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Action/Kinetics:
Purine antagonist that is cell-cycle specific for the S phase of cell division. Converted to 6-thioguanylic acid, which in turn interferes with the synthesis of guanine nucleotides by competing with hypoxanthine and xanthine for the enzyme phosphoribosyltransferase (HGPRTase). Ultimately the synthesis of RNA and DNA is inhibited. Resistance to the drug may result from increased breakdown of 6-thioguanylic acid or loss of HGPRTase activity. Partially absorbed (30%) from GI tract.
t
1/2: 80 min. Detoxified by liver and excreted in the urine. More effective in children than in adults. Cross-resistance with mercaptopurine. Perform platelet counts weekly; discontinue drug if abnormally large fall in blood count is noted, indicating severe bone marrow depression.
Uses:
Acute and nonlymphocytic leukemias (usually in combination with other drugs such as cyclophosphamide, cytarabine, prednisone, vincristine). Chronic myelogenous leukemia (not first-line therapy).
Contraindications:
Resistance to mercaptopurine or thioguanine. Lactation.
Additional Side Effects:
Loss of vibration sense, unsteadiness of gait.
Hepatotoxicity myelosuppression (common), hyperuricemia. Adults tend to show a more rapid fall in WBC count than children.
Laboratory Test Alterations:
Uric acid in blood and urine.
Overdose Management:
Symptoms: N&V;, hypertension, malaise, and diaphoresis may be seen immediately, which may be followed by myelosuppression and azotemia.
Severe hematologic toxicity.
Treatment: Induce vomiting if client is seen immediately after an acute overdosage. Treat symptoms. Hematologic toxicity may be treated by platelet transfusions (for bleeding) and granulocyte transfusions. Antibiotics are indicated for sepsis.
How Supplied:
Tablet: 40 mg
Dosage
?Tablets
Individualized and determined by hematopoietic response.
Adults and pediatric, initial: 2 mg/kg/day (or 75-100 mg/m
2) given at one time. From 2 to 4 weeks may elapse before beneficial results become apparent. Compute dose to nearest multiple of 20 mg. If no response, dosage may be increased to 3 mg/kg/day.
Usual maintenance dose (even during remissions): 2-3 mg/kg/day (or 100 mg/m
2). Dosage of thioguanine does not have to be decreased during administration of allopurinol (to inhibit uric acid production).
