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Drug Interactions between black cohosh and metronidazole topical

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

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Interactions between your drugs

Moderate

metroNIDAZOLE topical black cohosh

Applies to: metronidazole topical and black cohosh

GENERALLY AVOID: Due to a potentially high alcohol content, tincture formulations of black cohosh may produce a disulfiram-like reaction when coadministered with drugs that can inhibit aldehyde dehydrogenase (ALDH) such as nitroimidazoles (e.g., metronidazole, tinidazole), nitrofurans (e.g., furazolidone, nifurtimox), and cephalosporins with an N-methylthiotetrazole (NMTT) side chain that structurally resembles 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. The interaction is well established for disulfiram. However, data for other potential ALDH inhibitors such as metronidazole and cephalosporins are limited and conflicting.

MANAGEMENT: Until more information is available, the use of black cohosh tinctures with nitroimidazoles (including vaginal formulations), nitrofurans, and certain cephalosporins should be avoided if possible.

References

  1. Uri JV, Parks DB (1983) "Disulfiram-like reaction to certain cephalosporins." Ther Drug Monit, 5, p. 219-24
  2. Kline SS, Mauro VF, Forney RB Jr, et al. (1987) "Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia." Antimicrob Agents Chemother, 31, p. 1328-31
  3. Portier H, Chalopin JM, Freysz M, Tanter Y (1980) "Interaction between cephalosporins and alcohol." Lancet, 08/02/80, p. 263
  4. Shimada J, Hayashi Y, Nakamura K (1985) "Cefmetazole: clinical evaluation of efficacy and safety in Japan." Drugs Exp Clin Res, 11, p. 181-94
  5. Freundt KJ, Kitson TM (1986) "Inactivation of aldehyde dehydrogenase by a putative metabolite of cefamandole." Infection, 14, p. 44-7
  6. Freundt KJ, Schreiner E, Christmann-Kleiss U (1985) "Cefamandole: a competitive inhibitor of aldehyde dehydrogenase." Infection, 13, p. 91
  7. McMahon FG (1980) "Disulfiram-like reaction to a cephalosporin." JAMA, 243, p. 2397
  8. Reeves DS, Davies AJ (1980) "Antabuse effect with cephalosporins." Lancet, 2, p. 540
  9. Giannini AJ, DeFrance DT (1983) "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol, 20, p. 509-15
  10. Alexander I (1985) "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract, 39, p. 292-3
  11. Harries DP, Teale KF, Sunderland G (1990) "Metronidazole and alcohol: potential problems." Scott Med J, 35, p. 179-80
  12. Neu HC, Prince AS (1980) "Interaction between moxalactam and alcohol." Lancet, June, p. 1422
  13. Brown KR, Guglielmo BJ, Pons VG, Jacobs RA (1982) "Theophylline elixir, moxalactam, and a disulfiram reaction." Ann Intern Med, 97, p. 621-2
  14. Umeda S, Arai T (1985) "Disulfiram-like reaction to moxalactam after celiac plexus alcohol block." Anesth Analg, 64, p. 377
  15. (2001) "Product Information. Flagyl (metronidazole)." Searle
  16. Jones RO (1949) "Death following the ingestion of alcohol in an antabuse treated patient." Can Med Assoc J, 60, p. 609-12
  17. Stoll D, King LE (1980) "Disulfiram-alcohol skin reaction to beer-containing shampoo." JAMA, 244, p. 2045
  18. van Ieperen L (1984) "Sudden death during disulfiram-ethanol reaction." S Afr Med J, 66, p. 165
  19. Buening MK, et al. (1981) "Disulfiram-like reaction to beta-lactams." JAMA, 245, p. 2047
  20. Foster TS, Raehl CL, Wilson HD (1980) "Disulfiram-like reaction associated with a parenteral cephalosporin." Am J Hosp Pharm, 37, p. 858-9
  21. (2002) "Product Information. Flagyl (metronidazole)." Searle
  22. Elenbaas RM (1977) "Drug therapy reviews: management of the disulfiram-alcohol reaction." Am J Hosp Pharm, 34, p. 827-31
  23. (2001) "Product Information. Antabuse (disulfiram)." Wyeth-Ayerst Laboratories
  24. (2022) "Product Information. MetroGel-Vaginal (metroNIDAZOLE topical)." Curatek Pharmaceuticals Ltd
  25. Cina SJ, Russell RA, Conradi SE (1996) "Sudden death due to metronidazole/ethanol interaction." Am J Forensic Med Pathol, 17, p. 343-6
  26. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  27. Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
  28. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
  29. Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
  30. McMahon FG, Ryan JR, Jain AK, LaCorte W, Ginzler F (1987) "Absence of disulfiram-type reactions to single and multiple doses of cefonicid: a placebo-controlled study." J Antimicrob Chemother, 20, p. 913-8
  31. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
View all 31 references

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Drug and food interactions

Moderate

metroNIDAZOLE topical food

Applies to: metronidazole topical

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.

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