What are the main indications for metronidazole. How does metronidazole work against anaerobic bacteria. What are the proper dosing guidelines for metronidazole. How is metronidazole administered in various forms. What are the potential side effects of metronidazole. How does metronidazole interact with other medications. Why is antibiotic stewardship important when prescribing metronidazole.

Understanding Metronidazole: A Versatile Antibiotic

Metronidazole stands as a cornerstone in the treatment of various infections, particularly those caused by anaerobic bacteria and certain protozoans. This powerful antibiotic has earned its place in the medical arsenal due to its broad spectrum of activity and effectiveness against a wide range of pathogens.

Healthcare professionals rely on metronidazole for treating conditions ranging from gastrointestinal infections to skin and soft tissue infections. Its versatility makes it a valuable tool in combating diverse microbial threats.

Key Indications for Metronidazole Use

Metronidazole is FDA-approved for numerous infections, including:

• Trichomoniasis
• Amebiasis (intestinal and liver)
• Giardiasis
• Bacterial vaginosis
• Anaerobic bacterial infections (e.g., those caused by Bacteroides, Clostridium, and Fusobacterium species)
• Helicobacter pylori eradication (as part of combination therapy)

Additionally, metronidazole finds off-label use in managing conditions such as:

• Crohn’s disease
• Periodontitis
• Bite wound infections
• Clostridioides difficile infections
• Pouchitis following ileal pouch-anal anastomosis

The Mechanism of Action: How Metronidazole Defeats Pathogens

Metronidazole’s efficacy stems from its unique mechanism of action, which specifically targets anaerobic organisms. How does this antibiotic work to eliminate harmful microbes?

The process occurs in four main steps:

1. Entry into the organism: Metronidazole diffuses across cell membranes of both anaerobic and aerobic pathogens.
2. Reductive activation: Intracellular transport proteins alter the chemical structure of metronidazole, creating a concentration gradient that drives further uptake and promotes the formation of cytotoxic free radicals.
3. Interaction with intracellular targets: The activated drug and its toxic byproducts interact with the pathogen’s DNA, causing strand breakage and destabilization of the DNA helix.
4. Breakdown of cytotoxic products: The final step involves the degradation of the toxic compounds, ultimately leading to cell death.

This mechanism explains why metronidazole is particularly effective against anaerobic bacteria and certain protozoans, while having limited activity against aerobic organisms.

Dosing Guidelines: Ensuring Optimal Efficacy

Proper dosing of metronidazole is crucial for achieving therapeutic success while minimizing the risk of side effects. How should healthcare providers determine the appropriate dosage for different conditions?

The dosing of metronidazole varies depending on the specific infection being treated, the patient’s age, weight, and overall health status. Here are some general guidelines for common indications:

• Bacterial vaginosis: 500 mg orally twice daily for 7 days
• Trichomoniasis: 2 g orally as a single dose, or 500 mg twice daily for 7 days
• Amebiasis: 500-750 mg orally three times daily for 5-10 days
• Anaerobic infections: 7.5 mg/kg IV every 6 hours, or 500 mg orally every 8 hours
• H. pylori eradication: 500 mg orally twice daily for 10-14 days (as part of combination therapy)

It’s important to note that these are general guidelines, and dosing may need to be adjusted based on individual patient factors and the specific formulation of metronidazole being used.

Administration Routes: Tailoring Treatment to Patient Needs

Metronidazole’s versatility extends to its various routes of administration, allowing healthcare providers to tailor treatment to individual patient needs and specific infection sites. What are the different ways metronidazole can be administered?

Metronidazole is available in several formulations:

• Oral tablets and capsules: The most common form for treating systemic infections
• Intravenous solution: Used for severe infections or when oral administration is not possible
• Topical gel or cream: Applied to the skin for treating rosacea
• Vaginal gel: Used for localized treatment of bacterial vaginosis
• Extended-release tablets: Provide prolonged drug release for certain indications

The choice of formulation depends on the infection site, severity of the condition, and patient factors such as ability to tolerate oral medications.

Side Effects and Precautions: Balancing Benefits and Risks

While metronidazole is generally well-tolerated, it can cause side effects in some patients. What are the most common adverse reactions associated with metronidazole use?

Common side effects include:

• Nausea and vomiting
• Metallic taste in the mouth
• Headache
• Dizziness
• Dry mouth
• Abdominal discomfort

More serious, but less common, side effects can include:

• Peripheral neuropathy
• Seizures
• Encephalopathy
• Pseudomembranous colitis

Healthcare providers should be aware of these potential adverse effects and monitor patients closely, especially those on long-term or high-dose therapy.

