Metronidazole (Monograph)

Brand name: Flagyl
Drug class: Nitroimidazole Derivatives, Miscellaneous
- Antiprotozoal Agents

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Warning

Carcinogenic in mice and rats.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵
Avoid unnecessary use; reserve for use in approved indications..¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ (See Uses.)

Introduction

Antibacterial and antiprotozoal;.¹⁵² ¹⁹⁷ ⁴³⁰ ⁴⁹⁴ ⁴⁹⁵ nitroimidazole derivative.⁴⁹⁴

Uses for Metronidazole

Bone and Joint Infections

Adjunct for treatment of bone and joint infections caused by Bacteroides, including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus).¹⁵² ¹⁹⁷ ⁴⁹⁵

Endocarditis

Treatment of endocarditis caused by Bacteroides (including the B. fragilis group).¹⁵² ¹⁹⁷ ⁴⁹⁵

Gynecologic Infections

Treatment of gynecologic infections (including endometritis, endomyometritis, tubo-ovarian abscess, postsurgical vaginal cuff infection) caused by Bacteroides (including the B. fragilis group), Clostridium, Peptococcus niger, or Peptostreptococcus.¹⁵² ¹⁹⁷ ⁴⁹⁵

Treatment of acute pelvic inflammatory disease (PID); used in conjunction with other anti-infectives.¹⁹⁹ ³⁴¹ ⁴⁹⁶ Metronidazole is included in PID regimens to provide coverage against anaerobes.³⁴¹

When a parenteral regimen is indicated for PID, an initial regimen of IV cefoxitin and IV or oral doxycycline is recommended followed by oral doxycycline; if tubo-ovarian abscess is present, some experts recommend that the oral follow-up regimen include metronidazole (or clindamycin) in addition to doxycycline.³⁴¹

When an oral regimen is indicated for PID, an single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime is recommended in conjunction with oral doxycycline (with or without oral metronidazole).¹⁹⁹ ³⁴¹ ⁴⁹⁶ Alternatively, if a parenteral cephalosporin is not feasible and the community prevalence and individual risk for gonorrhea is low, a regimen of oral levofloxacin or oral ofloxacin (with or without oral metronidazole) may be considered.⁴⁹⁶

Intra-abdominal Infections

Treatment of intra-abdominal infections (including peritonitis, intra-abdominal abscess, liver abscess) caused by susceptible Bacteroides (including the B. fragilis group), Clostrium, Eubacterium, P. niger, or Peptostreptococcus.¹⁵² ¹⁹⁷ ⁴⁹⁵

Meningitis and Other CNS Infections

Treatment of CNS infections (including meningitis, brain abscess) caused by Bacteroides (including the B. fragilis group).¹⁵² ¹⁹⁷ ⁴⁹⁵

Respiratory Tract Infections

Treatment of respiratory tract infections (including pneumonia) caused by Bacteroides (including the B. fragilis group).¹⁵² ¹⁹⁷ ⁴⁹⁵

Septicemia

Treatment of septicemia caused by Bacteroides (including the B. fragilis group) or Clostridium.¹⁵² ¹⁹⁷ ⁴⁹⁵

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by Bacteroides (including the B. fragilis group), Clostridium, Fusobacterium, P. niger, or Peptostreptococcus.¹⁵² ¹⁹⁷ ⁴⁹⁵

Amebiasis

Treatment of acute intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica.¹⁰⁰ ¹⁵² ¹⁵³ ¹⁹⁷ ³⁶⁴ ³⁶⁸ ³⁷⁰ Oral metronidazole or oral tinidazole followed by a luminal amebicide (iodoquinol, paromomycin) is the regimen of choice for mild to moderate or severe intestinal disease and for amebic hepatic abscess.¹⁰⁰ ¹⁵³ ³⁶⁴ ³⁶⁸ ³⁷⁰

Bacterial Vaginosis

Treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in pregnant or nonpregnant women.¹⁹⁹ ²⁹² ²⁹⁷ ²⁹⁸ ³⁰² ³⁴¹ ³⁶⁵ ³⁶⁶ ⁴³⁰

CDC recommends treatment of bacterial vaginosis in all symptomatic women (including pregnant women).³⁴¹ In addition, asymptomatic pregnant women at high risk for complications of pregnancy should be screened (preferably at the first prenatal visit) and treatment initiated if needed.³⁴¹

