Generic
L-Asparginase
2 brands available in the market
At a glance
L-Asparginase injection is used as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL). It kills leukemic cells by depleting plasma asparagine.
Description
L-Asparginase is an enzyme known as L-Asparagine Amidohydrolase (EC-2). Its mechanism of action is based on the selective killing of leukemic cells due to the 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 resulting from L-Asparginase treatment kills the leukemic cells. Normal cells are less affected due to their ability to synthesize asparagine. L-Asparginase is not absorbed from the GI tract and must be administered IM or IV.
Indications
- Acute lymphoblastic leukemia (ALL) - as a component of multi-agent chemotherapeutic regimens
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
Enzyme Therapy
Pharmacology
The mechanism of action of L-Asparginase is based on the selective killing of leukemic cells due to the depletion of plasma asparagine. Leukemic cells are unable to synthesize asparagine (due to lack of asparagine synthetase) and depend on exogenous asparagine for survival. L-Asparginase converts asparagine to ammonia and aspartic acid, depleting plasma asparagine and causing leukemic cell death. Normal cells can synthesize asparagine and are less affected.
Mechanism of action
Kills leukemic cells by depleting plasma asparagine.
Dosage
Adult Dose:
- As a component of multiple-agent induction regimens
- IV administration: Infuse over a period of not less than 30 minutes
- IM administration: Limit volume to 2 ml per single injection site
- Dosage and schedule are determined by the physician
Child Dose: Dosage is determined as per physician's advice.
Administration
- For IV or IM administration only
- IV administration: Give slowly over 30 minutes through the side arm of an already running infusion of sodium chloride or 5% dextrose
- IM administration: Limit to 2 ml per single injection site; use two sites if volume exceeds 2 ml
- This drug may be toxic; handle and administer with care
- Avoid inhalation of dust/aerosols and contact with skin or eyes
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose.
Side effects
Serious Adverse Reactions:
- Anaphylaxis and serious allergic reactions
- Serious thrombosis
- Pancreatitis
- Glucose intolerance
- Coagulopathy
- Hepatotoxicity and abnormal liver function
Common Adverse Reactions:
- Allergic reactions (including anaphylaxis)
- Hyperglycemia
- Pancreatitis
- CNS thrombosis
- Coagulopathy
- Hyperbilirubinemia
- Elevated transaminases
Precautions & warnings
- This drug may be toxic; handle and administer with care
- Have epinephrine, oxygen and IV steroids ready for anaphylaxis
- May interfere with enzymatic detoxification in the liver
- Use during pregnancy only if clearly needed
- If used during lactation, decide whether to discontinue nursing or the drug
Contraindications
- Hypersensitivity to L-Asparginase or any of its components
Drug interactions
- May diminish or abolish the effect of Methotrexate
- Concurrent IV administration with Vincristine and Prednisolone may increase toxicity
- Interferes with thyroid function tests (reduces thyroxine-binding globulin)
Food interactions
No food interactions applicable (parenteral use).
Use in pregnancy
Pregnancy Category: C
Animal studies have shown retarded maternal and fetal weight gain, resorptions, gross and skeletal abnormalities. No adequate and well-controlled studies in pregnant women. Use only if clearly needed.
Pregnancy Category: C — always consult a doctor before taking during pregnancy.
Use in lactation
It is not known whether L-Asparginase is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.
Pediatric use
Safety and efficacy in children are not fully established; use as directed by physician.
Geriatric use
No sufficient studies in patients aged 65 and older; use with caution.
Renal / hepatic impairment
Use with caution in patients with hepatic or renal impairment; dose adjustment may be required.
Overdose effects
No specific overdose information available; excessive doses may increase adverse reactions.
Storage conditions
Store refrigerated at 2-8°C; protect from light; do not freeze; reconstituted solution should be used within 8 hours.
Chemical structure
L-Asparginase