Special Precautions

Certain patient populations require special consideration when prescribing metronidazole:

• Pregnancy: Metronidazole crosses the placenta and should be used with caution during pregnancy, especially in the first trimester.
• Breastfeeding: The drug is excreted in breast milk and may affect the infant. Temporary discontinuation of breastfeeding may be necessary.
• Liver impairment: Dosage adjustment may be required in patients with severe hepatic dysfunction.
• Alcohol interaction: Patients should avoid alcohol during treatment and for at least 48 hours after the last dose due to a potential disulfiram-like reaction.

Drug Interactions: Navigating Complex Treatment Regimens

Metronidazole can interact with various medications, potentially altering their effectiveness or increasing the risk of side effects. Which drug interactions should healthcare providers be particularly aware of?

Some notable interactions include:

• Warfarin: Metronidazole can enhance the anticoagulant effect, requiring close monitoring of INR.
• Lithium: Metronidazole may increase lithium levels, necessitating dose adjustments.
• Busulfan: Concomitant use can increase busulfan levels, potentially leading to severe toxicity.
• Disulfiram: Concurrent use can lead to psychotic reactions and should be avoided.
• Alcohol-containing products: Can cause a disulfiram-like reaction, including flushing, tachycardia, and nausea.

Healthcare providers should conduct a thorough medication review before initiating metronidazole therapy and monitor patients for potential interactions throughout treatment.

Antibiotic Stewardship: Preserving Metronidazole’s Efficacy

The rise of antibiotic resistance poses a significant threat to global health, making antibiotic stewardship crucial in preserving the effectiveness of drugs like metronidazole. How can healthcare providers contribute to responsible antibiotic use?

Key principles of antibiotic stewardship for metronidazole include:

• Accurate diagnosis: Ensure that metronidazole is only prescribed for confirmed or strongly suspected anaerobic or protozoal infections.
• Appropriate dosing: Use the correct dose and duration of therapy to maximize efficacy while minimizing the risk of resistance development.
• Narrow-spectrum alternatives: Consider narrower-spectrum antibiotics when possible, reserving metronidazole for cases where it is specifically indicated.
• Combination therapy: Use metronidazole in combination with other antibiotics when appropriate, such as in H. pylori eradication regimens.
• Monitoring and de-escalation: Regularly assess the need for continued therapy and switch to narrower-spectrum agents or discontinue treatment when appropriate.

By adhering to these principles, healthcare providers can help preserve metronidazole’s effectiveness for future patients while ensuring optimal outcomes for current ones.

Future Perspectives: Metronidazole in the Era of Antimicrobial Resistance

As antimicrobial resistance continues to evolve, what does the future hold for metronidazole? Researchers are exploring several avenues to enhance its utility and combat resistance:

• Novel formulations: Development of extended-release and nanoparticle-based formulations to improve pharmacokinetics and reduce side effects.
• Combination therapies: Investigation of synergistic combinations with other antimicrobials to enhance efficacy and prevent resistance.
• Repurposing: Exploration of metronidazole’s potential in treating emerging infectious diseases and non-infectious conditions.
• Resistance mechanisms: Ongoing research into understanding and overcoming resistance mechanisms in anaerobic bacteria.
• Precision medicine approaches: Development of rapid diagnostic tools to guide more targeted use of metronidazole.

These advancements may help ensure that metronidazole remains a valuable tool in the antimicrobial armamentarium for years to come.

Conclusion

Metronidazole continues to play a crucial role in treating a wide range of anaerobic and protozoal infections. Its unique mechanism of action, diverse formulations, and broad spectrum of activity make it an indispensable antibiotic in modern healthcare. However, responsible use through antibiotic stewardship is essential to preserve its efficacy in the face of growing antimicrobial resistance.

Healthcare providers must balance the benefits of metronidazole therapy with potential risks, considering factors such as appropriate indications, dosing, administration routes, and potential drug interactions. By doing so, they can optimize patient outcomes while contributing to the global effort to combat antibiotic resistance.

As research continues to uncover new applications and improve our understanding of metronidazole, this versatile antibiotic is likely to remain a cornerstone of infectious disease treatment for the foreseeable future. Ongoing vigilance, responsible prescribing practices, and continued scientific inquiry will be key to maximizing its potential and ensuring its long-term effectiveness in clinical practice.

Metronidazole – StatPearls – NCBI Bookshelf

Continuing Education Activity

Metronidazole is one of the mainstay drugs for the treatment of anaerobic bacterial infections, protozoal infections, and microaerophilic bacterial infections. It is cytotoxic to facultative anaerobic microorganisms. It is used to treat intestinal amebiases, liver amebiasis, bacterial septicemia, bone and joint infections, meningitis, brain abscess, endocarditis, endometritis, bacterial vaginosis, intra-abdominal infections, lower respiratory tract infections, skin structure infections, and surgical prophylaxis colorectal surgeries. This activity will highlight the mechanism of action, adverse event profile, contraindications, monitoring, and other key factors pertinent to interprofessional team members in the care of patients being treated with this medication.

