Drug interactions between lamivudine and Tabloid

MONITOR: The concomitant or sequential use of other agents known to induce hepatotoxicity may potentiate the risk of liver injury associated with thioguanine. A high risk of liver toxicity characterized by vascular endothelial damage has been reported with long-term continuous use of thioguanine, particularly in children receiving the drug as part of maintenance therapy for acute lymphoblastic leukemia and in other conditions associated with continuous use. Liver toxicity usually presents as the clinical syndrome of 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). Histopathological features include hepatoportal sclerosis, nodular regenerative hyperplasia, peliosis hepatitis, and periportal fibrosis.

MANAGEMENT: The use of thioguanine in combination with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; endothelin receptor antagonists; interferons; nucleoside reverse transcriptase inhibitors; thiazolidinediones; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, HMG-CoA reductase inhibitors, and niacin; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice) should be approached with caution. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Baseline and regular monitoring of hepatic function is recommended. Thioguanine therapy should be discontinued if there is evidence of toxic hepatitis or biliary stasis, as reversal of signs and symptoms of liver toxicity have been reported upon withdrawal. Early indications of liver toxicity are signs associated with portal hypertension such as thrombocytopenia out of proportion with neutropenia and splenomegaly. Elevations of liver enzymes have also been reported but do not always occur.