Fucil Drug Interactions

Nucleoside Analogues (e.g., Brivudin and Sorivudine): The enzyme dihydropyrimidine dehydrogenase plays an important role in the degradation of 5-FU. Nucleoside analogues can cause a sharp rise in plasma concentrations of 5-FU and other fluoropyrimidines, with accompanying toxic reactions (e.g., severe leukopenia). A period of 4 weeks should elapse between the administration of 5-FU and nucleoside analogues. Where applicable, determination of dihydropyrimidine dehydrogenase enzyme activity is indicated before starting treatment with 5-fluoropyrimidines.
Cimetidine: Pretreatment with cimetidine for 4 weeks may increase plasma concentrations of 5-FU by 27%. The total body clearance was reduced by 28%. This may lead to increased plasma concentrations of 5-FU.
Clozapine: Concomitant administration with 5-FU should be avoided due to the increased risk of agranulocytosis.
Interferon alfa-2b: Concomitant administration with 5-FU has produced a marked increase in the initial plasma concentration of 5-FU and a decrease in 5-FU clearance.
Leucovorin: Leucovorin and 5-FU are routinely used together in the treatment of colorectal cancer due to their synergistic effect. Leucovorin is metabolized to a reduced folate co-factor that is necessary for maximal inhibition of thymidylate synthetase by Fd-UMP, the active metabolite of 5-FU. Leucovorin enhances the DNA-directed toxicity of 5-FU. This combination should be used with caution since leucovorin may exacerbate the GI toxicity of 5-FU.
Levamisole: Combination therapy with 5-FU has been associated with multifocal inflammation leucoencephelopathy (MILE). Symptoms may include memory loss, confusion, paresthesia, muscle weakness, speech disturbances, coma, and seizures. The CSF may show mild pleiocytosis, and computed tomography and magnetic resonance scans may show lesions in the white matter suggestive of demyelination. If this syndrome occurs, treatment should be discontinued immediately. The condition as at least partially reversible if 5-FU and levamisole are discontinued and corticosteroids are given.
Methotrexate: Administration of methotrexate followed by 5-FU leads to a synergistic interaction in the treatment of head and neck, breast and colorectal cancers. Biochemical modulation may occur through effects on RNA and DNA synthesis and enhancement of 5-FU uptake. The importance of time interval between methotrexate and 5-FU exposure in the treatment of metastatic colon cancer has been demonstrated. When these two agents are separated by 24 hours as compared with 1 hour, the response rate, time to progression and survival are significantly improved. However, different tumors may respond differently to changes in the time interval between methotrexate and 5-FU. 5-FU preceded by methotrexate has been demonstrated to double the response rate to 5-FU in metastatic colorectal cancer and produce survival benefits.
Metronidazole: Has been shown to reduce the clearance of 5-FU and increase its toxicity in colorectal cancer patients.
Mitomycin: Hemolytic-uremic syndrome has been reported to occur after long-term use of 5-FU in combination with mitomycin.
Phenytoin: Patients taking phenytoin concomitantly with 5-FU should undergo regular testing because of the possibility of elevated plasma levels of phenytoin resulting in symptoms of phenytoin toxicity.
Sorafenib: Has been reported to have variable effects on 5-FU.
Warfarin: Marked elevations of prothrombin time and INR have been reported in a few patients stabilized on warfarin therapy following initiation of 5-FU regimens.
Laboratory Test Alterations: Increase in or false positive results may be observed in tests for bilirubin (icteric index) and 5-hydroxyindole acetic acid in the urine. 5-FU could interfere with diagnostic tests of thyroid function by causing rises in total thyroxine and liothyronine due to increased globulin binding. Plasma albumin may be decreased because of drug-induced protein malabsorption.