otential mutagens and teratogens. Thioguanine may cause fetal harm when administered to a pregnant woman. Thioguanine has been shown to be teratogenic in rats when given in doses 5 times the human dose. When given to the rat on the 4th and 5th days of gestation, 13% of surviving placentas did not contain fetuses, and 19% of offspring were malformed or stunted. The malformations noted included generalized edema, cranial defects, and general skeletal hypoplasia, hydrocephalus, ventral hernia, situs inversus, and incomplete development of the limbs. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
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
Prescribers should be aware that some laboratories offer testing for TPMT deficiency (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 Thi |
