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Drug Interactions between busulfan and Flagyl

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

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Interactions between your drugs

Major

metroNIDAZOLE busulfan

Applies to: Flagyl (metronidazole) and busulfan

GENERALLY AVOID: Coadministration with metronidazole may significantly increase the plasma concentrations of busulfan. The mechanism of interaction has not been described. In a group of patients receiving myeloablative therapy with busulfan (1 mg/kg orally for 4 days) prior to undergoing hematopoietic stem cell transplantation, five patients who were coadministered metronidazole (400 mg orally three times daily for 4 days) had an 87% increase in mean busulfan trough concentrations compared to ten patients who were administered busulfan alone. In nine patients who received metronidazole only for the last 2 days of busulfan administration, busulfan concentrations increased 79% compared to the first 2 days. In patients who received busulfan and metronidazole concomitantly for 4 days, all experienced elevated liver transaminases (AST, ALT) and bilirubin. Three patients also experienced veno-occlusive disease (one died with multi-organ failure), while one developed hemorrhagic cystitis. In the group who received metronidazole only on the last two days of busulfan therapy, six had elevated liver function tests, but no veno-occlusive disease was observed.

MANAGEMENT: Due to the potential for severe toxicity and mortality associated with elevated busulfan plasma levels, concomitant use with metronidazole should be avoided. However, if concomitant therapy is necessary, close monitoring for signs of busulfan toxicity is recommended.

References

  1. Nilsson C, Aschan J, Hentschke P, Ringden O, Ljungman P, Hassan M "The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation." Bone Marrow Transplant 31 (2003): 429-435
  2. "Product Information. Busulfex (busulfan)." ESP Pharma Inc (2004):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Gulbis AM, Culotta KS, Jones RB, Andersson BS "Busulfan and metronidazole: an often forgotten but significant drug interaction." Ann Pharmacother 45 (2011): e39
View all 4 references

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Drug and food interactions

Major

metroNIDAZOLE food

Applies to: Flagyl (metronidazole)

CONTRAINDICATED: 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. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

References

  1. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  2. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  3. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  4. "Product Information. Flagyl (metronidazole)." Searle PROD (2001):
  5. Edwards DL, Fink PC, Van Dyke PO "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm 5 (1986): 999-1000
  6. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4
  8. Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8
  9. "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc (2017):
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.