Metronidazole

Brand Names: Flagyl

Clinical Names: Metronidazole

Summary

generic name: Metronidazole

trade names: Flagyl®, MetroCream®, MetroGel®, MetroLotion™, Noritate™

type of drug: Antibiotic, antiprotozoal, amebicidal, trichomonacidal and bactericidal

used to treat: Parasitic infections, certain sexually transmitted diseases, stomach ulcers, gastrointestinal infections, and some cases of vaginitis; involving the following:
anaerobic gram-negative bacilli, including most Bacteroides species, Fusobacterium and Veillonella; anaerobic gram-positive cocci including Clostridium, Eubacterium, Peptococcus and Peptostreptococcus; Metronidazole is also active against G. vaginalis and the protozoa E. histolytica, Trichomonas vaginalis and Giardia lamblia; Metronidazole acts primarily against the trophozoite forms of E. histolytica and has limited activity against the encysted forms.

overview of interactions:
• substance affected by drug: Alcohol

• diet affecting drug performance: Food

• nutrient affecting drug toxicity: Antioxidants

• herb affecting drug toxicity: Silybum marianum (Milk Thistle)



Interactions

substance affected by drug: Alcohol

• research: Metronidazole can produce a reaction similar to that of disulfiram (Antabuse) when administered to patients drinking ethanol. This drug/chemical interaction results in accumulation of acetaldehyde in the blood. Acetaldehyde is hepatotoxic, cardiotoxic, and arrythmogenic. Typical symptoms include light-headedness, headache, facial flushing, nausea, stomach pains, and shortness of breath. Cases have been reported of fatal outcomes resulting from this interaction.
(Cina SJ, et al. Am J Forensic Med Pathol 1996 Dec;17(4):343-346; Tunguy-Desmarais GP. S Afr Med J. 1983 May 28;63(22):836; Plosker GL. Clin Pharm. 1987 Mar;6(3):189, 192-193; Harries DP, et al. Scott Med J. 1990 Dec;35(6):179-180.)

• dietary concerns: Individuals taking metronidazole should refrain from drinking alcohol and avoid consuming alcohol-containing products while taking the drug and for three days afterwards. It is also advisable to read all product labels carefully for alcohol content.

• nutrient affecting drug toxicity: Antioxidants

• mechanism: Metronidazole can cause serious side effects, especially involving the digestion, liver and central nervous system. The mutagenicity of metronidazole has been extensively reported.

• research: Hrelia et al conducted research on antioxidants and the metronidazole-induced mutagenicity in the livers, kidneys and lungs of mice. After treating the mice with butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT), by intraperitoneal injection and oral intubation, they found significantly reduced liver- and kidney-mediated mutagenicity of metronidazole. While they concluded that BHA and BHT themselves might produce possible adverse effects, they still suggested the potential value of prophylactic use of antioxidants in reducing the risk of cancer due to metronidazole.
(Hrelia P, et al. Drugs Exp Clin Res 1987;13(9):577-583.)

• nutritional support: While the data available is speculative, antioxidants could potentially play a role in protecting against the adverse effects of metronidazole. Individuals taking metronidazole, even for 7-10 days, should consult their prescribing physician, pharmacist, and/or a nutritionally trained healthcare professional about the possible benefits of supplementing with antioxidant nutrients.

diet affecting drug performance: Food

• research: The simultaneous ingestion of food and metronidazole can result in delayed absorption of the drug. 

• nutritional concerns: Physicians and pharmacists often advise patients to take the drug with food or milk if it causes an upset stomach.
(Holt GA. 1998, 173.)

herb affecting drug toxicity: Silybum marianum (Milk Thistle)

• mechanism: Metronidazole can cause serious side effects, especially involving the digestion, liver and central nervous system.

• herbal support: Silybum is well-known for its proven effectiveness in protecting the liver from toxic insults by drugs and other chemicals. While Silybum has not been specifically researched with regard to its hepatoprotective effect against metronidazole, its known properties and actions are well-suited to the task of reducing the drug's potentially damaging effects on the liver.


