Metronidazole interactions

Food & lifestyle

• alcohol

  Major

  Metabolism

  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'.

  What to do: 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.

  9 sources

  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 (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

  Show all 9 sourcesShow fewer sources

  9. "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc (2017):

Conditions

Conditions in which Metronidazole needs care, as documented in this source.

• Colitis

  Major

  Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

  31 sources

  1. "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories (2002):
  2. "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome (2002):
  3. "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome (2002):
  4. "Product Information. Cleocin (clindamycin)." Pharmacia and Upjohn (2002):
  5. "Product Information. Macrobid (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  6. "Product Information. Macrodantin (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  7. "Product Information. Amoxil (amoxicillin)." SmithKline Beecham (2001):
  8. "Product Information. Merrem (meropenem)." Astra-Zeneca Pharmaceuticals (2001):

  Show all 31 sourcesShow fewer sources

  9. "Product Information. Coly-Mycin M Parenteral (colistimethate)." Parke-Davis (2001):
  10. "Product Information. Lincocin (lincomycin)." Pharmacia and Upjohn (2001):
  11. "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc (2003):
  12. "Product Information. Xifaxan (rifaximin)." Salix Pharmaceuticals (2004):
  13. "Product Information. Doribax (doripenem)." Ortho McNeil Pharmaceutical (2007):
  14. "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc (2009):
  15. "Product Information. Vibativ (telavancin)." Theravance Inc (2009):
  16. "Product Information. Teflaro (ceftaroline)." Forest Pharmaceuticals (2010):
  17. "Product Information. Penicillin G Sodium (penicillin G sodium)." Sandoz Inc (2022):
  18. "Product Information. Dalvance (dalbavancin)." Durata Therapeutics, Inc. (2014):
  19. "Product Information. Orbactiv (oritavancin)." The Medicines Company (2014):
  20. "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions (2017):
  21. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
  22. "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC (2022):
  23. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  24. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  25. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
  26. "Product Information. Aemcolo (rifamycin)." Aries Pharmaceuticals, Inc. (2018):
  27. "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc (2019):
  28. "Product Information. Biaxin (clarithromycin)." AbbVie US LLC (2019):
  29. "Product Information. Zithromax (azithromycin)." Pfizer U.S. Pharmaceuticals Group (2021):
  30. "Product Information. E.E.S.-400 Filmtab (erythromycin)." Arbor Pharmaceuticals (2018):
  31. "Product Information. Priftin (rifapentine)." sanofi-aventis (2020):

• Hematologic Diseases

  Major

  The use of nitroimidazoles (e.g., metronidazole, tinidazole) has rarely been associated with hematologic adverse effects such as mild, transient leukopenia, thrombocytopenia, and bone marrow aplasia. The manufacturers recommend that therapy with nitroimidazoles be administered cautiously in patients with evidence of or a history of blood dyscrasias, and that total and differential leukocyte counts be performed before and after treatment with these drugs, particularly in patients receiving repeated courses of therapy.

  4 sources

  1. Smith JA "Neutropenia associated with metronidazole therapy." Can Med Assoc J 123 (1980): 202
  2. White CM, Price JJ, Hunt KM "Bone marrow aplasia associated with metronidazole." Br Med J 280 (1980): 647
  3. "Product Information. Flagyl (metronidazole)." Searle (2002):
  4. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):

• Neurotoxicity Syndromes

  Major

  The use of nitroimidazoles (e.g., metronidazole, tinidazole) has been associated with the development of nervous system toxicity including convulsive seizures and dose-related peripheral neuropathy, the latter characterized primarily by numbness or paresthesia of an extremity. Persistent peripheral neuropathy has been reported in some patients treated for prolonged periods. Other neurologic adverse effects include vertigo, incoordination, ataxia, confusion, agitation, hallucinations, and depression. Therapy with nitroimidazoles should be administered cautiously in patients with or predisposed to seizures or other nervous system abnormalities. Nitroimidazole therapy should be discontinued promptly if neurologic disturbances occur.

  14 sources

  1. Kusumi RK, Plouffe JF, Wyatt RH, Fass RJ "Central nervous sytem toxicity associated with metronidazole therapy." Ann Intern Med 93 (1980): 59-60
  2. Schentag JJ, Ziemniak JA, Greco JM, Rainstein M, Buckley RJ "Mental confusion in a patient treated with metronidazole: a concentration-related effect." Pharmacotherapy 2 (1982): 384-7
  3. Alvarez RS, Richardson DA, Bent AE, Ostergard DR "Central nervous system toxicity related to prolonged metronidazole therapy." Am J Obstet Gynecol 145 (1983): 640-1
  4. Wienbren M, Perinpanayagam RM, Camba L, Lee CA "Convulsions and encephalopathy in a patient with leukaemia after treatment with metronidazole." J Clin Pathol 38 (1985): 1076
  5. Duffy LF, Daum F, Fisher SE, et al. "Peripheral neuropathy in Crohn's disease patients treated with metronidazole." Gastroenterology 88 (1985): 681-4
  6. Boyce EG, Cookson ET, Bond WS "Persistent metronidazole-induced peripheral neuropathy." DICP 24 (1990): 19-21
  7. Stahlberg D, Barany F, Einarsson K, Ursing B, Elmquist D, Persson A "Neurophysiologic studies of patients with Crohn's disease on long-term treatment with metronidazole." Scand J Gastroenterol 26 (1991): 219-24
  8. "Product Information. Flagyl (metronidazole)." Searle (2002):