Objectives:

• Describe the indications to begin metronidazole therapy.

• Outline dosing of metronidazole for some of the more common indications.

• Describe the importance of antibiotic stewardship when initiating a broad-spectrum antimicrobial like metronidazole.

• Explain the importance of antibiotic stewardship and how it affects antimicrobial selection as it pertains to improving care coordination among the interprofessional team when initiating antibiotic therapy with metronidazole.

Access free multiple choice questions on this topic.

Indications

Metronidazole is one of the mainstay drugs for the treatment of anaerobic bacterial infections, protozoal infections, and microaerophilic bacterial infections. It is cytotoxic to facultative anaerobic microorganisms.

Metronidazole is FDA-approved for treating protozoal infections such as Trichomoniasis vaginalis, Entamoeba histolytica, Giardia lamblia, blastocysts, and Balantidium coli. It is also FDA approved to treat anaerobic bacterial infections caused by Bacteroides species, Fusobacterium species, Clostridium species, Gardnerella vaginalis, Helicobacter pylori, Prevotella species, Porphyromonas species, and Biophilia Wadsworth. [1] Therefore, it is not surprising that metronidazole is widely accepted and FDA-approved for the treatment of a broad range of infections: intestinal amebiases, liver amebiasis, bacterial septicemia, bone and joint infections, central nervous system (CNS) infections (meningitis and brain abscess), endocarditis, gynecologic infections (endometritis, tubo-ovarian abscess, bacterial vaginosis), intra-abdominal infections, lower respiratory tract infections, skin structure infections, and surgical prophylaxis (colorectal surgeries).[2]

Topical metronidazole is indicated for rosacea. It is used intravaginally for bacterial vaginosis

Metronidazole has additional off-label uses in the management of other conditions and infections, including balantidiases, bite wound infections, animal and human bites, Clostridioides (formerly Clostridium difficile), Crohn disease, post-surgical resection management, perianal fistulas, Dietamoeba fragilis infections, giardiasis, Helicobacter pylori eradication, periodontitis, post ileal pouch-anal anastomosis (pouchitis), and tetanus. [2]

Metronidazole has rapid bactericidal effects against anaerobic bacteria with a killing rate proportional to the drug concentration. Concentration-dependent bactericidal properties have been demonstrated against Entamoeba histolytica and Trichomonas vaginalis.[3][4] Furthermore, it kills Bacteroides fragilis, and Clostridium perfringens more rapidly than treatment doses of clindamycin. It also penetrates the blood-brain barrier.[5]

Mechanism of Action

Metronidazole diffuses into the organism, inhibits protein synthesis by interacting with DNA, and causes a loss of helical DNA structure and strand breakage. Therefore, it causes cell death in susceptible organisms.

The mechanism of action of metronidazole occurs through a four-step process. Step one is the entry into the organism by diffusion across the cell membranes of anaerobic and aerobic pathogens. However, antimicrobial effects are limited to anaerobes.[6] Step two involves reductive activation by intracellular transport proteins by altering the chemical structure of pyruvate-ferredoxin oxidoreductase. The reduction of metronidazole creates a concentration gradient in the cell that drives uptake of more drugs and promotes free radical formation that is cytotoxic.[7] Step three, interactions with intracellular targets, is achieved by cytotoxic particles interacting with host cell DNA resulting in DNA strand breakage and fatal destabilization of the DNA helix.[8] Step four is the breakdown of cytotoxic products. Metronidazole is also cytotoxic to facultatively anaerobic bacteria like Helicobacter pylori and Gardnerella vaginalis, but the mechanism of action to these pathogens is not well understood.[6]

Administration

Metronidazole may be administered orally, intravenously, or topically. It comes in capsule, tablet, topical and intravenous forms.[9]

• The standard capsule dosing is 375 mg. Standard tablet dosing is 250 mg or 500 mg. Oral administration can be taken with food to help minimize stomach discomfort. The extended-release tablets should be administered on an empty stomach 1 hour before or 2 hours after meals. It should not be split or crushed.

• Standard intravenous preparation and dosing is 5 mg/mL (100mL) and 500 mg (100 mL), respectively. When administered intravenously, the drug solution should not come in contact with equipment containing aluminum. Infusion of the intravenous solution should be over 30 to 60 minutes. 

• The topical application gel is 0.75% and 37.5 mg per applicator and is applied vaginally.

