asparaginase


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asparaginase

 [as-par´ah-jin-ās″]
an enzyme that catalyzes removal of the amine group that results in breakdown of asparagine; used as an antineoplastic agent against cancers such as acute lymphoblastic leukemia in which the malignant cells require exogenous asparagine for protein synthesis.

asparaginase

Elspar, Kidrolase (CA)

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.

as·par·a·gi·nase

(as-par'ă-ji-nās),
1. An enzyme catalyzing the hydrolysis of l-asparagine to l-aspartate and ammonia.
2. The enzyme from Escherichia coli, used in the treatment of acute leukemia and other neoplastic diseases.

asparaginase

/as·par·a·gin·ase/ (as-par´ah-jin-ās″) an enzyme that catalyzes the deamination of asparagine; a preparation is used as an antineoplastic agent in acute lymphoblastic leukemia to reduce availability of asparagine to tumor cells.

asparaginase

(ə-spăr′ə-jə-nās′, -nāz′)
n.
An enzyme isolated from bacteria that catalyzes the hydrolysis of asparagine and is used in the chemotherapeutic treatment of acute lymphoblastic leukemia.

asparaginase

(ə-spăr′ə-jə-nās′, -nāz′)
n.
An enzyme isolated from bacteria that catalyzes the hydrolysis of asparagine and is used in the chemotherapeutic treatment of leukemia.

asparaginase

[aspar′əjinās]
Etymology: Gk, asparagos, asparagus
an enzyme that catalyzes the hydrolysis of asparagine to asparaginic acid and ammonia. Asparaginase is used as a chemotherapeutic agent in the treatment of acute lymphoblastic leukemia and lymphosarcoma.

asparaginase

An ENZYME that destroys one of the 20 AMINO ACIDS from which proteins are formed. It is used in the treatment of LEUKAEMIA. The most useful are L-asparaginases which split an amino group from L-asparagine, converting it to aspartic acid. Tumour cells require asparagine which they cannot synthesize as normal cells can. The drug is on the WHO official list.

asparaginase

an enzyme that catalyzes the deamination of asparagine; used as an antineoplastic agent against cancers, e.g. acute lymphocytic leukemia, in which the malignant cells require exogenous asparagine for protein synthesis.
References in periodicals archive ?
Asparaginase has been focused in the search for other microorganisms that produce the enzyme with low toxicity and low-cost raw materials in the fermentation process.
The majority of gram-negative and gram-positive bacteria are asparaginase producers (Huang et al, 2014; Wakil et al, 2015).
A pink zone was observed around the colonies suggesting that endophytic fungi were able to utilize the substrate asparagine by secreting the enzyme asparaginase which catalyzes the breakdown of the substrate (Figure 3).
The pre-treatments included the use of food acids, salts and the enzyme asparaginase.
Asparaginase is the enzyme that hydrolyzes asparagine into L-aspartic acid and ammonia.
Transient, severe hyperlipidemia in patients with acute lymphoblastic leukemia treated with prednisone and asparaginase.
Under the terms of this new legislation, the pioneering asparaginase enzyme solution is authorised as a processing aid in all general food applications in China.
The bulk of the work consists of reviews of the characteristics and uses of the different types of drugs and chemical and biological agents important to the field, including antifolates, cytidine analogues, purine antimetabolites, bleomycin, antitumor antibiotics, asparaginase, bisphosphonates, inhibitors of tumor angiogenesis, interferons, and interleukins, to cite a few.
Chemotherapy with decadron, vincristine, daunomycin, cyclophosphamide, asparaginase, and intrathecal was begun.