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Drug Interactions between metronidazole and Prograf

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

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Interactions between your drugs

Moderate

metroNIDAZOLE tacrolimus

Applies to: metronidazole and Prograf (tacrolimus)

MONITOR: Coadministration with a nitroimidazole may increase the blood concentrations of tacrolimus. The interaction has been reported with metronidazole, and the proposed mechanism is inhibition of hepatic tacrolimus metabolism via CYP450 3A4. In one case report, the tacrolimus levels of a kidney transplant patient increased 100% nine days after the addition of metronidazole (400 mg three times a day). His serum creatinine level was also increased. Both tacrolimus and creatinine levels declined following a decrease in the dosage of tacrolimus by more than 50%. After completion of the 2-week course of metronidazole, tacrolimus levels became subtherapeutic and an increase in the tacrolimus dosage was necessary. No data are available for tinidazole.

MANAGEMENT: Caution is advised if tacrolimus is used with metronidazole. Tacrolimus blood levels and renal function should be checked frequently and the dosage adjusted accordingly, particularly following initiation or discontinuation of metronidazole therapy in patients who are stabilized on their tacrolimus regimen. Given its structural similarities to metronidazole, the same precaution may be applicable during therapy with tinidazole, although clinical data are lacking.

References

  1. (2001) "Product Information. Flagyl (metronidazole)." Searle
  2. Herzig K, Johnson DW (1999) "Marked elevation of blood cyclosporine and tacrolimus levels due to concurrent metronidazole therapy." Nephrol Dial Transplant, 14, p. 521-3
  3. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
  4. Page RL, Klem PM, Rogers C (2005) "Potential elevation of tacrolimus trough concentrations with concomitant metronidazole therapy." Ann Pharmacother, 39, p. 1109-13
View all 4 references

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Drug and food interactions

Major

metroNIDAZOLE food

Applies to: 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 (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. (2001) "Product Information. Flagyl (metronidazole)." Searle
  5. Edwards DL, Fink PC, Van Dyke PO (1986) "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm, 5, p. 999-1000
  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. (2017) "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc
View all 9 references

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Moderate

tacrolimus food

Applies to: Prograf (tacrolimus)

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References

  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11

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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.

See also

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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.

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