Drug: Asparaginase - Elspar®
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Summary (Dosage and administration)1:
Note: Preferred route: Intramuscular (IM).
DOSAGE AND ADMINISTRATION
Stability / Miscellaneous
INDICATIONS AND USAGE
Elspar is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL).
Mechanism of Action
The mechanism of action of Elspar is thought to be based on selective killing of leukemic cells due to depletion of plasma asparagine. Some leukemic cells are unable to synthesize asparagine due to a lack of asparagine synthetase and are dependent on an exogenous source of asparagine for survival. Depletion of asparagine, which results from treatment with the enzyme L-asparaginase, kills the leukemic cells. Normal cells, however, are less affected by the depletion due to their ability to synthesize asparagine.
The relationship between asparaginase activity and asparagine levels has been studied in clinical trials. In previously untreated, standard-risk ALL patients treated with native asparaginase in whom plasma enzyme activity was greater than 0.1 International Units/mL, plasma asparagine levels decreased from a pretreatment average level of 41 µM to less than 3 µM. In this study, cerebrospinal fluid asparagine levels in patients treated with asparaginase decreased from 2.8 µM (pretreatment) to 1.0 µM and 0.3 µM at day 7 and day 28 of induction, respectively.
In a study in patients with metastatic cancer and leukemia, daily intravenous administration of L-asparaginase resulted in a cumulative increase in plasma levels. Plasma half-life varied from 8 to 30 hours. Apparent volume of distribution was slightly greater than the plasma volume. Asparaginase levels in cerebrospinal fluid were less than 1% of concurrent plasma levels.
In a study in which patients with leukemia and metastatic cancer received intramuscular L-asparaginase, peak plasma levels of asparaginase were reached 14 to 24 hours after dosing. Plasma half-life was 34 to 49 hours.
Elspar was evaluated 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 evaluable 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.
2. DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
The recommended dose of Elspar is 6,000 International Units/m2 intramuscularly (IM) or intravenously (IV) three times a week.
2.2 Instructions for Administration
When Elspar is administered IM, the volume at a single injection site should be limited to 2 mL. If a volume greater than 2 mL is to be administered, two injection sites should be used. Discard unused portion.
When administered IV, give Elspar over a period of not less than thirty minutes through the side arm of an infusion of Sodium Chloride Injection or Dextrose Injection 5% (D5W). Discard unused portion.
2.3 Preparation and Handling Precautions
For IM administration, reconstitute Elspar by adding 2 mL Sodium Chloride Injection to the 10,000 unit vial. Withdraw volume of reconstituted Elspar containing calculated dose into sterile syringe. The reconstituted solution contains 5,000 international units (IU)/mL.
For IV administration, reconstitute Elspar by adding 5 mL Sterile Water for Injection or Sodium Chloride Injection to the 10,000 unit vial. Withdraw volume of reconstituted Elspar containing calculated dose into sterile syringe. The reconstituted solution contains 2,000 IU/mL.
Use reconstituted Elspar within eight hours.
Parenteral drug products should be inspected visually for particulate matter, cloudiness or discoloration prior to administration, whenever solution and container permit. If any of these are present, discard the solution. However, occasionally, a very small number of gelatinous fiber-like particles may develop on standing. Filtration through a 5.0 micron filter during administration will remove the particles with no resultant loss in potency.
3. DOSAGE FORMS AND STRENGTHS
10,000 International Units as lyophilized powder in single-use vial.
HOW SUPPLIED/STORAGE AND HANDLING
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.
[PACKAGE INSERT DATA] :
Lundbeck Inc., Deerfield, IL 60015, U.S.A.
ELSPAR (asparaginase) injection, powder, lyophilized, for solution Package
Revised: April 2010.
® Trademark of Lundbeck Inc.
2) Solimando, Dominic A. Drug Information Handbook for Oncology: A Complete Guide to Combination Chemotherapy Regimens, 8th ed. Hudson, OH: Lexi-Comp, Inc.; 2010.
|The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.|