Thioguanine Side Effects, and Drug Interactions - Thioguanine

Thioguanine Side Effects, and Drug Interactions - Thioguanine

SIDE EFFECTS

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 enzyme and other liver function studies are occasionally abnormal. If jaundice, hepatomegaly, or anorexia with tenderness in the right hypochondrium occurs, thioguanine should be withheld until the exact etiology can be determined. There have been reports of veno-occlusive liver disease occurring in patients who received combination chemotherapy including thioguanine. Esophageal varices have been reported in patients receiving continuous busulfan and thioguanine therapy for treatment of chronic myelogenous leukemia (see PRECAUTIONS: Drug Interactions).

There is usually complete cross-resistance between PURINETHOL (mercaptopurine) and TABLOID brand Thioguanine.

In one study, 12 of approximately 330 patients receiving continuous busulfan and thioguanine therapy for treatment of chronic myelogenous leukemia were found to have esophageal varices associated with abnormal liver function tests. Subsequent liver biopsies were performed in 4 of these patients, all of which showed evidence of nodular regenerative hyperplasia. Duration of combination therapy prior to the appearance of esophageal varices ranged from 6 to 45 months. With the present analysis of the data, no cases of hepatotoxicity have appeared in the busulfan-alone arm of the study. Long-term continuous therapy with thioguanine and busulfan should be used with caution.

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).