CEREZYME- imiglucerase injection, powder, lyophilized, for solution
Genzyme Corporation
Cerezyme�
(imiglucerase for injection)
DESCRIPTION
Cerezyme� (imiglucerase for injection) is an analogue of the human enzyme β-glucocerebrosidase, produced by recombinant DNA technology. β-Glucocerebrosidase (β-D-glucosyl-N-acylsphingosine glucohydrolase, E.C. 3.2.1.45) is a lysosomal glycoprotein enzyme which catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide.
Cerezyme� is produced by recombinant DNA technology using mammalian cell culture (Chinese hamster ovary). Purified imiglucerase is a monomeric glycoprotein of 497 amino acids, containing 4 N-linked glycosylation sites (Mr = 60,430). Imiglucerase differs from placental glucocerebrosidase by one amino acid at position 495, where histidine is substituted for arginine. The oligosaccharide chains at the glycosylation sites have been modified to terminate in mannose sugars. The modified carbohydrate structures on imiglucerase are somewhat different from those on placental glucocerebrosidase. These mannose-terminated oligosaccharide chains of imiglucerase are specifically recognized by endocytic carbohydrate receptors on macrophages, the cells that accumulate lipid in Gaucher disease.
Cerezyme� is supplied as a sterile, non-pyrogenic, white to off-white lyophilized product. The quantitative composition of the lyophilized drug is provided in the following table:
Ingredient 200 Unit Vial 400 Unit Vial
*
This provides a respective withdrawal dose of 200 and 400 units of imiglucerase.
Imiglucerase (total amount)* 212 units 424 units
Mannitol 170 mg 340 mg
Sodium Citrates
(Trisodium Citrate)
(Disodium Hydrogen Citrate) 70 mg
(52 mg)
(18 mg) 140 mg
(104 mg)
(36 mg)
Polysorbate 80, NF 0.53 mg 1.06 mg
Citric Acid and/or Sodium Hydroxide may have been added at the time of manufacture to adjust pH.
An enzyme unit (U) is defined as the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate para-nitrophenyl-β-D-glucopyranoside (pNP-Glc) per minute at 37�C. The product is stored at 2-8�C (36-46�F). After reconstitution with Sterile Water for Injection, USP, the imiglucerase concentration is 40 U/mL (see DOSAGE AND ADMINISTRATION for final concentrations and volumes). Reconstituted solutions have a pH of approximately 6.1.
CLINICAL PHARMACOLOGY
Mechanism of Action/Pharmacodynamics
Gaucher disease is characterized by a deficiency of β-glucocerebrosidase activity, resulting in accumulation of glucocerebroside in tissue macrophages which become engorged and are typically found in the liver, spleen, and bone marrow and occasionally in lung, kidney, and intestine. Secondary hematologic sequelae include severe anemia and thrombocytopenia in addition to the characteristic progressive hepatosplenomegaly, skeletal complications, including osteonecrosis and osteopenia with secondary pathological fractures. Cerezyme� (imiglucerase for injection) catalyzes the hydrolysis of glucocerebroside to glucose and ceramide. In clinical trials,Cerezyme improved anemia and thrombocytopenia, reduced spleen and liver size, and decreased cachexia to a degree similar to that observed with Ceredase� (alglucerase injection).