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Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

Cina SJ, Russell RA, Conradi SE. Sudden death due to metronidazole/ethanol interaction. Am J Forensic Med Pathol 1996 Dec;17(4):343-346.

De Martiis M, Fontana M, Assogna G, D'Ottavi R, D'Ottavi O. [Milk thistle (Silybum marianum) derivatives in the therapy of chronic hepatopathies]. Clin Ter 1980 Aug 15;94(3):283-315. [Article in Italian]

Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998 Feb;93(2):139-143.
Abstract: Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. As interest in alternative therapy has emerged in the United States, gastroenterologists have encountered increasing numbers of patients taking silymarin with little understanding of its purported properties. Silymarin and its active constituent, silybin, have been reported to work as antioxidants scavenging free radicals and inhibiting lipid peroxidation. Studies also suggest that they protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. In this article we review silymarin's history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.

Harries DP, Teale KF, Sunderland G. Metronidazole and alcohol: potential problems. Scott Med J. 1990 Dec;35(6):179-180.

Hrelia P, Murelli L, Paolini M, Cantelli-Forti G. In vivo protective role of antioxidants against genotoxicity of metronidazole and azanidazole. Drugs Exp Clin Res 1987;13(9):577-583.
Abstract: The mutagenicity of metronidazole and azanidazole has been extensively reported. Previous experiments demonstrated, by means of the intrasanguineous host-mediated assay, that they significantly induced mutagenicity in liver, kidney and lung of mice. The treatment of mice with butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) by two different routes of administration (i.p. injection and oral intubation) significantly reduced liver- and kidney-mediated mutagenicity of azanidazole and metronidazole. No significant differences were observed between the routes of treatment in terms of protective effect on genotoxicity of azanidazole in the considered organs, whereas i.p. administration was the most suppressive on the mutagenicity of metronidazole. Even if BHT was the most effective agent in preventing mutation induction in mice, a detectable toxicity, in terms of increased mutagenicity, was evaluated in the liver. Evidence of lung abnormalities was also seen. The results suggest that the possible adverse effects on biological systems limit the prophylactic use of BHA and BHT in preventing the action of chemical carcinogens in man.

Morazzoni P, Bombardelli E. Silybum marianum (Carduus marianus). Fitoterapia 1995;66:3-42 (Review).

Muzes G, Deak G, Lang I, Nekam K, Niederland V, Feher J. [Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease]. Orv Hetil 1990 Apr 22;131(16):863-866. [Article in Hungarian]
Abstract: A double blind study. Antioxidant and antiperoxidative effects of the free radical scavenger agent silymarin (Legalon) were investigated in patients with chronic alcoholic liver disease in a double blind clinical trial. Six month treatment (at a daily dose of 420 mg) with silymarin significantly enhanced the originally low superoxide dismutase activity of erythrocytes and lymphocytes and also restored the diminished superoxide dismutase expression on lymphocytes as measured by flow-cytofluorimetry. In addition, silymarin therapy markedly increased the serum level of ree--SH groups and the activity of glutathione peroxidase. In contrast, a considerable fall in serum malondialdehyde concentration was detected in patients having received silymarin. However, in case of placebo-treated patients the above mentioned parameters of antioxidant defense system and lipid peroxidation failed to change significantly. These data indirectly suggest that antioxidant, antiperoxidative effects might be important factors in the mechanism of hepatoprotective action of silymarin.

Plosker GL. Possible interaction between ethanol and vaginally administered metronidazole. Clin Pharm. 1987 Mar;6(3):189, 192-193.

Threlkeld DS, ed. Systemic Anti-Infectives, Metronidazole. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Nov 1992.

Tunguy-Desmarais GP. Interaction between alcohol and metronidazole. S Afr Med J. 1983 May 28;63(22):836.