Usage
Asparaginase is an antineoplastic (anti-cancer) enzyme used primarily in the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). It is often part of a multi-agent chemotherapy regimen. Asparaginase works by breaking down asparagine, an amino acid essential for cell growth. Since ALL cells cannot synthesize asparagine, they rely on the body’s supply. Depleting asparagine levels through asparaginase administration selectively targets and inhibits the proliferation of these leukemic cells.
Alternate Names
- Crisantaspase
- Colaspase
- Asparaginase Erwinia chrysanthemi (recombinant)-rywn
- Spectrila
- Elspar
- Erwinase
- Oncaspar
- RYLAZE
How It Works
Pharmacodynamics: Asparaginase hydrolyzes asparagine into aspartic acid and ammonia. Normal cells can synthesize asparagine, but leukemic lymphoblasts cannot, making them vulnerable to asparagine depletion. This depletion disrupts protein synthesis and leads to cell death.
Pharmacokinetics: Asparaginase is administered intravenously or intramuscularly. Intramuscular administration reaches peak plasma levels in 14–24 hours. Distribution is primarily within the intravascular space, with a half-life varying depending on the specific formulation (8–30 hours intravenously, 39-49 hours intramuscularly). It is metabolized by the serum and tissues and is not excreted in urine.
Mode of Action: The enzyme exerts its antineoplastic effect by depleting serum asparagine, which leads to inhibition of protein synthesis in leukemic cells.
Elimination: Asparaginase is not renally excreted and is broken down by the serum and tissues.
Dosage
Standard Dosage
Adults:
- E. coli formulations: 5,000–10,000 U/m² IV/IM every 3 days, or 6,000 U/m² IM/IV 3 times weekly.
- Erwinia chrysanthemi formulations: 25 mg/m² IM every 48 hours, or 25 mg/m² IM Mondays and Wednesdays, and 50 mg/m² on Fridays.
- Pegaspargase: 2,500 IU/m² IM/IV every 14 days.
Children (over 1 year):
Similar to adult dosing for E. coli and Erwinia asparaginase. For children younger than 1 year, dosing is based on body surface area and age, with higher doses used in infants less than 6 months.
Special Cases:
- Elderly Patients: Limited data; adjust dose with caution based on organ function.
- Patients with Renal Impairment: No dose adjustment typically necessary.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Use with caution in mild-to-moderate impairment, with close monitoring of liver function.
- Patients with Comorbid Conditions: Close monitoring is essential, particularly for patients with diabetes, pancreatic insufficiency, or a history of thrombosis.
Clinical Use Cases
The use of asparaginase is primarily indicated in the treatment of acute lymphoblastic leukemia (ALL) as part of a multi-agent chemotherapy regimen. There are no specific dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations outside of ALL treatment protocols.
Dosage Adjustments
Dosage adjustments should be made based on patient-specific factors such as hepatic function, age (in infants), and history of hypersensitivity reactions. Therapeutic drug monitoring, including measurement of asparaginase activity levels, is recommended.
Side Effects
Common Side Effects:
Nausea, vomiting, loss of appetite, fatigue, fever, chills, rash, abdominal pain, headache, and injection site reactions.
Rare but Serious Side Effects:
Pancreatitis, hepatotoxicity (including liver failure), thrombosis (including sagittal sinus thrombosis), hemorrhage, hypersensitivity reactions (including anaphylaxis), hyperglycemia, and encephalopathy.
Long-Term Effects:
Chronic complications can include impaired liver function, diabetes, and increased risk of infections.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe pancreatitis, thrombotic events, and hepatic failure require immediate intervention.
Contraindications
- History of serious hypersensitivity to asparaginase.
- History of pancreatitis.
- Severe hepatic impairment.
- History of serious thrombosis or hemorrhage associated with prior asparaginase therapy.
Drug Interactions
Asparaginase can interact with various medications including methotrexate, vincristine, prednisone, and other chemotherapy agents. It can also interact with medications metabolized by the liver, impacting their efficacy and potential side effects. Consult comprehensive drug interaction resources before co-administering.
Pregnancy and Breastfeeding
Asparaginase can cause fetal harm. Effective contraception is essential during and for several months after treatment. Breastfeeding is generally not recommended while receiving asparaginase. Consult a healthcare professional for personalized advice.
Drug Profile Summary
- Mechanism of Action: Depletes serum asparagine, inhibiting protein synthesis in susceptible cells.
- Side Effects: Nausea, vomiting, fatigue, pancreatitis, hepatotoxicity, thrombosis, hemorrhage, hypersensitivity.
- Contraindications: Hypersensitivity, pancreatitis, severe hepatic impairment, prior thrombosis/hemorrhage with asparaginase.
- Drug Interactions: Methotrexate, vincristine, prednisone, other chemotherapy agents, liver-metabolized drugs.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; breastfeeding not recommended.
- Dosage: Varies depending on formulation and patient factors; consult specific product information.
- Monitoring Parameters: Asparaginase activity levels, liver function tests, blood glucose, coagulation parameters.
Popular Combinations
Asparaginase is frequently used in combination regimens for ALL, which typically include vincristine, prednisone, daunorubicin, and other chemotherapeutic agents.
Precautions
Close patient monitoring for side effects, especially pancreatitis, hepatotoxicity, and hypersensitivity reactions, is crucial.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Asparaginase?
A: Dosage varies depending on the specific asparaginase formulation (e.g. E. coli, Erwinia, pegylated), patient age, and body surface area. Consult specific product information for detailed dosage guidelines.
Q2: What are the most serious side effects of Asparaginase?
A: Pancreatitis, hepatotoxicity, thrombosis, hemorrhage, and hypersensitivity reactions (including anaphylaxis).
Q3: How does Asparaginase work?
A: It depletes asparagine, an amino acid essential for leukemic cell growth.
Q4: Can Asparaginase be given during pregnancy?
A: No, it is contraindicated in pregnancy due to the risk of fetal harm.
Q5: What are the common drug interactions with Asparaginase?
A: Interactions can occur with methotrexate, vincristine, prednisone, and other chemotherapy agents, as well as with drugs metabolized by the liver.
Q6: How should hypersensitivity reactions to Asparaginase be managed?
A: Discontinue the drug immediately and provide supportive care. Consider switching to a different formulation (e.g., Erwinia chrysanthemi if hypersensitivity to E. coli asparaginase occurs).
Q7: What monitoring parameters are essential during Asparaginase therapy?
A: Monitor asparaginase activity levels, liver function tests, blood glucose, coagulation parameters, amylase, and lipase.
Q8: What is the role of Asparaginase in ALL treatment?
A: Asparaginase is a cornerstone of ALL treatment, contributing significantly to improved outcomes. It is typically used as part of a combination chemotherapy regimen.
Q9: What patient education should be provided regarding Asparaginase?
A: Counsel patients on potential side effects, the importance of adherence to the treatment plan, and the need for regular monitoring. Emphasize the importance of seeking medical attention immediately if any signs of hypersensitivity, pancreatitis, or other serious side effects appear.
A: Yes, formulations derived from E. coli and Erwinia chrysanthemi, as well as pegylated forms (pegaspargase) are available. Each formulation has distinct pharmacokinetic properties and toxicity profiles.
