VPRIV- velaglucerase alfa injection, powder, lyophilized, for solution
Shire US Manufacturing Inc.
1 INDICATIONS AND USAGE
VPRIV is indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Starting Dosage in Patients Na�ve to Enzyme Replacement Therapy
VPRIV should be administered under the supervision of a healthcare professional. The recommended starting VPRIV dosage in na�ve adults and na�ve pediatric patients 4 years of age and older is 60 Units/kg administered every other week as a 60-minute intravenous infusion. The dosage can be adjusted based on achievement and maintenance of each patient's therapeutic goals.
2.2 Switching from Imiglucerase to VPRIV
Adults and pediatric patients 4 years of age and older currently being treated on a stable dosage of imiglucerase for type 1 Gaucher disease may be switched to VPRIV by starting treatment with VPRIV at the previous imiglucerase dosage two weeks after the last imiglucerase dose. VPRIV should be administered under the supervision of a healthcare professional as a 60-minute intravenous infusion. The dosage can be adjusted based on achievement and maintenance of each patient's therapeutic goals.
2.4 Important Administration Instructions
Administer the diluted VPRIV solution through an in-line low protein-binding 0.2μm filter over 60 minutes. Do not infuse VPRIV with other products in the same infusion tubing because the compatibility of a VPRIV solution with other products has not been evaluated.
2.5 Premedication to Reduce Risk of Subsequent Hypersensitivity Reactions
Consider pre-treatment with antihistamines and/or corticosteroids in patients who exhibited symptoms of hypersensitivity associated with prior VPRIV infusions. Appropriate medical support should be readily available when VPRIV is administered [see Warnings and Precautions (5.1)].
3 DOSAGE FORMS AND STRENGTHS
VPRIV for injection: sterile, white to off-white, lyophilized powder (400 Units in single-use vials) for reconstitution with Sterile Water for Injection, USP, to yield a final concentration of 100 Units/mL.
DESCRIPTION
The active ingredient of VPRIV is velaglucerase alfa, which is produced by gene activation technology in a human fibroblast cell line. Velaglucerase alfa is a glycoprotein of 497 amino acids; with a molecular weight of approximately 63 kDa. Velaglucerase alfa has the same amino acid sequence as the naturally occurring human enzyme, glucocerebrosidase. Velaglucerase alfa contains 5 potential N-linked glycosylation sites; four of these sites are occupied by glycan chains. Velaglucerase alfa contains predominantly high mannose-type N-linked glycan chains. The high mannose type N-linked glycan chains are specifically recognized and internalized via the mannose receptor present on the surface on macrophages, the cells that accumulate glucocerebroside in Gaucher disease. Velaglucerase alfa catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide in the lysosome.
VPRIV is a hydrolytic lysosomal glucocerebroside-specific enzyme. VPRIV is dosed by Units/kg, where one Unit of enzyme activity is defined as the quantity of enzyme required to convert one micromole of p-nitrophenyl �-D-glucopyranoside to p-nitrophenol per minute at 37�C.
VPRIV is supplied as a sterile, preservative free, lyophilized powder in single-use vials, each containing 400 Units, for intravenous use
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene, which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency causes an accumulation of glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells". Velaglucerase alfa catalyzes the hydrolysis of glucocerebroside, reducing the amount of accumulated glucocerebroside. In clinical trials VPRIV reduced spleen and liver size, and improved anemia and thrombocytopenia.
In this lysosomal storage disorder (LSD), clinical features are reflective of the accumulation of Gaucher cells in the liver, spleen, bone marrow, and other organs. The accumulation of Gaucher cells in the liver and spleen leads to organomegaly. Presence of Gaucher cells in the bone marrow and spleen lead to clinically significant anemia and thrombocytopenia.