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  9. Learned-Coughlin S "Peripheral neuropathy induced by metronidazole." Ann Pharmacother 28 (1994): 536
  10. Lawford R, Sorrell TC "Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report." Clin Infect Dis 19 (1994): 346-8
  11. Ahmed A, Laes DJ, Bressler EL "Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy." Neurology 45 (1995): 588-9
  12. Schreiber W, Spernal J "Metronidazole-induced psychotic disorder." Am J Psychiatry 154 (1997): 1170-1
  13. Beloosesky Y, Grosman B, Marmelstein V, Grinblat J "Convulsions induced by metronidazole treatment for Clostridium difficile-associated disease in chronic renal failure." Am J Med Sci 319 (2000): 338-9
  14. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):

• Alcoholism

  Moderate

  Nitroimidazoles (e.g., metronidazole, tinidazole, fexinidazole, secnidazole) may inhibit alcohol dehydrogenase and occasionally precipitate a disulfiram-like reaction in patients who consume alcohol while being treated. Symptoms may include abdominal cramps, nausea, vomiting, headache, flushing, rash, weakness, diarrhea, abdominal pain, dizziness, sweating, and hypotension. Patients should be instructed to avoid alcohol-containing products during nitroimidazole therapy and for at least 48 hours (fexinidazole, secnidazole) to 72 hours (metronidazole, tinidazole) after the last dose. Therapy with nitroimidazoles should be administered cautiously in patients who might be prone to acute alcohol intake. An alternative therapy may be appropriate.

  4 sources

  1. "Product Information. Flagyl (metronidazole)." Searle (2002):
  2. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):
  3. "Product Information. Solosec (secnidazole)." Symbiomix Therapeutics (2017):
  4. "Product Information. Fexinidazole (fexinidazole)." sanofi-aventis (2021):

• Diseases requiring dialysis

  Moderate

  Metronidazole and its metabolites are moderately removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

  5 sources

  1. Somogyi A, Kong C, Sabto J, Gurr FW, Spicer WJ, McLean AJ "Disposition and removal of metronidazole in patients undergoing haemodialysis." Eur J Clin Pharmacol 25 (1983): 683-7
  2. Roux AF, Moirot E, Delhotal B, et al. "Metronidazole kinetics in patients with acute renal failure on dialysis: a cumulative study." Clin Pharmacol Ther 36 (1984): 363-8
  3. Kreeft JH, Ogilvie RI, Dufresne LR "Metronidazole kinetics in dialysis patients." Surgery 93 (1983): 149-53
  4. Lau AH, Chang CW, Sabatini S "Hemodialysis clearance of metronidazole and its metabolites." Antimicrob Agents Chemother 29 (1986): 235-8
  5. "Product Information. Flagyl (metronidazole)." Searle (2002):

• Heart Failure

  Moderate

  Flagyl I.V. RTU (brand of metronidazole ready-to-use injection) contains 14 mEq of sodium per each 500 mg dose of metronidazole. The sodium content should be considered when this product is used in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

  1 source

  1. "Product Information. Flagyl (metronidazole)." Searle (2002):

• Liver Diseases

  Moderate

  Metronidazole is extensively metabolized by the liver to both pharmacologically active and inactive compounds. The plasma clearance of metronidazole may be decreased and the half-life prolonged in patients with impaired hepatic function. Therapy with metronidazole should be administered cautiously at reduced dosages in patients with severe liver disease.

  6 sources

  1. Lau AH, Evans R, Chang CW, Seligsohn R "Pharmacokinetics of metronidazole in patients with alcoholic liver disease." Antimicrob Agents Chemother 31 (1987): 1662-4
  2. Jensen JC, Gugler R "Single- and multiple-dose metronidazole kinetics." Clin Pharmacol Ther 34 (1983): 481-7
  3. Farrell G, Baird-Lambert J, Cvejic M, Buchanan N "Disposition and metabolism of metronidazole in patients with liver failure." Hepatology 4 (1984): 772-6
  4. Loft S, Dossing M, Poulsen HE, et al. "Influence of dose and route of administration on disposition of metronidazole and its major metabolites." Eur J Clin Pharmacol 30 (1986): 467-73
  5. Loft S, Sonne J, Dossing M, Andreasen PB "Metronidazole pharmacokinetics in patients with hepatic encephalopathy." Scand J Gastroenterol 22 (1987): 117-23
  6. "Product Information. Flagyl (metronidazole)." Searle (2002):