Asparaginase
Pronunciation: (as-PAR-a-jin-ase)Class: Enzyme, Antineoplastic agent
Trade Names
Elspar
- Injection, lyophilized powder for solution 10,000 units
Pharmacology
Asparaginase contains the enzyme L-asparagine amidohydrolase. In a significant number of patients with acute leukemia, the malignant cells depend on exogenous asparagine for survival. Administration of asparaginase hydrolyzes serum asparagine to nonfunctional aspartic acid and ammonia, depriving tumor cells of a required amino acid. Tumor cell proliferation is blocked.
Pharmacokinetics
Absorption
IMT max is 14 to 24 h.
Distribution
CSF levels were less than 1%.
Elimination
IVHalf-life is 8 to 30 h.
IMHalf-life is 34 to 49 h.
Indications and Usage
For the treatment of patients with acute lymphoblastic leukemia (ALL) as a component of a multiagent chemotherapeutic regimen.
Contraindications
Serious allergic reactions to asparaginase or other Escherichia coli –derived L-asparaginases; serious thrombosis, pancreatitis, and serious hemorrhagic events with prior L-asparaginase therapy.
Dosage and Administration
ALLAdults
IM or IV 6,000 units/m 2 3 times weekly.
Children younger than 16 y of ageIM 6,000 units/m 2 3 times weekly for a total of 9 doses.
General Advice
- Use reconstituted solution within 8 h and only if clear.
- A small number of gelatinous fiber-like particles may develop upon standing. Filtration through a 5 micron filter during administration will remove the particles with no loss of potency.
- IM
- Reconstitute by adding 2 mL of sodium chloride injection to the vial. The reconstituted solution contains 5,000 units/mL.
- The volume at a single injection site should be limited to 2 mL. If a volume greater than 2 mL is to be administered, use 2 injection sites.
- IV
- Reconstitute by adding 5 mL of sterile water for injection or sodium chloride injection to the vial. The reconstituted solution contains 2,000 units/mL.
- Administer over a period of not less than 30 min through the side arm of an infusion of sodium chloride injection or dextrose 5% injection.
Storage/Stability
Store unreconstituted vials between 36° and 46°F. Store unused reconstituted solution between 36° and 46°F; discard after 8 h, or sooner if cloudy. Discard unused portion.
Drug Interactions
Vaccines, liveThe risk of live vaccine–induced adverse reactions may be increased by coadministration of asparaginase. Use of live vaccines in patients receiving asparaginase should be deferred.
Adverse Reactions
Cardiovascular
Sagittal sinus thrombosis, thrombosis.
CNS
CNS hemorrhages, CNS thrombosis, coma, hallucinations, seizures.
Hematologic
Coagulopathy, decreased fibrinogen, decreased protein C, decreased protein S and antithrombin III, increased PT, increased PTT.
Hepatic
Elevated transaminases, hepatotoxicity (some fatal), hyperbilirubinemia, liver function abnormalities.
Hypersensitivity
Anaphylaxis and serious allergic reactions.
Metabolic
Glucose intolerance, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia.
Miscellaneous
Azotemia, pancreatitis (fulminant or fatal).
Precautions
MonitorMonitor coagulation parameters, and serum glucose and evaluate hepatic enzymes and bilirubin at baseline and periodically during and after treatment. Observe patient for 1 h after administration of asparaginase in a setting with necessary agents to treat anaphylaxis (eg, antihistamines, epinephrine, IV steroids, oxygen). |
Pregnancy
Category C .
Lactation
Undetermined.
Hypersensitivity
Serious allergic reactions may occur. This risk is higher in patients with prior exposure to asparaginase or other E. coli –derived L-asparaginase.
Coagulopathy
Hypofibrinogenemia, increased PTT, and increased PT can occur. CNS hemorrhages have been observed.
Glucose intolerance
May occur during treatment and irreversible in some cases.
Hepatic effects
Fulminant hepatic failure, hepatotoxicity and abnormal liver function, including elevations of AST, ALT, alkaline phosphatase, bilirubin (direct and indirect), and depression of serum albumin and plasma fibrinogen may occur.
Immunogenicity
Development of binding and/or neutralizing antibodies to asparaginase may occur.
Pancreatitis
Pancreatitis, in some cases fulminant or fatal, may occur.
Thrombosis
Serious thrombotic events, including sagittal sinus thrombosis, may occur.
Patient Information
- Advise patient, family, or caregiver that medication will be used in combination with other agents to achieve maximum benefit possible.
- Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; acute difficulty in breathing or shortness of breath; new onset of chest pain; severe headache; swelling of the face, arms, or legs; seizures; changes in mental status; severe abdominal pain.
- Advise patients to inform their health care provider if they experience excessive thirst or an increase in the volume or frequency of urination.
- Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
Copyright © 2009 Wolters Kluwer Health.
