"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
ADAGEN® (pegademase bovine) Injection is indicated for enzyme replacement therapy for adenosine deaminase (ADA) deficiency in patients with severe combined immunodeficiency disease (SCID) who are not suitable candidates for – or who have failed – bone marrow transplantation. ADAGEN® (pegademase bovine) Injection is recommended for use in infants from birth or in children of any age at the time of diagnosis. ADAGEN® (pegademase bovine) Injection is not intended as a replacement for HLA identical bone marrow transplant therapy. ADAGEN® (pegademase bovine) Injection is also not intended to replace continued close medical supervision and the initiation of appropriate diagnostic tests and therapy (e.g., antibiotics, nutrition, oxygen, gammaglobulin) as indicated for intercurrent illnesses.
DOSAGE AND ADMINISTRATION
Before prescribing ADAGEN®(pegademase bovine) Injection the physician should be thoroughly familiar with the details of this prescribing information. For further information concerning the essential monitoring of ADAGEN® (pegademase bovine) Injection therapy, the prescribing physician should contact Sigma-Tau Pharmaceuticals, Inc., Gaithersburg, MD 20878. Telephone 1-866792-5172.
ADAGEN® (pegademase bovine) Injection is recommended for use in infants from birth or in children of any age at the time of diagnosis.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permits.
ADAGEN® (pegademase bovine) Injection should not be diluted nor mixed with any other drug prior to administration.
ADAGEN® (pegademase bovine) Injection should be administered every 7 days as an intramuscular injection. The dosage of ADAGEN® (pegademase bovine) Injection should be individualized. The recommended dosing schedule is 10 U/kg for the first dose, 15 U/kg for the second dose, and 20 U/kg for the third dose. The usual maintenance dose is 20 U/kg per week. Further increases of 5 U/kg/week may be necessary, but a maximum single dose of 30 U/kg should not be exceeded. Plasma levels of ADA more than twice the upper limit of 35 μmol/hr/mL have occurred on occasion in several patients, and have been maintained for several weeks in one patient who received twice weekly injections (20 U/kg per dose) of ADAGEN® (pegademase bovine) Injection. No adverse effects have been observed at these higher levels; there is no evidence that maintaining pre-injection plasma ADA above 35 μmol/hr/mL produces any additional clinical benefits.
Dose proportionality has not been established and patients should be closely monitored when the dosage is increased. ADAGEN® (pegademase bovine) Injection is not recommended for intravenous administration.
The optimal dosage and schedule of administration should be established for each patient based on monitoring of plasma ADA activity levels (trough levels before maintenance injection) and biochemical markers of ADA deficiency (primarily red cell dATP content). Since improvement in immune function follows correction of metabolic abnormalities, maintenance dosage in individual patients should be aimed at achieving the following biochemical goals: 1) maintain plasma ADA activity (trough levels before maintenance injection) in the range of 15-35 μmol/hr/mL (assayed at 37°C); and 2) decline in erythrocyte dATP to ≤ 0.005-0.015 μmol/mL packed erythrocytes, or ≤ 1% of the total erythrocyte adenine nucleotide (ATP + dATP) content, with a normal ATP level, as measured in a pre-injection sample. In addition, continued monitoring of immune function and clinical status is essential in any patient with a primary immunodeficiency disease and should be continued in patients undergoing treatment with ADAGEN®(pegademase bovine) Injection.
ADAGEN® (pegademase bovine) Injection is a clear, colorless, preservative free solution for intramuscular injection. ADAGEN® is supplied as a sterile solution in single-use vials containing 375 units per 1.5 mL solution, in boxes of 4 vials (NDC-57665-00101).
Use only one dose per vial; do not re-enter the vial. Discard unused portions. Do not save unused drug for later administration. Refrigerate. Store between +2°C and +8°C (36°F and 46°F). DO NOT FREEZE. ADAGEN® (pegademase bovine) Injection should not be stored at room temperature. This product should not be used if there are any indications that it may have been frozen.
1. Hershfield MS, Buckley RH, Greenberg ML, et al. Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med 1987; 316:589-96.
2. Levy Y, Hershfield MS, Fernandez-Mejia C, Polmar ST, Scudiery D, Berger M, Sorensen RU. Adenosine deaminase deficiency with late onset of recurrent infections: response to treatment with polyethylene glycolmodified adenosine deaminase. J Pediatr 1988; 113:312-17.
3. Kredich NM, Hershfield MS. Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. 6th ed. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease. New York: McGraw Hill, 1989; 1045-75.
4. Hirschhorn R. Inherited enzyme deficiencies and immunodeficiency: adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies. Clin Immunol Immunopathol 1986; 40:157-65.
5. Hirschhorn R, Roegner-Maniscalco V, Kuritsky L, Rosen FS. Bone marrow transplantation only partially restores purine metabolites to normal adenosine deaminase-deficient patients. J Clin Invest 1981; 68:1387-93.
6. Polmar AH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, Hirschhorn R. Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med 1976; 295:1337-43.
7. Rubinstein A, Hirschhorn R, Sicklick M, Murphy RA. In vivo and in vitro effects of thymosin and adenosine deaminase on adenosine-deaminase-deficient lymphocytes. N Engl J Med 1979; 300:387-92.
8. Hirschhorn R, Papageorgiou PS, Kesarwala HH, Taft LT. Amelioration of neurologic abnormalities after “enzyme replacement” in adenosine deaminase deficiency. N Engl J Med 1980; 303:377-80.
9. Hirschhorn R, Ratech H, Rubinstein A, et al. Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency. Pediatr Res 1982; 16:362-9.
10.Polmar SH. Enzyme replacement and other biochemical approaches to the therapy of adenosine deaminase deficiency. In: Elliott K, Whelan J, eds. Enzyme defects and immune dysfunction. Amsterdam: Excerpta Medica, 1979; 213-30.
Manufactured by Sigma-Tau PharmaSource, Inc., Indianapolis, IN 46268. Distributed by Sigma-Tau Pharmaceuticals, Inc., Gaithersburg, MD 20878. sigma-tau, Pharmaceuticas, Inc., Gaithersburg, MD 20878.
Manufactured by: Sigma-tau pharmaceuticals Inc. Gaithersburg, MD 20878. Revised 2013This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/23/2014
Additional Adagen Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.