Thioguanine

Trade Names:Tabloid- Tablets 40 mg

Pharmacology

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.

Pharmacokinetics

Absorption

Thioguanine absorption is incomplete and variable, averaging about 30%. T _max is 8 h and C _max is seldom over 1 to 2 mcg/mL.

Metabolism

Thioguanine undergoes rapid metabolism to active intracellular derivatives.

Elimination

Trace quantities of thioguanine are found in urine; some metabolites are found in urine after about 22 h.

Indications and Usage

For remission induction and remission consolidation therapy of acute nonlymphocytic leukemia; busulfan is the preferred drug for treating the chronic phase of chronic myelogenous leukemia.

Unlabeled Uses

Psoriasis; second-line treatment of ulcerative colitis; Crohn disease.

Contraindications

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

Dosage and Administration

PO 2 mg/kg/day; if there is no clinical improvement and no leukocyte or platelet depression, the dosage may be cautiously increased to 3 mg/kg/day.

General Advice

• Follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs.
• Administer total daily dose at one time.

Storage/Stability

Store tablets at controlled room temperature (59° to 77°F). Protect from moisture.

Drug Interactions

Based on in vitro data, which indicates enzyme inhibition by aminosalicylate derivatives, use with caution.

There is usually complete cross-resistance between mercaptopurine and thioguanine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

GI

Anorexia; intestinal necrosis and perforation (with multiple-drug regimens); nausea; stomatitis; vomiting.

Genitourinary

Hyperuricemia.

Hematologic-Lymphatic

Myelosuppression; pancytopenia (with multiple-drug regimens).

Hepatic

Abnormal liver enzymes; jaundice; liver toxicity associated with vascular endothelial damage (hepatic veno-occlusive disease and/or signs and symptoms of portal hypertension).

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Elderly

Dose selection should be cautious, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function, and comorbidity.

Bone marrow suppression

Most consistent, dose-related toxicity; may be manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. Withdraw thioguanine temporarily at first sign of an abnormally large fall in any of the formed elements of the blood.

Enzyme deficiency

There are patients with inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effects of thioguanine and prone to developing rapid bone marrow suppression following initiation of treatment. Substantial dosage reductions may be required to avoid life-threatening bone marrow suppression.

Hepatotoxicity

Has occurred. Discontinue in patients with evidence of liver toxicity.

Hyperuricemia

Frequently occurs; ensure risk of developing hyperuricemia is evaluated before starting therapy and that hypouricemic therapy, including adequate fluid intake and monitoring of uric acid, is initiated before starting treatment in patient determined to be at risk for developing hyperuricemia and urate precipitation.

Live vaccines

Do not administer live vaccines to immunocompromised patients.

Maintenance

Not recommended for maintenance therapy or similar long-term continuous treatments because of the risk of liver toxicity.

Overdosage

Symptoms

Azotemia, diaphoresis, hypotension, malaise, myelosuppression, nausea, vomiting.

Patient Information

• Advise patient, family, or caregiver that medication may be used in combination with other agents, to achieve maximum benefit possible.
• Advise patient to take as a single daily dose.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; fever, chills or other signs of infection; bleeding or unusual bruising; sores in mouth or sore throat; persistent nausea, vomiting, and/or appetite loss; dark urine; yellowing of skin or eyes; paleness; general body weakness.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.

Copyright © 2009 Wolters Kluwer Health.