as·par·a·gin·ase ( -sp r -j-n s , -nz)n. A bacterial enzyme that catalyzes the hydrolysis of asparagine and is used in the treatment of leukemia. |
asparaginase
asparaginase Warning - Hazardous drug!
Elspar, Kidrolase (CA)
Pharmacologic class: Enzyme
Therapeutic class: Antineoplastic (miscellaneous)
Pregnancy risk category C
FDA Boxed Warning
• Give in hospital under supervision of physician experienced in cancer chemotherapy, because of possibility of severe reactions (including anaphylaxis and sudden death). Be prepared to treat anaphylaxis at each administration. Prescriber must weigh drug's risks and benefits carefully for each patient.
• Follow special handling procedures.
Action
Hydrolyzes asparagine (an amino acid needed for malignant cell growth in acute lymphocytic leukemia), resulting in leukemic cell death
Availability
Injection: 10,000 international units/vial (with mannitol)
⊘Indications and dosages
➣ Acute lymphocytic leukemia (given with other drugs, such as prednisone or vincristine, as part of antineoplastic regimen)
Children: 1,000 international units/kg I.V. daily for 10 successive days, with asparaginase initiated on day 22 of regimen, or 6,000 international units/m2 I.M. on days 4, 7, 10, 13, 16, 19, 22, 25, and 28
➣ Sole agent used to induce remission of acute lymphocytic leukemia
Adults and children: 200 international units/kg I.V. daily for 28 days
➣ Drug desensitization regimen
Adults and children: Initially, 1 international unit I.V. Then double the dosage q 10 minutes until total planned daily dosage has been given.
Contraindications
• Hypersensitivity to drug
• Pancreatitis or history of pancreatitis
Precautions
Use cautiously in:
• bone marrow depression, hepatic or renal disease, CNS depression, clotting abnormalities, infection
• pregnant or breastfeeding patients
• women of childbearing age.
Administration
☞ Administer intradermal skin test as ordered at start of therapy and when drug hasn't been given for 1 week or more.
• Follow prescriber's orders for drug desensitization when indicated (usually before therapy starts and again during retreatment).
☞ Know that drug may be carcinogenic, mutagenic, or teratogenic. Follow appropriate facility policy for handling and preparing.
• Before starting drug, give allopurinol as prescribed to lower risk of neuropathy.
• Add sterile water or normal saline solution (5 ml for I.V. dose, 2 ml for I.M. dose) to powdered drug in vial.
• Filter through 5-micron filter.
• For I.V. use, inject into normal saline solution or dextrose 5% in water and infuse over 30 minutes.
• For I.M. use, give a maximum of 2 ml at any one site.
• Don't use solution unless it's clear.
☞ If drug touches skin or mucous membranes, rinse with copious amounts of water for at least 15 minutes.
• Provide adequate fluid intake to prevent tumor lysis.
| Route | Onset | Peak | Duration |
| I.V. | Immediate | Immediate | 23-33 days |
| I.M. | Immediate | 14-24 hr | 23-33 days |
Adverse reactions
CNS: confusion, drowsiness, depression, hallucinations, fatigue, agitation, headache, lethargy, irritability, seizures, coma, intracranial hemorrhage and fatal bleeding
GI: nausea, vomiting, anorexia, abdominal cramps, stomatitis, hemorrhagic pancreatitis, fulminant pancreatitis
GU: glycosuria, polyuria, uric acid nephropathy, uremia, renal failure
Hematologic: anemia, leukopenia, hypofibrinogenemia, depression of clotting factor synthesis, bone marrow depression
Hepatic: fatty liver changes, hepatotoxicity
Metabolic: hyperglycemia, hyperuricemia, hypocalcemia, hyperammonemia, hypoglycemia
Musculoskeletal: joint pain
Skin: rash, urticaria
Other: chills, fever, weight loss, hypersensitivity reactions, anaphylaxis, fatal hyperthermia
Interactions
Drug-drug. Methotrexate: decreased methotrexate efficacy
Prednisone: hyperglycemia, increased drug toxicity
Vincristine: hyperglycemia, increased drug toxicity, increased risk of neuropathy
Drug-diagnostic tests. Alanine aminotransferase, ammonia, aspartate aminotransferase, blood urea nitrogen, glucose, uric acid: increased levels
Calcium, hemoglobin, white blood cells: decreased levels
Thyroid function tests: interference with test interpretation
Patient monitoring
☞ Observe for signs and symptoms of anaphylaxis.
☞ Monitor for bleeding and hemorrhage. Watch closely for signs and symptoms of intracranial hemorrhage.
• Assess vital signs, temperature, and neurologic status.
• Monitor CBC, blood and urine glucose levels, and liver, kidney, and bone marrow function test results.
• Monitor fluid intake and output.
Patient teaching
☞ Instruct patient to immediately report allergic response, severe abdominal pain, and unusual bleeding or bruising.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to drink plenty of fluids to ensure adequate urine output.
• Tell patient to monitor urine output and report significant changes.
• Instruct patient to avoid activities that can cause injury. Tell him to use soft toothbrush and electric razor to avoid injury to gums and skin.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Tell patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
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