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(THIGH-oh-GWAHN-een)
Class: Purine antimetabolite

 Actions Thioguanine, an analog of the nucleic acid constituent guanine, is closely related structurally and functionally to 6-mercaptopurine. Thioguanine nucleotides are incorporated into RNA and DNA by phosphodiester linkages and incorporation of such fraudulent bases may contribute to the cytotoxicity of thioguanine. Oral absorption averages 30%. IV administration disclosed a median plasma half-life of 80 min (25 to 240 min) when the compound was given in single doses of 65 to 300 mg/m2. Trace quantities of parent drug are excreted in the urine.

 Indications

Adult/Pediatric

Acute nonlymphocytic leukemia.

Chronic myelogenous leukemia.

 Contraindications Prior resistance to this drug. There is usually complete cross-resistance between mercaptopurine and thioguanine.

 Route/Dosage

Acute Nonlymphocytic Leukemia, Remission Induction, Single Agent Therapy

ADULTS: PO 2 mg/kg/day, rounded to nearest 20 mg, as a single daily dose. If no clinical improvement in 4 wk, may slowly increase the dose to 3 mg/kg/day.

PEDIATRIC: Children ³ 3 years of age: PO 2 mg/kg/day, rounded to nearest 20 mg, as a single daily dose. If no clinical improvement in 4 wk, may slowly increase the dose to 3 mg/kg/day.

Acute Nonlymphocytic Leukemia, Remission Induction, Combination Therapy

ADULTS: PO 75 to 200 mg/m2/day, rounded to the nearest 20 mg, in 1 or 2 divided doses for 5 to 7 days in each course of therapy until remission occurs.

Acute Nonlymphocytic Leukemia, Maintenance Therapy

ADULTS: PO 2 mg/kg/day, rounded to the nearest 20 mg. Alternatively, 75 to 400 mg/m2/day PO, titrated to response.

Acute Nonlymphocytic Leukemia, Induction, Combination Therapy

PEDIATRIC: Infants and children < 3 years of age: PO 3.3 mg/kg/day in 2 divided doses for 4 days in each course of therapy until remission occurs.

Acute Leukemia, Remission Induction, Combination Therapy

PEDIATRIC: Children ³ 3 years of age: PO 75 to 200 mg/m2/day, rounded to the nearest 20 mg, in 1 or 2 divided doses for 5 to 7 days in each course of therapy until remission occurs.

Maintenance Therapy

PEDIATRIC: Children ³ 3 years of age: PO 2 mg/kg/day, rounded to the nearest 20 mg. Alternatively, 50 mg/m2/day, titrated to response.

Interactions

Bisulfan

Concomitant therapy may increase risk of hepatotoxicity, esophageal varices, and portal hypertension.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Ataxia, loss of vibration sensation. GI: Anorexia, mucositis, diarrhea, elevated LFTs, jaundice, veno-occlusive disease. HEMATOLOGIC: Bone marrow suppression, nadir at 2 to 4 wk.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Adjustment in renal or hepatic insufficiency (adult): Dosage reduction is advised in patients with impaired renal or hepatic function. Specific recommendations are currently unavailable. Bone marrow suppression: May be manifested by anemia, leukopenia, or thrombocytopenia. Dosage adjustment (pediatric): Follow dosage adjustment guidelines recommended for adults. Hepatotoxicity: Jaundice has occurred. Withhold thioguanine if there is evidence of toxic hepatitis, biliary stasis, clinical jaundice, hepatomegaly, or anorexia with tenderness in the right hypochondrium.

PATIENT CARE CONSIDERATIONS

 Administration/Storage

  • Store at room temperature in a dry place. The extemporaneous suspension is stable for 84 days stored at room temperature in amber glass bottles.
  • Administer PO. Give on an empty stomach to facilitate absorption.
  • Follow procedures for proper handling and disposal of anticancer drugs. Wear gloves and avoid skin exposure and inhalation of fumes.

Extemporaneous oral suspension (40 mg/mL)

  • Crush fifteen 40 mg oral tablets completely and suspend in sufficient Cologel suspending agent for a total volume of 5 mL. Dilute with a 2:1 mixture of simple syrup and cherry syrup for a final total volume of 15 mL. Shake the suspension well before using.

 Assessment/Interventions

  • Monitor CBC at least once weekly during therapy.
  • Monitor serum transaminase, alkaline phosphatase, and bilirubin weekly when initiating therapy; may monitor once monthly later in therapy course.
  • Hyperuricemia may occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.
OVERDOSAGE: SIGNS & SYMPTOMS
  Nausea, vomiting, malaise, hypertension, diaphoresis, myelosuppression, azotemia

 Patient/Family Education

  • Notify health care provider if fever, chills, nausea, vomiting, sore throat, unusual bleeding or bruising, yellow discoloration of the skin or eyes, swelling of the feet or legs, abdominal pain, or joint or flank pain occurs.
  • May cause diarrhea, fever, and weakness. Notify health care provider if these become pronounced.
  • Drink plenty of liquids while taking this drug.
  • Contraceptive measures are recommended during therapy for men and women.

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