Treatment recommendations for bacterial vaginosis in HIV-infected women are the same as those for women without HIV infection.³⁴¹

Regimens of choice in nonpregnant women are a 7-day regimen of oral metronidazole, a 5-day regimen of intravaginal metronidazole gel, or a 7-day regimen of intravaginal clindamycin cream;³⁴¹ alternative regimens are a 7-day regimen of oral clindamycin or 3-day regimen of intravaginal clindamycin suppositories.³⁴¹ The preferred regimens for pregnant women are a 7-day regimen of oral metronidazole or a 7-day regimen of oral clindamycin.³⁴¹

Regardless of regimen used, relapse or recurrence is common;²⁸⁷ ²⁹⁵ ²⁹⁷ ²⁹⁸ ³⁰⁰ ³⁰² ³⁰⁷ ³⁴¹ ³⁶⁵ an alternative regimen (e.g., topical therapy when oral therapy was used initially) may be used in such situations.²⁹⁷ ³⁴¹

Routine treatment of asymptomatic male sexual contacts of women who have relapsing or recurrent bacterial vaginosis not recommended.³⁴¹

Balantidiasis

Alternative to tetracycline for treatment of balantidiasis^{† [off-label]} caused by Balantidium coli.¹⁰⁰ ¹⁵³

Blastocystis hominis Infections

Treatment of infections caused by Blastocystis hominis ^{† [off-label]}.¹⁰⁰ ¹⁵³ ³⁶⁸ ³⁷¹ ³⁷² May be effective, but metronidazole resistance may be common.¹⁵³

Clinical importance of B. hominis as a cause of GI pathology is controversial;¹⁰⁰ ¹⁵³ ³⁶⁸ ³⁷¹ ³⁷² unclear when treatment is indicated.¹⁰⁰ ³⁶⁸ ³⁷¹ Some clinicians suggest treatment be reserved for certain individuals (e.g., immunocompromised patients) when symptoms persist and no other pathogen or process is found to explain their GI symptoms.¹⁰⁰ ³⁶⁸

Clostridium difficile-associated Diarrhea and Colitis

Treatment of Clostridium difficile-associated diarrhea and colitis^{† [off-label]} (CDAD; also known as antibiotic-associated diarrhea and colitis, C. difficile diarrhea, C. difficile colitis, and pseudomembranous colitis).¹⁰⁰ ¹²⁵ ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹ ¹³¹ ¹³² ³¹² ³¹³ ³¹⁴ ³¹⁵ ³¹⁶ ³⁴⁴ ³⁴⁵ ⁴⁴³ ⁴⁴⁴ ⁴⁴⁵ ⁴⁴⁶ ⁴⁴⁷

Drugs of choice are metronidazole and vancomycin; ¹⁰⁰ ³¹² ³¹³ ³¹⁴ ³¹⁵ ³¹⁶ metronidazole generally preferred and vancomycin reserved for those with severe or potentially life-threatening colitis, patients in whom metronidazole-resistant C. difficile is suspected, patients in whom metronidazole is contraindicated or not tolerated, or those who do not respond to metronidazole.¹⁰⁰ ¹²⁶ ¹²⁷ ³¹² ³¹³ ³¹⁴ ³¹⁵ ³¹⁶ ³²² ³²³ ⁴⁰⁶ ⁴⁴³ ⁴⁴⁴ ⁴⁴⁵ ⁴⁴⁶ ⁴⁴⁷ ⁴⁴⁸

Crohn’s Disease

Mangement of Crohn’s disease^{† [off-label]} as an adjunct to conventional therapies.¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴

Has been used with⁴⁶⁷ ⁴⁶⁸ ⁴⁷¹ ⁴⁷⁵ ⁴⁷⁶ ⁴⁷⁷ ⁴⁸⁵ or without ciprofloxacin;¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ⁴⁶⁹ ⁴⁷⁰ ⁴⁷¹ ⁴⁷² ⁴⁷³ ⁴⁷⁴ ⁴⁷⁸ ⁴⁷⁹ ⁴⁸⁴ ⁴⁸⁵ ⁴⁸⁶ for induction of remission of mildly to moderately active Crohn’s disease^{† [off-label]}.¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ⁴⁶⁷ ⁴⁶⁸ ⁴⁶⁹ ⁴⁷¹ ⁴⁷² ⁴⁷³ ⁴⁷⁴ ⁴⁷⁵ ⁴⁷⁶ ⁴⁷⁷ ⁴⁷⁸ ⁴⁷⁹ ⁴⁸⁴

