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Drug Interactions between Fasigyn and Xeloda

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

capecitabine tinidazole

Applies to: Xeloda (capecitabine) and Fasigyn (tinidazole)

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.

References

  1. (2001) "Product Information. Flagyl (metronidazole)." Searle
  2. Bardakji Z, Jolivet J, Langelier Y, et al. (1986) "5-fluorouracil-metronidazole combination therapy in metastatic colorectal cancer." Cancer Chemother Pharmacol, 18, p. 140-4
  3. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
  4. Spooner D, Bugden RD, Peckham MJ, Wist EA (1982) "The combination of 5-fluorouracil with misonidazole in patients with advanced colon cancer." Int J Radiat Oncol Biol Phys, 8, p. 387-9
View all 4 references

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Drug and food interactions

Moderate

tinidazole food

Applies to: Fasigyn (tinidazole)

GENERALLY AVOID: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for up to 3 days after completion of systemic nitroimidazole therapy.

References

  1. Giannini AJ, DeFrance DT (1983) "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol, 20, p. 509-15
  2. Alexander I (1985) "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract, 39, p. 292-3
  3. Harries DP, Teale KF, Sunderland G (1990) "Metronidazole and alcohol: potential problems." Scott Med J, 35, p. 179-80
  4. Edwards DL, Fink PC, Van Dyke PO (1986) "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm, 5, p. 999-1000
  5. (2002) "Product Information. Flagyl (metronidazole)." Searle
  6. Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
  8. Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
  9. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
View all 9 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.