DESCRIPTION
ADAGEN® (pegademase bovine) Injection is a modified enzyme used for enzyme replacement therapy for the treatment of severe combined immunodeficiency disease (SCID) associated with a deficiency of adenosine deaminase.

ADAGEN® (pegademase bovine) Injection is supplied in an isotonic, pyrogen free, sterile solution, pH 7.2-7.4, for intramuscular injection only. The solution is clear and colorless. It is supplied in 1.5 mL single-dose vials.

The chemical name for ADAGEN® (pegademase bovine) Injection is (monomethoxypolyethylene glycol succinimidyl) 11-17-adenosine deaminase. It is a conjugate of numerous strands of monomethoxypolyethylene glycol (PEG), molecular weight 5,000, covalently attached to the enzyme adenosine deaminase (ADA). ADA (adenosine deaminase EC 3.5.4.4) used in the manufacture of ADAGEN® (pegademase bovine) Injection is derived from bovine intestine.

The structural formula of ADAGEN® (pegademase bovine) Injection is:

 
Each milliliter of ADAGEN® (pegademase bovine) Injection contains:
Pegademase bovine 250 units*
Monobasic sodium phosphate, USP 1.20 mg
Dibasic sodium phosphate, USP 5.58 mg
Sodium Chloride, USP 8.50 mg
Water for injection, USP q.s. to 1.0 mL

*One unit of activity is defined as the amount of ADA that converts 1μM of adenosine to inosine per minute at 25°C and pH 7.3.

CLINICAL PHARMACOLOGY

Severe Combined Immunodeficiency Disease Associated with ADA Deficiency
Severe combined immunodeficiency disease (SCID) associated with a deficiency of ADA is a rare, inherited, and often fatal disease. In the absence of the ADA enzyme, the purine substrates adenosine and 2′-deoxyadenosine accumulate, causing metabolic abnormalities that are directly toxic to lymphocytes.

The immune deficiency can be cured by bone marrow transplantation. When a suitable bone marrow donor is unavailable or when bone marrow transplantation fails, non-selective replacement of the ADA enzyme has been provided by periodic irradiated red blood cell transfusions. However, transmission of viral infections and iron overload are serious risks associated with irradiated red blood cell transfusions, and relatively few ADA deficient patients have benefitted from chronic transfusion therapy.

ADAGEN® (pegademase bovine) Injection provides specific and direct replacement of the deficient enzyme, but will not benefit patients with immunodeficiency due to other causes.

In patients with ADA deficiency, rigorous adherence to a schedule of ADAGEN® (pegademase bovine) Injection administration can eliminate the toxic metabolites of ADA deficiency and result in improved immune function. It is imperative that treatment with ADAGEN® (pegademase bovine) Injection be carefully monitored by measurement of the level of ADA activity in plasma. Monitoring of the level of deoxyadenosine triphosphate (dATP) in erythrocytes is also helpful in determining that the dose of ADAGEN® (pegademase bovine) Injection is adequate.

Actions
ADAGEN® (pegademase bovine) Injection provides specific replacement of the deficient enzyme.

In the absence of the enzyme ADA, the purine substrates adenosine, 2′-deoxyadenosine and their metabolites are toxic to lymphocytes. The direct action of ADAGEN® (pegademase bovine) Injection is the correction of these metabolic abnormalitie