Has been used for refractory perianal Crohn’s disease^†.¹⁰² ¹⁰⁴ ¹⁰⁵ ⁴⁷⁰ ⁴⁷¹ ⁴⁷⁴ ⁴⁷⁸ ⁴⁷⁹ ⁴⁸⁵ ⁴⁸⁶

Dientamoeba fragilis Infections

Treatment of infections caused by Dientamoeba fragilis ^†.¹⁵³ Drugs of choice are iodoquinol, paromomycin, tetracycline, or metronidazole.¹⁵³

Dracunculiasis

Treatment of dracunculiasis^† caused by Dracunculus medinensis (guinea worm disease).¹⁵³

Treatment of choice is slow extraction of worm combined with wound care.¹⁵³ Metronidazole is not curative, but decreases inflammation and facilitates worm removal.¹⁵³

Giardiasis

Treatment of giardiasis^†.¹⁰⁰ ¹⁵³ ³⁶⁷ ⁴⁵² Drugs of choice are metronidazole, tinidazole, or nitazoxanide;¹⁰⁰ ¹⁵³ ³⁶⁷ ⁴⁵² alternatives are paromomycin, furazolidone (no longer commercially available in the US), or quinacrine (not commercially available in the US).¹⁰⁰ ¹⁵³ ³⁶⁷

Treatment of asymptomatic carriers of giardiasis^†.¹⁰⁰ ³⁶⁷ Treatment of such carriers not generally recommended, except possibly in patients with hypogammaglobulinemia or cystic fibrosis or in an attempt to prevent household transmission of the disease from toddlers to pregnant women.¹⁰⁰

Helicobacter pylori Infection and Duodenal Ulcer Disease

Treatment of Helicobacter pylori infection and duodenal ulcer disease (active or a history of duodenal ulcer); eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Used in a multiple-drug regimen that includes metronidazole, tetracycline, and bismuth subsalicylate and a histamine H₂-receptor antagonist.⁴⁵⁵ If initial 14-day regimen does not eradicate H. pylori, a retreatment regimen that does not include metronidazole should be used.⁴⁵⁵

Nongonococcal Urethritis

Treatment of recurrent and persistent urethritis^† in patients with nongonococcal urethritis who have already been treated with a recommended regimen (i.e., azithromycin, doxycycline, erythromycin, ofloxacin or levofloxacin).³⁴¹

Oral metronidazole or oral tinidazole used in conjunction with oral azithromycin (if azithromycin was not used in the initial regimen) is the regimen recommended by CDC for recurrent and persistent urethritis in patients who were compliant with their initial regimen and have not been re-exposed.³⁴¹

Rosacea

Treatment of inflammatory lesions (papules and pustules) and erythema associated with rosacea^† (acne rosacea).¹³⁷ ¹³⁹ ¹⁴⁵ ¹⁴⁶ ¹⁴⁸ ¹⁶⁸ ¹⁸⁰ ¹⁸¹ Topical metronidazole may be preferred to oral metronidazole.¹³⁷ ¹⁸¹

Tetanus

Adjunct in treatment of tetanus caused by C. tetani.¹⁰⁰ ⁴⁸⁹

Trichomoniasis

Treatment of symptomatic and asymptomatic trichomoniasis when Trichomonas vaginalis has been demonstrated by an appropriate diagnostic procedure (e.g., wet smear and/or culture, OSOM Trichomonas Rapid Test, Affirm VP III).¹⁰⁰ ¹⁵² ¹⁵³ ¹⁹⁷ ¹⁹⁹ ²⁹⁷ ²⁹⁸ ³⁰² ³³⁷ ³³⁸ ³³⁹ ³⁴¹

Drug of choice is metronidazole or tinidazole.¹⁰⁰ ¹⁵³ ¹⁹⁹ ²⁹⁷ ³⁰² ³³⁷ ³³⁸ ³³⁹ ³⁴¹ Goal of treatment is to provide symptomatic relief, achieve microbiologic cure, and reduce transmission; to achieve this goal, both the index patient and sexual (particularly steady) partner(s) should be treated.¹⁵³ ¹⁹⁹ ²⁹⁷ ³⁰² ³³⁹ ³⁴¹