Dosing of metronidazole for some of the more common indications is listed below:[10]

• Dosing for amebiasis, both intestinal (acute dysentery) and extraintestinal:[11]

• Dosing for bacterial vaginosis:[12] 

• Dosing for pelvic inflammatory disease (PID) treatment:

  • Mild/moderate PID: Oral: 500 mg twice a day for 14 days (may be added to combination therapy)

  • PID with tubo-ovarian abscess, initial treatment (as an alternative regimen): IV: 500 mg every 8 hours as part of an appropriate combination regimen

  • PID with tubo-ovarian abscess, oral therapy subsequent to clinical improvement on a parenteral regimen: Oral: 500 mg twice daily with doxycycline for at least 14 days

• Dosing for trichomoniasis infection:

  • Initial treatment: Oral: 2 g in a single dose or 500 mg twice daily for seven days (preferred regimen in HIV-infected women)

  • Persistent or recurrent infection (treatment failure single-dose therapy): Oral: 500 mg twice daily for 7 days for the failure of 2 g single-dose regimen

• Dosing for Giardiasis:[13] 

• Dosing for intra-abdominal infections:[14] 

  • Oral, IV: 500 mg every 8 hours as in an appropriate combination regimen. Therapy duration is 4 to 7 days following adequate source control, and a longer duration is necessary for uncomplicated appendicitis and diverticulitis managed nonoperatively.

• Dosing for skin and soft tissue infections:[15]

  • Necrotizing infections (a component of an appropriate combination regimen): IV: 500 mg every 6 hours – continue until debridement is no longer required, the patient has clinically improved, and is afebrile for 48 to 72 hours

• Dosing for surgical site infections, incisional (intestinal or GU tract; axilla or perineum), warranting anaerobic coverage:

• Dosing for surgical prophylaxis:[16]

  • IV: 500 mg within one hour before surgical incision in a regimen with other antibiotics; recommended for select procedures involving the head and neck, GI tract, or urologic tract

• Dosing for oral, colorectal surgical prophylaxis:

  • Oral: 1 g every 3 to 4 hours for three doses with additional oral antibiotics, following mechanical bowel preparation the evening prior to a morning surgery with subsequent appropriate IV antibiotic prophylaxis regimen

• Dosing for Helicobacter pylori eradication:[17]

  •  The triple regimen with clarithromycin: Oral: Metronidazole 500 mg 3 times each day combined with clarithromycin 500 mg twice a day and a standard-dose or double-dose proton pump inhibitor (PPI) twice daily; continue regimen for 14 days

  • Quadruple regimen with bismuth: Oral: Metronidazole 250 mg 4 times each day or 500 mg 3 or 4 times each day in combination with bismuth subsalicylate 300 to 524 mg or bismuth subsalicylate 120 to 300 mg 4 times each day, tetracycline 500 mg 4 times each day, and a standard-dose PPI twice each day; continue regimen for 10 to 14 days

  • Concomitant regimen: Oral: Metronidazole 500 mg twice each day in combination with clarithromycin 500 mg twice each day, amoxicillin 1 g twice each day, and a standard-dose PPI twice each day; continue regimen for 10 to 14 days

• Dosing for Clostridium difficile infection (CDI):[18]

  • Metronidazole is no longer a first-line antibiotic choice. “Either vancomycin or fidaxomicin are preferred agents over metronidazole for initial episodes of CDI – if access to vancomycin or fidaxomicin is limited, metronidazole is an option for an initial episode of nonsevere CDI only at a dose of 500 mg orally three times daily for ten days

  • Fulminant Clostridium difficile infection: Vancomycin administered orally is the regimen of choice; in the presence of ileus, vancomycin can also be administered rectally – IV metronidazole should be administered 500 mg every 8 hours together with oral or rectal vancomycin, particularly if an ileus is present.

• Dosing for rosacea with 1% gel or cream daily, or 0.75% cream or lotion twice a day.

Adverse Effects

The primary adverse effects of metronidazole include confusion, peripheral neuropathy, metallic taste, nausea, vomiting, and diarrhea. Adverse events seen in greater than 10% of the population include headache (18%), vaginitis (15%), and nausea (10% to 12%). Adverse events affecting less than 10% of the population are metallic taste (9%), dizziness (4%), genital pruritus (5%), abdominal pain (4%), diarrhea (4%), xerostomia (2%), dysmenorrhea (3%), urine abnormality (3%), urinary tract infection (2%), bacterial infection (7%), candidiasis (3%), flu-like symptoms (6%), upper respiratory tract infection (4%), pharyngitis (3%), and sinusitis (3%). Rarely, there are reports of transient leukopenia and neutropenia as well.[19][20]

Metronidazole comes with a black box warning that it may be carcinogenic based on some animal studies in mice and rats. However, the risks are considered low, and additional follow-up studies of patients treated do not reveal an increased cancer incidence. As with any medication choice, physicians and patients must decide whether the benefit from therapy outweighs the potential risk. The use of metronidazole should be reserved for conditions approved by the FDA; it should not be used prophylactically or unnecessarily. [21]

Additional warnings and precautions for metronidazole exist. Prolonged drug courses can cause severe neurological disturbances due to the risk of cumulative neurotoxicity. Monitor for neurologic sequela and discontinue therapy if any abnormal neurologic symptoms occur.[21] Prolonged use may also result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis. There are reports of CDAD even after more than two months of postantibiotic treatment. Candidiasis infection may also be more prominent during metronidazole treatment.[22]

