No relevant studies addressing mutagenic potential have been conducted. Elspar did not exhibit a mutagenic effect when tested against Salmonella typhimurium strains in the Ames assay.
No studies have been performed on impairment of fertility.

13.2  Animal Toxicology
Edema and necrosis of pancreatic islets were observed in rabbits following a single, intravenous injection of 12,500 to 50,000 International Units Elspar/kg (approximately equivalent to 25 to 100-fold the recommended human dose, when adjusted for total body surface area). These changes were not reflective of pancreatitis, and were not observed in rabbits following a single intravenous injection of 1000 International Units/kg (approximately equivalent to two times the recommended human dose, when adjusted for total body surface area).

14  CLINICAL STUDIES
Elspar was eva luated in an open-label, multi-center, single-arm study in which 823 patients less than 16 years of age with previously untreated acute lymphoblastic or acute undifferentiated leukemia received Elspar as a component of multi-agent chemotherapy for induction of first remission. Elspar was administered at a dose of 6,000 International Units/m2 intramuscularly 3 times a week for a total of 9 doses.  Of 815 eva luable patients, 758 (93%) achieved a complete remission.  In a previous study, in a similar patient population, which utilized an initial induction chemotherapy regimen containing the same agents without Elspar, 429 of 499 (86%) patients achieved a complete remission.

16  HOW SUPPLIED/STORAGE AND HANDLING
Dosage Form

NDC 67386-411-51

10,000 International Units as lyophilized powder in single dose vial individually packaged in a carton.

Storage and Handling

Keep vials refrigerated at 2-8°C (36-46°F).

Elspar does not contain a preservative. Store unused, reconstituted solution at 2-8°C (36-46°F) and discard after eight hours, or sooner if it becomes cloudy.

17  PATIENT COUNSELING INFORMATION
Advise patients to contact health care professional immediately to report any of the following:

swelling of the face, arms or legs, with or without pain in the arm or leg
acute difficulty in breathing/shortness of breath
severe headache, seizures, change in mental status
new onset chest pain
severe abdominal pain
Advise patients to inform their healthcare professional of:

excessive thirst or an increase in the volume or frequency of urination
pregnancy
Lundbeck Inc., Deerfield, IL 60015, U.S.A.

U.S. Lic. No. 1822

® Trademark of Lundbeck Inc.

Revised: February 2010

PRINCIPAL DISPLAY PANEL
NDC 67386-411-51

ELSPAR 
asparaginase   injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67386-411
Route of Administration INTRAMUSCULAR, INTRAVENOUS DEA Schedule      
 
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ASPARAGINASE (ASPARAGINASE)  ASPARAGINASE 10000 [iU]
 
Inactive Ingredients
Ingredient Name Strength
MANNITOL  
 
Product Characteristics
Color      Score     
Shape  Size&