If treatment failure occurs with initial metronidazole treatment and reinfection is excluded, alternative regimens using metronidazole or tinidazole can be used.¹⁵³ ¹⁹⁹ ³⁴¹ If retreatment is ineffective, consultation with an expert (available through CDC) is recommended.³⁴¹

Perioperative Prophylaxis

Perioperative prophylaxis to reduce the incidence of postoperative anaerobic bacterial infections in patients undergoing colorectal surgery.¹⁰⁹ ¹¹⁰ ¹¹¹ ¹¹² ¹⁵⁶ ⁴⁹⁵ Preferred regimens are IV cefoxitin alone; IV cefazolin and IV metronidazole; oral erythromycin and oral neomycin; or oral metronidazole and oral neomycin.¹¹⁰ ¹¹² ⁴⁹⁰

Perioperative prophylaxis in patients undergoing appendectomy^†;¹⁰⁹ ¹¹¹ ¹¹⁰ ¹¹² ¹¹³ used in conjunction with cefazolin.¹¹⁰ Preferred regimens for appendectomy (nonperforated) are IV cefoxitin alone or IV cefazolin and IV metronidazole.¹¹⁰

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims^†; used in conjunction with IM ceftriaxone and oral azithromycin or doxycycline.¹⁹⁹ ³⁴¹

Metronidazole Dosage and Administration

Administration

Administer orally¹⁵² ¹⁹⁷ ⁴³⁰ or by continuous or intermittent IV infusion.¹⁵⁶ ⁴⁹⁵ Do not administer by rapid IV injection because of the low pH of the reconstituted product.¹⁵⁶ ⁴⁹⁵

In the treatment of serious anaerobic infections, parenteral route usually is used initially and oral metronidazole substituted when warranted by patient’s condition.¹⁵² ¹⁹⁷

Oral Administration

Administer extended-release tablets at least 1 hour before or 2 hours after meals.⁴³⁰

Extemporaneously Compounded Oral Liquid

An extemporaneously compounded oral liquid formulation of metronidazole containing 50 mg/mL has been prepared.⁹⁸

Standardize 4 Safety

Standardized concentrations for an extemporaneously compounded oral liquid formulation of metronidazole have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.⁹⁹ Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.⁹⁹ For additional information on S4S (including updates that may be available), see [Web].⁹⁹

Table 1: Standardize 4 Safety Compounded Oral Liquid Standards for Metronidazole99
Concentration Standards
50 mg/mL

IV Infusion

Commercially available metronidazole injection for IV infusion does not need to be diluted or neutralized prior to IV administration.¹⁵⁶ ⁴⁹⁵

Metronidazole hydrochloride powder for injection must by reconstituted, diluted, and then neutralized prior to IV administration.¹⁵⁶

Reconstitution and Dilution

Reconstitute metronidazole hydrochloride powder for injection by adding 4.4 mL of sterile or bacteriostatic water for injection, 0.9% sodium chloride injection, or bacteriostatic sodium chloride injection to the vial containing 500 mg of metronidazole.¹⁵⁶ The reconstituted solution contains approximately 100 mg of metronidazole/mL and has a pH of 0.5–2.¹⁵⁶

The reconstituted metronidazole hydrochloride solution must be further diluted with 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer’s injection to a concentration of ≤8 mg/mL.¹⁵⁶

The reconstituted and diluted metronidazole hydrochloride solution must then be neutralized by adding approximately 5 mEq of sodium bicarbonate injection for each 500 mg of metronidazole.¹⁵⁶ The addition of sodium bicarbonate to the metronidazole hydrochloride solution may generate carbon dioxide gas and it may be necessary to relieve gas pressure in the container.¹⁵⁶

Rate of Administration

IV infusions usually are infused over 1 hour.¹⁵⁶ ⁴⁹⁵

Dosage

Available as metronidazole¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ and metronidazole hydrochloride;¹⁵⁶ dosage expressed in terms of metronidazole.¹⁵⁶

Pediatric Patients

General Dosage in Neonates†

Oral or IV

Neonates <1 week of age: AAP recommends 7.5 mg/kg every 24–48 hours in those weighing <1.2 kg, 7.5 mg/kg every 24 hours in those weighing 1.2–2 kg, or 7.5 mg/kg every 12 hours in those weighing >2 kg.¹⁰⁰

