Interactions between tindamax(tinidazole) and 5 fu (fluorouracil)
fluorouracil and tinidazole (Moderate Drug-Drug)
GENERALLY AVOID: Coadministration with a nitroimidazole may increase the toxicity of 5-fluorouracil (5-FU). The interaction has been observed with both metronidazole and misonidazole. The proposed mechanism involves reduced clearance of 5-FU in the presence of nitroimidazoles. In a study of 27 patients with metastatic colorectal cancer who received metronidazole (750 mg/m2 IV) an hour before 5-FU (600 mg/m2 IV) on five consecutive days per week every 4 weeks, an unusually high incidence of fluorouracil toxicity was observed, including granulocytopenia (74%), anemia (41%), stomatitis and oral ulceration (34%), nausea and vomiting (48%), and thrombocytopenia (19%). In another study, 15 patients receiving 5-FU (1 gm/m2) with misonidazole 2 gm/m2 or 3 gm/m2 for advanced colorectal cancer had an increased incidence (44% and 56%, respectively) and severity of nausea and vomiting compared to administration of 5-fluorouracil alone (27%) in a prior course. The incidence of leukopenia was also higher with the combination than 5-FU alone (18% versus 13%), although the difference was not statistically significant. Despite an increase in toxicity, in vitro studies performed by the first group of investigators failed to detect any additive or synergistic antineoplastic effect secondary to the interaction.
MANAGEMENT: Given the potential for increased toxicity, 5-fluorouracil and its prodrugs, capecitabine and tegafur, should probably not be used with nitroimidazoles unless benefits are anticipated to outweigh the risks.
