PRECAUTIONS General Although the primary toxicity of thioguanine is myelosuppression, other toxicities have occasionally been observed, particularly when thioguanine is used in combination with other cancer chemotherapeutic agents. A few cases of jaundice have been reported in patients with leukemia receiving thioguanine. Among these were 2 adult male patients and 4 pediatric patients with acute myelogenous leukemia and an adult male with acute lymphocytic leukemia who developed hepatic veno-occlusive disease while receiving chemotherapy for their leukemia. Six patients had received cytarabine prior to treatment with thioguanine, and some were receiving other chemotherapy in addition to thioguanine when they became symptomatic. While hepatic veno-occlusive disease has not been reported in patients treated with thioguanine alone, it is recommended that thioguanine be withheld if there is evidence of toxic hepatitis or biliary stasis, and that appropriate clinical and laboratory investigations be initiated to establish the etiology of the hepatic dysfunction. Deterioration in liver function studies during thioguanine therapy should prompt discontinuation of treatment and a search for an explanation of the hepatotoxicity. Administration of live vaccines to immunocompromised patients should be avoided. Information for Patients Patients should be informed that the major toxicities of thioguanine are related to myelosuppression, hepatotoxicity, and gastrointestinal toxicity. Patients should never be allowed to take the drug without medical supervision and should be advised to consult their physician if they experience fever, sore throat, jaundice, nausea, vomiting, signs of local infection, bleeding from any site, or symptoms suggestive of anemia. Women of childbearing potential should be advised to avoid becoming pregnant. Laboratory Tests Consider testing for TPMT and NUDT15 deficiency in patients who experience severe bone marrow toxicities or repeated episodes of myelosuppression. (see WARNINGS). It is advisable to monitor liver function tests (serum transaminases, alkaline phosphatase, bilirubin) at weekly intervals when first beginning therapy and at monthly intervals thereafter. It may be advisable to perform liver function tests more frequently in patients with known pre-existing liver disease or in patients who are receiving thioguanine and other hepatotoxic drugs. Patients should be instructed to discontinue thioguanine immediately if clinical jaundice is detected (see WARNINGS). Drug Interactions There is usually complete cross-resistance between PURINETHOL (mercaptopurine) and TABLOID brand Thioguanine. As there is in vitro evidence that aminosalicylate derivatives (e.g., olsalazine, mesalazine, or sulphasalazine) inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent thioguanine therapy (see WARNINGS). Carcinogenesis, Mutagenesis, Impairment of Fertility In view of its action on cellular DNA, thioguanine is potentially mutagenic and carcinogenic, and consideration should be given to the theoretical risk of carcinogenesis when thioguanine is administered (see WARNINGS). Pregnancy Teratogenic Effects Pregnancy Category D. See WARNINGS section. Nursing Mothers It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for thioguanine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use See DOSAGE AND ADMINISTRATION section. Geriatric Use Clinical studies of thioguanine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general,dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.