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Drug Interactions between metronidazole topical and ritonavir

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

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Interactions between your drugs

Moderate

metroNIDAZOLE topical ritonavir

Applies to: metronidazole topical and ritonavir

GENERALLY AVOID: Ritonavir capsules, ritonavir oral solution, lopinavir-ritonavir oral solution, and tipranavir capsules all contain alcohol, which 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 further information is available, use of ritonavir capsules, ritonavir oral solution, lopinavir-ritonavir oral solution, or tipranavir capsules 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. van Ieperen L (1984) "Sudden death during disulfiram-ethanol reaction." S Afr Med J, 66, p. 165
  18. Buening MK, et al. (1981) "Disulfiram-like reaction to beta-lactams." JAMA, 245, p. 2047
  19. Foster TS, Raehl CL, Wilson HD (1980) "Disulfiram-like reaction associated with a parenteral cephalosporin." Am J Hosp Pharm, 37, p. 858-9
  20. Elenbaas RM (1977) "Drug therapy reviews: management of the disulfiram-alcohol reaction." Am J Hosp Pharm, 34, p. 827-31
  21. (2022) "Product Information. MetroGel-Vaginal (metroNIDAZOLE topical)." Curatek Pharmaceuticals Ltd
  22. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  23. Cina SJ, Russell RA, Conradi SE (1996) "Sudden death due to metronidazole/ethanol interaction." Am J Forensic Med Pathol, 17, p. 343-6
  24. (2001) "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation
  25. Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
  26. (2001) "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical
  27. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
  28. Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
  29. 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
  30. (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
  31. (2005) "Product Information. Aptivus (tipranavir)." Boehringer-Ingelheim
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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Moderate

ritonavir food

Applies to: ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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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

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