Neonates 1–4 weeks of age: AAP recommends 7.5 mg/kg every 24–48 hours in those weighing <1.2 kg, 7.5 mg/kg every 12 hours in those weighing 1.2–2 kg, and 15 mg/kg every 12 hours in those weighing >2 kg.¹⁰⁰

General Dosage in Children ≥1 Month of Age†

Oral

15–35 mg/kg daily in 3 divided doses.¹⁰⁰ AAP states oral route inappropriate for severe infections.¹⁰⁰

Amebiasis

Entamoeba histolytica Infections

Oral

35–50 mg/kg daily in 3 divided doses given for 7–10 (usually 10) days;¹⁵² ¹⁵³ ¹⁹⁷ ³⁷⁰ follow-up with a luminal amebicide (e.g., iodoquinol, paromomycin).¹⁵³

Bacterial Vaginosis†

Oral

Children weighing <45 kg: 15 mg/kg daily (up to 1 g) in 2 divided doses given for 7 days.¹⁰⁰

Adolescents: 500 mg twice daily for 7 days.¹⁰⁰

Balantidiasis†

Oral

35–50 mg/kg daily in 3 divided doses given for 5 days.¹⁵³

Blastocystis hominis Infections†

Oral

20–35 mg/kg daily in 3 divided doses given for 10 days may improve symptoms in some patients.¹⁰⁰

Crohn’s Disease†

Oral

10–20 mg/kg daily (up to 1 g daily) has been recommended for children with mild perianal Crohn’s disease^† or those intolerant to sulfasalazine or mesalamine.⁴⁸⁷

Clostridium difficile-associated Diarrhea and Colitis†

Oral

30–50 mg/kg daily in 3 or 4 equally divided doses given for 7–10 days (not to exceed adult dosage).¹⁰⁰ ⁴⁴⁵ ⁴⁴⁶

Dientamoeba fragilis Infections†

Oral

20–40 mg/kg daily in 3 divided doses given for 10 days.¹⁵³

Dracunculiasis†

Oral

25 mg/kg daily (up to 750 mg) in 3 divided doses given for 10 days.¹⁵³ Is not curative, but may decrease inflammation and facilitate worm removal.¹⁵³

Giardiasis†

Oral

15 mg/kg daily in 3 divided doses given for 5–7 days.¹⁵³ ³⁶⁷ ⁴⁵²

Nongonococcal Urethritis†

Oral

Recurrent or persistent urethritis in adolescents: A single 2-g dose given in conjunction with a single 1-g dose of oral azithromycin (if azithromycin not used in the initial regimen).³⁴¹

Tetanus†

Oral

30 mg/kg daily (up to 4 g daily) in 4 doses given for 10–14 days.¹⁰⁰

IV

30 mg/kg daily (up to 4 g daily) in 4 doses given for 10–14 days.¹⁰⁰

Trichomoniasis†

Oral

Prepubertal children weighing <45 kg: 15 mg/kg daily in 3 divided doses (up to 2 g daily) given for 7 days.¹⁰⁰ ¹⁵³

Adolescents: A single 2-g dose or 500 mg twice daily for 7 days.¹⁰⁰

Prophylaxis in Sexual Assault Victims†

Oral

Preadolescent children weighing <45 kg: 15 mg/kg daily given in 3 divided doses for 7 days given in conjunction with IM ceftriaxone and either oral azithromycin or oral erythromycin.¹⁰⁰ ³⁴¹

Adolescents and preadolescent children weighing ≥45 kg: A single 2-g dose given in conjunction with IM ceftriaxone and either oral azithromycin or oral doxycycline.¹⁰⁰ ³⁴¹

Adults

Anaerobic Bacterial Infections

Serious Infections

Oral

7.5 mg/kg every 6 hours (up to 4 g daily).¹⁵² ¹⁵⁶ ¹⁹⁷

IV, then Oral

An initial IV loading dose of 15 mg/kg followed by IV maintenance doses of 7.5 mg/kg every 6 hours.¹⁵⁶ ⁴⁹⁵ After clinical improvement occurs, switch to oral metronidazole (7.5 mg/kg every 6 hours).¹⁵⁶ ⁴⁹⁵