Contraindications

Metronidazole is contraindicated in patients with documented hypersensitivity to the drug or its components, and it should be avoided in first-trimester pregnancy. Patients should also avoid consuming alcohol or products containing propylene glycol while taking metronidazole and within three days of therapy completion. Metronidazole is likewise contraindicated if there has been recent disulfiram use within the past two weeks. [9]

Monitoring

During and after prolonged therapy or repeated courses, complete blood count (CBC) with differential requires monitoring. Carefully observe patients for the onset of neurologic symptoms and consider discontinuing metronidazole when or if new neurologic symptoms occur. Elderly patients and previously diagnosed patients with severe hepatic impairment and/or end-stage renal disease should also be monitored closely.[9]

Toxicity

There have been reports of disulfiram-like reactions in patients drinking alcohol while administered systemic or vaginal metronidazole. A typical disulfiram reaction causes flushing, tachycardia, palpitations, nausea, and vomiting. Alcohol should be avoided during treatment and from up to forty-eight hours to fourteen days after treatment completion, depending on the source; the manufacturer’s product information recommends avoiding alcohol ingestion during metronidazole therapy and for at least 48 hours afterward. Ethanol-containing medications such as elixirs and tipranavir, capsules, intravenous (IV) anidulafungin, IV trimethoprim-sulfamethoxazole, and many cough/cold syrups can also lead to a disulfiram-like reaction when ingested with metronidazole. [9][23]

Enhancing Healthcare Team Outcomes

There should be judicious prescribing of metronidazole by providers only for known indications and high clinical suspicion for needing treatment of anaerobic bacterial infections, protozoal infections, and microaerophilic bacterial infections. Overprescribing may contribute to increasing future antibiotic resistance to the drug, so a pharmacy consult is necessary for the prescriber to ensure directed therapy. The documentation already exists regarding increased resistance to metronidazole in the treatment of C. difficile infections. Also, prescribers, nurses, and pharmacists should routinely educate patients to abstain from alcoholic beverages while taking metronidazole, which will help lead to fewer disulfiram reaction symptoms; nursing will play a role in this monitoring and for other potential adverse effects. The patient should also be informed by the health care provider of the possible change in urine color while on this medicine. The team of health professionals, including physicians, physician assistants, nurses, and pharmacists, must work together to provide the best care for these patients when using metronidazole in any formulation. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Pankuch GA, Jacobs MR, Appelbaum PC. Susceptibilities of 428 gram-positive and -negative anaerobic bacteria to Bay y3118 compared with their susceptibilities to ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and cefoxitin. Antimicrob Agents Chemother. 1993 Aug;37(8):1649-54. [PMC free article: PMC188035] [PubMed: 8215278]

2.

Löfmark S, Edlund C, Nord CE. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis. 2010 Jan 01;50 Suppl 1:S16-23. [PubMed: 20067388]

3.

Ravdin JI, Skilogiannis J. In vitro susceptibilities of Entamoeba histolytica to azithromycin, CP-63,956, erythromycin, and metronidazole. Antimicrob Agents Chemother. 1989 Jun;33(6):960-2. [PMC free article: PMC284263] [PubMed: 2548442]

4.

Nix DE, Tyrrell R, Müller M. Pharmacodynamics of metronidazole determined by a time-kill assay for Trichomonas vaginalis. Antimicrob Agents Chemother. 1995 Aug;39(8):1848-52. [PMC free article: PMC162837] [PubMed: 7486930]

5.

Ralph ED, Kirby WM. Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens. Antimicrob Agents Chemother. 1975 Oct;8(4):409-14. [PMC free article: PMC429358] [PubMed: 172007]

6.

Edwards DI. Nitroimidazole drugs–action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother. 1993 Jan;31(1):9-20. [PubMed: 8444678]

7.

Edwards DI. Reduction of nitroimidazoles in vitro and DNA damage. Biochem Pharmacol. 1986 Jan 01;35(1):53-8. [PubMed: 3940526]

8.

Tocher JH, Edwards DI. The interaction of reduced metronidazole with DNA bases and nucleosides. Int J Radiat Oncol Biol Phys. 1992;22(4):661-3. [PubMed: 1544834]

9.

Finegold SM. Metronidazole. Ann Intern Med. 1980 Oct;93(4):585-7. [PubMed: 7436193]

10.

Sexually Transmitted Diseases: Summary of 2015 CDC Treatment Guidelines. J Miss State Med Assoc. 2015 Dec;56(12):372-5. [PubMed: 26975162]

11.

