-sulfatase enzyme in patients with Hunter's Syndrome, GAG progressively accumulate in the lysosomes of a variety of cells, leading to cellular engorgement, organomegaly, tissue destruction and organ system dysfunction. Treatment of Hunter's Syndrome patients with idursulfase provides exogenous enzyme for uptake into cellular lysosomes. Targeting of idursulfase to the lysosome occurs by endocytosis from the cell surface. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow specific binding of the enzymes to the M6P receptors on the cell surface, leading to cellular internalization of the enzyme, targeting to intracellular lysosomes and subsequent catabolism of accumulated GAG. |
| Toxicity | There is no experience with overdosage of Idursulfase in humans. Single intravenous doses of idursulfase up to 20 mg/kg were not lethal in male rats and cynomolgus monkeys (approximately 6.5 and 13 times, respectively, of the recommended human dose based on body surface area) and there were no clinical signs of toxicity. |
| Metabolism | NA |
| Absorption | NA |
| NA |
| Clearance | 3 mL/min/kg [Patients (7.7 - 27 years) with Hunter syndrome with treatment week 1(0.5 mg/kg ELAPRASE administered weekly as a 3-hour infusion)] . 3.4 mL/min/kg [patients (7.7 - 27 years) with Hunter syndrome with treatment week 27 (0.5 mg/kg ELAPRASE administered weekly as a 3-hour infusion)] |
| Categories | Alimentary Tract and Metabolism,Enzymes,Enzymes and Coenzymes,Esterases,Hydrolases,Hydrolytic Lysosomal Glycosaminoglycan-specific Enzyme,Sulfatases |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Dermatan sulfate,Heparan sulfate,Perilipin-3 |
| Brand Name | Elaprase |
| Company | SHIRE |
| Brand Description | SHIRE |
| Prescribed For | indicated for patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II). ELAPRASE has been shown to improve walking capacity in patients 5 years and older. The safety and efficacy of ELAPRASE have not been established in pediatric patients less than 16 months of age |
| Chemical Name | NA |
| Formulation | Each vial contains an extractable volume of 3 mL with an idursulfase concentration of 2 mg/mL at a pH of approximately 6. Each vial contains 6 mg idursulfase, sodium chloride (24 mg), sodium phosphate monobasic monohydrate (6.75 mg), sodium phosphate dibasic heptahydrate (2.97 mg), and polysorbate 20 (0.66 mg). ELAPRASE does not contain preservatives. Each vial is for single use only. |
| Physical Appearance | Sterile, nonpyrogenic clear to slightly opalescent, colorless solution that must be diluted prior to administration in 0.9% Sodium Chloride Injection, USP |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | dosage regimen of ELAPRASE is 0.5 mg per kg of body weight administered once weekly as an Intravenous infusion. |
| Contraindication | Life-threatening anaphylactic reactions have occurred in some patients during and up to 24 hours after ELAPRASE infusions. Anaphylaxis, presenting as respiratory distress, hypoxia, hypotension, urticaria and/or angioedema of throat or tongue have been reported to occur during and after ELAPRASE infusions, regardless of duration of the course of treatment. Closely observe patients during and after ELAPRASE administration and be prepared to manage anaphylaxis. Inform patients of the signs and symptoms of anaphylaxis and have them seek immediate medical care should symptoms occur. Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions, and require additional monitoring |
| Side Effects | Bone or muscle pain, chest pain, chills, cough, fast, pounding, or irregular heartbeat or pulse, feeling of warmth, fever, headache, hives or welts, itching, rash, redness of the face, neck, arms, and occasionally, upper chest redness of the skin, sneezing, sore throat, tightness in the chest, unusual tiredness or weakness. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |