Fluorouracil Metronidazole

FLUOROURACIL ANTIBIOTICS -METRONIDAZOLE t risk of toxic effects of fluorouracil (>27%), e.g. bone marrow suppression, oral ulceration, nausea and vomiting due to T plasma concentrations of fluorouracil Metronidazole i clearance of fluorouracil Avoid co-administration... 

Bardakji Z, Jolivet J, Langelier Y, Besner JG, Ayoub J. 5-Fluorouracil-metronidazole combination therapy in metastatic colorectal cancer. Clinical, pharmacokinetic and in vitro cytotoxicity studies. Cancer Chemother Pharmacol 1986 18(2) 140. ... 

Fig. 5.20 Imidazoles (A-F) A, metronidazole B, clotrimazole C, miconazole D, econazole E, ketoconazole F, fluconazole G, flucytosine H, 5-fluorouracil I, terbinafme J, tolnaftate.

Chloral hydrate Chloramphenicol Cimetidine Ciprofloxacin Clofibrate Danazol Disulfiram Doxycycline Erythromycin Fenofibrate Fluconazole Fluorouracil Fluoxetine Fluvoxamine Gemfibrozil Influenza vaccine Isoniazid Itraconazole Fovastatin Metronidazole Miconazole Moxalactam Neomycin Norfloxacin Ofloxacin Omeprazole Phenylbutazone Piroxicam Propafenone Propoyxphene Quinidine Sertraline Sulfamethoxazole Sulfinpyrazone Tamoxifen Testosterone Vitamin E Zafirlukast... 

The following drug interactions were reported for metronidazole, a chemically related nitroimidazole. Therefore, these drug interactions may occur with tinidazole. Drugs that may affect tinidazole include cholestyramine, CYP3A4 inducers and inhibitors and oxytetracycline. Drugs that may be affected by tinidazole include alcohols, anticoagulants, cyclosporine, tacrolimus, disulfiram, fluorouracil, hydantoins, and lithium. 

Pretreatment with metronidazole increased the toxicity of fluorouracil given by daily bolus dose (148). The chnical significance of this is yet to be determined. 

A marked increase in fluorouracil toxicity was noted in 27 patients with metastatic colorectal cancer when they were given intravenous metronidazole 750 mg/m one hour before reeeiving intravenous fluorouracil 600 mg/m 5 days per week, every 4 weeks. Granuloeytopenia occurred in 74% of patients, nausea and vomiting in 48%, anaemia in 41%, stomatitis and oral ulceration in 34%, and thrombocytopenia in 19%. A pharmacokinetic study in 10 patients found that metronidazole reduced the clearance of fluorouracil by 27% over the 5-day period and increased the AUC by 34%. In vitro studies with human colon cancer cells failed to show any increased efficacy. ... 

Metronidazole reduces the clearance of fluorouracil, thereby increasing its toxic effects. 

Information is limited but the interaction between fluorouracil and metronidazole appears to be established. It was hoped that metronidazole or mi-sonidazole (no longer in clinical use) might increase the efficacy of fluorouracil. However, the studies above show that the toxicity of fluorouracil is increased without an obvious increase in its therapeutic efficacy. Care should be taken if metronidazole is required for its anhmicrobial effects in a patient receiving fluorouracil. Whether other nitroimidazoles (e.g. tinidazole) behave similarly appears not to have been studied. 

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