Total duration of treatment usually is 7–10 days, but infections of bone and joints, lower respiratory tract, or endocardium may require longer treatment.¹⁵⁶ ⁴⁹⁵

Gynecologic Infections

Pelvic Inflammatory Disease

Oral

500 mg twice daily given for 14 days; used in conjunction with a single IM dose of ceftriaxone (250 mg), cefoxitin (2 g with oral probenecid 1 g), or another parenteral cephalosporin (e.g., cefotaxime) and 14-day regimen of oral doxycycline (100 mg twice daily).³⁴¹ ⁴⁹⁶

Alternatively, 500 mg twice daily given for 14 days; used in conjunction with a 14-day regimen of oral ofloxacin (400 mg twice daily) or levofloxacin (500 mg once daily).¹⁹⁹ ³⁴¹ ⁴⁹⁶ Regimens containing a fluoroquinolone should only be considered when a parenteral cephalosporin is not feasible and the community prevalence and individual risk of gonorrhea is low.⁴⁹⁶

Amebiasis

Entamoeba histolytica Infections

Oral

750 mg 3 times daily given for 5–10 (usually 10) days for intestinal amebiasis¹⁵² ¹⁵³ ¹⁹⁷ ³⁶⁴ ³⁶⁸ ³⁷⁰ or 500–750 mg 3 times daily given for 5–10 (usually 10) days for amebic liver abscess.¹⁵² ¹⁹⁷ ³⁶⁴ ³⁶⁸ ³⁷⁰ Alternatively, amebic liver abscess has been treated with 2.4 g once daily given for 1 or 2 days.³⁶⁴

Follow-up with a luminal amebicide (e.g., iodoquinol, paromomycin) after metronidazole.¹⁵³ ³⁶⁴ ³⁶⁸ ³⁷⁰

500 mg every 6 hours for 10 days.³⁶⁴

Bacterial Vaginosis

Nonpregnant Women

Oral

Conventional tablets: 500 mg twice daily given for 7 days.¹⁰⁰ ¹⁹⁹ ²⁸⁶ ²⁹⁷ ²⁹⁸ ³⁰⁰ ³⁰¹ ³⁰² ³⁴¹ ³⁶⁶ A single 2-g dose has been used (e.g., for patients who may be noncompliant with the multiple-dose regimen),¹²⁰ ¹²² ¹⁹⁹ ²⁹² ²⁹⁷ but appears to be less effective than other regimens and is no longer recommended by CDC.³⁴¹

Extended-release tablets: 750 mg once daily given for 7 days.¹⁹⁹ ³⁴¹ ⁴¹⁶ ⁴¹⁷ ⁴³⁰

Pregnant Women

Oral

Conventional tablets: 500 mg twice daily or 250 mg 3 times daily given for 7 days.³⁴¹ ⁴¹⁶ ⁴¹⁷

Contraindicated during first trimester of pregnancy.¹⁵² ¹⁹⁷ ⁴³⁰ In addition, single-dose regimens not recommended in pregnant women because of the slightly higher serum concentrations attained, which may reach fetal circulation.¹⁵²

Balantidiasis†

Oral

750 mg 3 times daily given for 5 days.¹⁵³

Blastocystis hominis Infections†

Oral

750 mg 3 times daily given for 10 days may improve symptoms in some patients.¹⁰⁰ ¹⁵³

Crohn’s Disease†

Oral

400 mg twice daily¹⁰¹ ¹⁰³ ¹⁰⁵ or 1 g daily has been effective for treatment of active Crohn’s disease^†.⁴⁶⁷ ⁴⁷² ⁴⁷³ ⁴⁷⁵ ⁴⁷⁶ ⁴⁸² For treatment of refractory perineal disease, 20 mg/kg (1–1.5 g) given in 3–5 divided doses daily has been employed.¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ⁴⁷⁸ ⁴⁸⁶

Clostridium difficile-associated Diarrhea and Colitis†

Oral

750 mg to 2 g daily in 3 or 4 divided doses given for 7–14 days.¹²⁵ ¹²⁶ ¹²⁹ ¹³¹ ¹³² ¹³³ ³¹³ ³¹⁴

