Asparaginase
Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)
Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
A bacterial enzyme that destroys blood asparagine, which leukaemic lymphoblasts need; a pillar of ALL treatment. Watch for allergy, pancreatitis and clots.
Also called: L-asparaginase, Escherichia coli asparaginase, Erwinia chrysanthemi asparaginase
Quick facts
- Group
- Other antineoplastics (differentiating agents, asparaginases, proteasome inhibitors)
- Target
- Plasma L-asparagine (the drug is the enzyme L-asparaginase)
- Used for
- Acute lymphoblastic leukaemia
- Key effects
- Allergic reactions · Nausea · High blood glucose
- Monitor
- Signs of allergy during · Glucose · Liver tests
- ATC
- L01XX02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows Escherichia coli L-asparaginase II, the enzyme itself, with aspartate (the product of the reaction) in its active site.
Most normal cells make enough asparagine with asparagine synthetase, but leukaemic lymphoblasts have too little of this enzyme and depend on asparagine from the plasma. Asparaginase hydrolyses circulating asparagine to aspartic acid and ammonia. Without asparagine the lymphoblasts cannot make proteins and die. Resistance appears when the tumour cells induce asparagine synthetase. Normal tissues that make many proteins (liver, pancreas) are also affected, which explains low albumin, clotting changes and high glucose.
- Lymphoblasts lack asparagine synthetase
- The enzyme breaks plasma asparagine into aspartate + ammonia
- No asparagine: protein synthesis stops
- Leukaemic cells die
Indications
- Acute lymphoblastic leukaemia, in combination chemotherapy (with vincristine, a corticosteroid and others). Acute leukaemia (AML and ALL) →
- A type of non-Hodgkin lymphoma (lymphoblastic); the Erwinia enzyme is used after allergy to the Escherichia coli enzyme. Non-Hodgkin lymphoma →
Adverse effects
Common
- Allergic reactions: hives, rash, itching
- Nausea, vomiting, loss of appetite
- High blood glucose
- Raised liver enzymes and bilirubin, low albumin
- Clotting test changes (low fibrinogen)
- High triglycerides
Contraindications
- Previous serious allergy to the same asparaginase
- Previous pancreatitis, serious thrombosis or serious bleeding during asparaginase treatment
- Severe liver disease
Key interactions
- Methotrexate
- Asparaginase given shortly after methotrexate cancels methotrexate's antitumour effect; the timing is planned in the protocol.
- Highly protein-bound drugs
- Lower albumin can raise their free fraction and speed their clearance.
- Hormonal contraceptives
- A non-hormonal method is advised during treatment and for months after.
What is monitored
- Signs of allergy during and after each dose
- Amylase or lipase and abdominal pain (pancreatitis)
- Glucose
- Liver tests, bilirubin and albumin
- Fibrinogen and other coagulation tests; signs of clots or bleeding
Administration and safety
- Several asparaginase products exist (Escherichia coli, Erwinia, pegylated); they are not interchangeable, so check the exact product and route.
- Observe the patient after each dose with anaphylaxis drugs and equipment at hand.
- Hazardous drug: prepared and disposed of following cytotoxic handling procedures.
Pregnancy and breastfeeding
May harm the fetus; pregnancy is excluded before starting, non-hormonal contraception is used, and breastfeeding is avoided.
Nursing care
- Watch for hives, wheeze, swelling of the face or low blood pressure after each dose.
- Check glucose and ask about thirst and frequent urination.
- Ask about abdominal pain that goes to the back, vomiting (pancreatitis), headache, leg swelling or seizures (clots).
- Teaching: report yellow skin or dark urine, and use non-hormonal contraception.
Pharmacokinetics
- Absorption
- Given intramuscularly or intravenously.
- Distribution
- Stays mostly in the plasma; it lowers asparagine in the spinal fluid only partly.
- Elimination
- Cleared as a protein; antibodies against the enzyme speed its clearance and inactivate it.
- Half-life
- About one day for the Escherichia coli enzyme; the pegylated form (pegaspargase) lasts much longer.
Test yourself
Think of the answer, then tap the question to see it.
Why does asparaginase kill lymphoblasts but spare most normal cells?
Lymphoblasts lack enough asparagine synthetase and depend on plasma asparagine, which the enzyme destroys.
A child on ALL induction with asparaginase has epigastric pain radiating to the back. What test is ordered?
Serum lipase or amylase, for asparaginase-induced pancreatitis.
What is «silent inactivation»?
Antibodies neutralise the enzyme without causing allergy, so it stops working unnoticed.
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Asparaginase Erwinia Chrysanthemi (recombinant)-rywn Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.