Gonzales MLM, Dans LF, Sio-Aguilar J. Antiamoebic drugs for treating amoebic colitis. Cochrane Database Syst Rev. 2019 Jan 09;1(1):CD006085. [PMC free article: PMC6326239] [PubMed: 30624763]

12.

van Schalkwyk J, Yudin MH., INFECTIOUS DISEASE COMMITTEE. Vulvovaginitis: screening for and management of trichomoniasis, vulvovaginal candidiasis, and bacterial vaginosis. J Obstet Gynaecol Can. 2015 Mar;37(3):266-274. [PubMed: 26001874]

13.

Gardner TB, Hill DR. Treatment of giardiasis. Clin Microbiol Rev. 2001 Jan;14(1):114-28. [PMC free article: PMC88965] [PubMed: 11148005]

14.

Mazuski JE, Tessier JM, May AK, Sawyer RG, Nadler EP, Rosengart MR, Chang PK, O’Neill PJ, Mollen KP, Huston JM, Diaz JJ, Prince JM. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect (Larchmt). 2017 Jan;18(1):1-76. [PubMed: 28085573]

15.

Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014 Jul 15;59(2):147-59. [PubMed: 24947530]

16.

Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA., American Society of Health-System Pharmacists. Infectious Disease Society of America. Surgical Infection Society. Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013 Feb 01;70(3):195-283. [PubMed: 23327981]

17.

Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-239. [PubMed: 28071659]

18.

McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994. [PMC free article: PMC6018983] [PubMed: 29562266]

19.

McKendrick MW, Geddes AM. Neutropenia associated with metronidazole. Br Med J. 1979 Sep 29;2(6193):795. [PMC free article: PMC1596438] [PubMed: 519201]

20.

Smith JA. Neutropenia associated with metronidazole therapy. Can Med Assoc J. 1980 Aug 09;123(3):202. [PMC free article: PMC1704722] [PubMed: 7260762]

21.

Hernández Ceruelos A, Romero-Quezada LC, Ruvalcaba Ledezma JC, López Contreras L. Therapeutic uses of metronidazole and its side effects: an update. Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):397-401. [PubMed: 30657582]

22.

Saginur R, Hawley CR, Bartlett JG. Colitis associated with metronidazole therapy. J Infect Dis. 1980 Jun;141(6):772-4. [PubMed: 7391617]

23.

Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000 Feb;34(2):255-7. [PubMed: 10676835]

Disclosure: Connor Weir declares no relevant financial relationships with ineligible companies.

Disclosure: Jacqueline Le declares no relevant financial relationships with ineligible companies.

Metronidazole: MedlinePlus Drug Information

pronounced as (me troe ni’ da zole)

To use the sharing features on this page, please enable JavaScript.

Metronidazole can cause cancer in laboratory animals. Talk to your doctor about the risks and benefits of taking this medication.

Metronidazole capsules and tablets are used to treat infections of the reproductive system, gastrointestinal (GI) tract, skin, heart, bone, joint, lung, blood, nervous system, and other areas of the body. Metronidazole capsules and tablets are also used to treat sexually transmitted diseases (STDs). Metronidazole extended-release (long-acting) tablets are used to treat bacterial vaginosis (an infection caused by too much of certain types of harmful bacteria in the vagina) in women. Metronidazole is in a class of medications called nitroimidazole antimicrobials. It works by stopping the growth of bacteria.

Antibiotics will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Metronidazole comes as a tablet, an extended-release tablet, and as a capsule to take by mouth. Metronidazole capsules and tablets are usually taken as a one-time dose (or divided into two doses on 1 day) or two to four times daily for up to 10 days or longer. Metronidazole extended-release tablets are usually taken once daily at least 1 hour before or 2 hours after a meal for 7 days. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take metronidazole exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the extended-release tablets whole; do not split, chew, or crush them.

Continue to take this medication even if you feel well. Do not stop taking it without talking to your doctor. If you stop taking this medication too soon or skip doses, your infection may not be completely treated and the bacteria may become resistant to antibiotics.

Metronidazole tablets are used to treat bacterial vaginosis in women.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking metronidazole,

• tell your doctor and pharmacist if you are allergic to metronidazole, secnidazole (Solosec), tinidazole (Tindamax), any other medications, or any of the ingredients in metronidazole preparations. Ask your pharmacist for a list of the ingredients.
• tell your doctor if you are taking or have taken disulfiram (Antabuse). Your doctor may tell you not to take metronidazole if you are taking disulfiram or have taken it within the past 2 weeks.
• tell your doctor and pharmacist what prescription, nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin, Jantoven), busulfan (Busulfex, Myleran), cimetidine (Tagamet HB), lithium (Lithobid), phenobarbital, and phenytoin (Dilantin, Phenytek).
• tell your doctor if you have or have ever had Crohn’s disease, or blood, kidney, or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking metronidazole, call your doctor. Women who are pregnant generally should not take metronidazole during the first trimester (first 3 months) of pregnancy.
• do not drink alcoholic beverages or take products with alcohol or propylene glycol while taking this medication and for at least 3 days after your final dose. Alcohol and propylene glycol may cause nausea, vomiting, stomach cramps, headache, sweating, and flushing (redness of the face) when taken with metronidazole.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Metronidazole may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• vomiting
• nausea
• diarrhea
• constipation
• upset stomach
• stomach cramps
• loss of appetite
• headache
• dry mouth
• sharp, unpleasant metallic taste
• furry tongue; mouth or tongue irritation