Dose-ranging studies to determine comparative efficacy have not been performed; most commonly employed regimens are 250 mg 4 times daily or 500 mg 3 times daily given for 10 days.⁴⁴³ ⁴⁴⁴ ⁴⁴⁵ ⁴⁴⁶

IV

500–750 mg every 6–8 hours; use when oral therapy is not feasible.¹³⁴ ¹⁶¹ ¹⁶² ³¹³ ³⁴² ³⁴³ ⁴⁴⁵

Dientamoeba fragilis Infections†

Oral

500–750 mg 3 times daily given for 10 days.¹⁵³

Dracunculiasis†

Oral

250 mg 3 times daily given for 10 days.¹⁵³ Is not curative, but may decrease inflammation and facilitate worm removal.¹⁵³

Giardiasis†

Oral

250 mg 3 times daily given for 5–7 days.¹⁵³ ³⁶⁷ ⁴⁵²

Helicobacter pylori Infection and Duodenal Ulcer Disease

Oral

250 mg in conjunction with tetracycline (500 mg) and bismuth subsalicylate (525 mg) 4 times daily (at meals and at bedtime) for 14 days; these drugs should be given concomitantly with an H₂-receptor antagonist in recommended dosage.⁴⁵⁵

Nongonococcal Urethritis†

Oral

Recurrent or persistent urethritis: A single 2-g dose given in conjunction with a single 1-g dose of oral azithromycin (if azithromycin not used in the initial regimen).³⁴¹

Tetanus†

IV

500 mg every 6 hours given for 7–10 days.⁴⁸⁹

Trichomoniasis

Initial Treatment

Oral

2 g as a single dose¹⁵² ¹⁵³ ¹⁹⁹ ³⁴¹ or in 2 divided doses.¹⁵² Alternatively, 500 mg twice daily given for 7 days¹⁵³ ¹⁹⁹ ³⁴¹ or 375 mg twice daily given for 7 days.¹⁹⁹ ¹⁹⁷ Manufacturer also recommends 250 mg 3 times daily given for 7 days.¹⁵²

Retreatment

Oral

500 mg twice daily given for 7 days.²⁹⁷ ³⁴¹ If repeated failure occurs, CDC recommends 2 g once daily given for 5 days.²⁹⁷ ³⁴¹ Others recommend retreatment with 2–4 g daily for 7–14 days if metronidazole-resistant strains are involved.¹⁵³ ¹⁹⁹

Do not administer repeat courses of treatment unless presence of T. vaginalis is confirmed by wet smear and/or culture and an interval of 4–6 weeks has passed since the initial course.¹⁵² ¹⁹⁷

If treatment of resistant infection is guided by in vitro susceptibility testing under aerobic conditions, some clinicians recommend that T. vaginalis strains exhibiting low-level resistance (minimum lethal concentration [MLC] <100 mcg/mL) be treated with 2 g daily for 3–5 days, those with moderate (intermediate) resistance (MLC 100–200 mcg/mL) be treated with 2–2.5 g daily for 7–10 days, and those with high-level resistance (MLC >200 mcg/mL) be treated with 3–3.5 g daily for 14–21 days.¹²⁴ ³⁰² ³³⁸ ³⁴⁰ Because strains with high-level resistance are difficult to treat,¹²⁴ ²⁹⁷ ³⁰² ³³⁸ ³⁴⁰ CDC recommends that patients with culture-documented infection who do not respond to repeat regimens at dosages up to 2 g daily for 3–5 days and in whom the possibility of reinfection has been excluded should be managed in consultation with an expert (available through CDC).²⁹⁷ ³⁴¹

Perioperative Prophylaxis

Colorectal Surgery

0.5 g given at induction of anesthesia (within 0.5–1 hour prior to incision); used in conjunction with IV cefazolin (1–2 g).¹¹⁰

Manufacturer recommends 15 mg/kg by IV infusion over 30–60 minutes 1 hour prior to the procedure and, if necessary, 7.5 mg/kg by IV infusion over 30–60 minutes at 6 and 12 hours after the initial dose.¹⁵⁶ ⁴⁹⁵ The initial preoperative dose must be completely infused approximately 1 hour prior to surgery to ensure adequate serum and tissue concentrations of metronidazole at the time of incision.¹⁵⁶ ⁴⁹⁵ Prophylactic use of metronidazole should be limited to the day of surgery and should not be continued for more than 12 hours after surgery.¹⁵⁶ ