asparaginase
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asparaginase
[as-par´ah-jin-ās″]asparaginase
Pharmacologic class: Enzyme
Therapeutic class: Antineoplastic (miscellaneous)
Pregnancy risk category C
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.
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.