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

• numbness, pain, burning, or tingling in your hands or feet
• seizures
• rash
• itching
• hives
• peeling or blistering skin
• flushing
• stuffy nose, fever, sore throat, or other signs of infection
• joint pain
• dizziness
• difficulty speaking
• problems with coordination
• confusion
• agitation

Metronidazole may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

Symptoms of overdose may include the following:

• nausea
• vomiting
• loss of muscle coordination
• numbness, pain, burning, or tingling in your hands or feet
• seizures

• Flagyl^®
• Flagyl^® 375
• Flagyl^® ER

Last Revised – 12/15/2017

Browse Drugs and Medicines

Metronidazole

Instructions for use of the medicinal product Metronidazole tablets for the treatment of farm animals in diseases of protozoal etiology (Developer organization: NPK Askont+, Moscow region)

I.

GENERAL INFORMATION

1. Trade name of the medicinal product : Metronidazole tablets (Tabulettae Metronidazoli). International non-proprietary name: metronidazole.

2. Dosage form: tablets for oral administration. Metronidazole tablets weighing 0.25 g contain in 1 tablet metronidazole – 0.0625 g as an active substance (DI), and as excipients: calcium stearate – 0.003 g, starch – 0.042 g, lactose – up to 0.25 g. Metronidazole tablets weighing 0.5 g contain 1 tablet as the active substance metronidazole – 0.125 g, and as excipients: calcium stearate – 0.003 g, starch – 0.05 g, lactose – up to 0.5 g.

3. The drug is produced in the form of tablets from white to white with a yellowish or greenish tint, weighing 0.25 g and 0.5 g Tablets are packaged in 100, 250, 500 and 1000 pieces in polyethylene film bags and jars made of polypropylene, closed with lids with a sealing element made of high pressure polyethylene. Each jar is supplied with instructions for use.

4. Store Metronidazole tablets in the manufacturer’s closed packaging in a dry place, protected from direct sunlight, away from food and feed, at a temperature of minus 10 °C to 40 °C. The shelf life of the medicinal product, subject to storage conditions, is 2 years from the date of manufacture. It is forbidden to use the medicinal product after the expiration date.

5. Metronidazole tablets should be kept out of the reach of children.

6. The unused medicinal product is disposed of in accordance with the requirements of the legislation.

II. PHARMACOLOGICAL PROPERTIES

7. Metronidazole is active against a number of protozoa, including balantidia, trichomonads, giardia, amoebas and histomonads, as well as many anaerobes and clostridia. The mechanism of action of metronidazole is to block the nitro group of proteins and disrupt the redox balance in the cell of microorganisms, which leads to the accumulation of toxic products that interact with the DNA of microorganisms, resulting in their death. When administered orally, metronidazole is rapidly absorbed in the gastrointestinal tract, distributed in organs, tissues and biological fluids. It is excreted from the body unchanged and as metabolites with urine and partly with faeces, in lactating animals also with milk. According to the degree of impact on the body, metronidazole tablets are classified as moderately hazardous substances (hazard class 3 according to GOST 12.1.007), at recommended doses they are well tolerated by animals, do not have embryotoxic, teratogenic and hepatotoxic properties.

III. HOW TO USE

8. Metronidazole tablets are prescribed for therapeutic purposes in cattle trichomoniasis, balantidiasis and swine dysentery.

9. Metronidazole tablets should not be used in case of individual hypersensitivity of the animal to metronidazole, as well as in pregnant animals.

10. For the treatment of cows and bulls with trichomoniasis, the drug is prescribed individually orally for 3-4 days, twice a day at the rate of 10 mg of metronidazole (DV) per 1 kg of animal weight, which is: 1 tablet weighing 0, 25 g per 6. 25 kg of animal weight, 1 tablet weighing 0.5 g per 12.5 kg of animal weight. At the same time, the drug is applied topically in the form of a 1% (according to active ingredient) suspension in saline. To prepare a suspension, 16 tablets weighing 0.25 g or 8 tablets weighing 0.5 g are ground and mixed with 100 ml of saline. The resulting suspension immediately before use is thoroughly shaken and the vagina or prepuce is washed with it two to four times with an interval of 24 hours and a consumption rate of 25-50 ml of the suspension. For the treatment of pigs with balantidiasis, the drug is administered orally twice a day for 3 consecutive days, at the rate of 10 mg of metronidazole (DV) per 1 kg of animal weight, which is: 1 tablet weighing 0.25 g per 6.25 kg of animal weight; 1 tablet weighing 0.5 g per 12.5 kg of animal weight. For the treatment of pigs with dysentery, the drug is used orally once a day for 4 days in a row, at the rate of 25 mg of AI per 1 kg of animal weight, which is: 10 tablets weighing 0. 25 g per 25 kg of animal weight, 10 tablets weighing 0, 5 g per 50 kg of animal weight. If necessary, the course of treatment of pigs is repeated after 7-10 days.

