Thioguanine Disease Interactions

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

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Hepatotoxicity usually presented as hepatic veno-occlusive disease (hyperbilirubinemia, tender hepatomegaly, weight gain due to fluid retention, and ascites) or with signs of portal hypertension (splenomegaly, thrombocytopenia, and esophageal varices), has been reported during therapy with thioguanine. Therapy with thioguanine should be administered cautiously in patients with liver disease or predisposed to it. Patients should be instructed to immediately report any signs of hepatotoxicity such as jaundice, dark urine, upper right quadrant pain, or anorexia. Clinical monitoring of hepatic function and determination of the etiology of hepatic dysfunction is recommended.

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The most consistent, dose-related toxicity of thioguanine is bone marrow suppression. This may be manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. However, any one of these findings may also reflect progression of the underlying disease. Since thioguanine may have a delayed effect, it is important to withdraw the medication temporarily at the first sign of an abnormally large fall in any of the formed elements of the blood. Therapy with thioguanine should be administered cautiously in patients with myelosuppression. It is recommended that evaluation of the hemoglobin concentration or hematocrit, total white blood cell count and differential count, and quantitative platelet count be obtained frequently while the patient is on thioguanine therapy.

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Thioguanine is closely related structurally and functionally to mercaptopurine. A rare deficiency in the enzyme thiopurine methyltransferase (TMPT) results in an increased sensitivity to the myelosuppressive effects of both drugs causing rapid bone marrow suppression following initial mercaptopurine or thioguanine administration. Therapy with thioguanine or mercaptopurine should be administered cautiously and at a reduced dose in patients with TMPT deficiency.

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