oguanine.
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.
Adverse Reactions
The most frequent adverse reaction to Thioguanine is myelosuppression. The induction of complete remission of acute myelogenous leukemia usually requires combination chemotherapy in dosages which produce marrow hypoplasia. Since consolidation and maintenance of remission are also effected by multiple-drug regimens whose component agents cause myelosuppression, pancytopenia is observed in nearly all patients. Dosages and schedules must be adjusted to prevent life-threatening cytopenias whenever these adverse reactions are observed.
Hyperuricemia frequently occurs in patients receiving Thioguanine as a consequence of rapid cell lysis accompanying the antineoplastic effect. Adverse effects can be minimized by increased hydration, urine alkalinization, and the prophylactic administration of a xanthine oxidase inhibitor such as ZYLOPRIM® (allopurinol). Unlike PURINETHOL (mercaptopurine) and IMURAN® (azathioprine), Thioguanine may be continued in the usual dosage when allopurinol is used conjointly to inhibit uric acid formation.
Less frequent adverse reactions include nausea, vomiting, anorexia, and stomatitis. Intestinal necrosis and perforation have been reported in patients who received multiple-drug chemotherapy including Thioguanine.
Hepatic Effects
Liver toxicity associated with vascular endothelial damage has been reported when Thioguanine is used in maintenance or similar long-term continuous therapy which is not recommended (see WARNINGS and DOSAGE AND ADMINISTRATION). This usually presents as the clinical syndrome of hepatic veno-occlusive disease (hyperbilirubinemia, tender hepatomegaly, weight gain due to fluid retention, and ascites) or signs and symptoms of portal hypertension (splenomegaly, thrombocytopenia, and esophageal varices). Elevation of liver transaminases, alkaline phosphatase, and gamma glutamyl transferase an |