11. No symptoms of drug overdose have been identified. Features of the drug’s action during its first use and cancellation were not revealed.

12. Features of the drug’s action during its first use and cancellation were not revealed.

13. When using the medicinal product in accordance with this instruction, side effects and complications, as a rule, are not observed. With increased individual sensitivity of the animal to metronidazole and the appearance of allergic reactions, the use of the drug is stopped and desensitizing therapy is carried out.

14. The combined use of Metranidazole tablets with sulfonamides enhances the antimicrobial effect.

15. Slaughter of animals for meat is allowed no earlier than 5 days after the last use of the drug. The meat of animals compulsorily slaughtered before the expiration of the specified period may be used as feed for animals or for processing into meat and bone meal. Milk should not be used for food purposes within 36 hours after the last use of the drug. Milk obtained earlier than the established date, after boiling for 30 minutes, can be used as animal feed.

IV. PERSONAL PREVENTION MEASURES

16. When working with the drug Metronidazole tablets, you should follow the general rules of personal hygiene and safety, provided for when working with veterinary medicinal products. When working with the drug, it is forbidden to drink, smoke, eat. At the end of work, hands should be washed with warm water and soap.

17. People with hypersensitivity to the components of the drug should avoid direct contact with the drug. In case of accidental contact of the medicinal product with the skin or mucous membranes of the eyes, they must be washed with plenty of water. In case of allergic reactions or in case of accidental ingestion of the drug into the human body, you should immediately contact a medical institution (you should have instructions for using the drug or a label with you).

18. It is forbidden to use an empty drug container for household purposes, it must be disposed of with household waste.

19. Organization-manufacturer: OOO NPK Askont+; 142279, Moscow region, Serpukhov district, Obolensk settlement, st. Builders, corp. 2. The instruction was developed by NPK Askont+ LLC; 142279, Moscow region, Serpukhov district, Obolensk settlement, st. Builders, corp. 2.
Registration certificate number: RK-VP-4-1864-12

Metronidazole 5% – Veterinary drugs

Description : White to yellow clear solution for injection.

Composition : 1 ml contains: metronidazole – 50 mg.

Pharmacological properties : Antiprotozoal drug with antibacterial activity. Metronidazole belongs to the group of nitroimidazoles, has an effect on anaerobic bacteria (spore-forming and non-spore-forming), treponema, amoebae, histomonads, balantidia and trichomonads. Metronidazole acts on pathogens by blocking the nitro groups of proteins and disrupting the redox balance of the microorganism. When administered intramuscularly, it is rapidly distributed into the blood and other tissues, accumulating in the gastrointestinal tract. It is excreted from the body mainly with urine. Metronidazole 5% is classified as a low-hazard substance in the recommended doses, is well tolerated by animals, does not have a local irritating and sensitizing effect.

Indications : Dysentery of pigs caused by Treponema (Serpulina) hyodysenteriae and anaerobic bacteria, balantidiasis of pigs caused by Balantidium suis.

Application of : Metronidazole solution 5% is administered intramuscularly twice with an interval of 48 hours at a dose of 1 ml per 10 kg of animal weight (5 mg/kg of metronidazole) for dysentery and 2 ml per 10 kg of animal weight (10 mg/kg of metronidazole 5 %) with balantidiasis. If the volume of the injected solution exceeds 10 ml, it should be administered to animals in different places. In severe cases (especially with anaerobic infections) administered daily 1 time per day for 3-5 days. If necessary, the course of treatment is repeated after 10-15 days. At the same time, symptomatic treatment is carried out, vitamins are prescribed; carry out disinfection and deratization.

Side effects : Local reactions – sometimes itching, erythema, swelling at the injection site, which disappear spontaneously without treatment.

Contraindications : First third of pregnancy, simultaneous administration with ethanol-containing drugs.

Special instructions : In the event of an allergic reaction, the drug is discontinued and desensitizing therapy is carried out.

Warning : Slaughter of pigs for meat is allowed no earlier than 10 days after the last administration of the drug. The meat of animals compulsorily killed before the expiration of the specified period is used for feeding carnivorous animals or for the production of meat and bone meal. All work with the drug should be carried out in compliance with the rules of personal hygiene and safety precautions provided for when working with drugs.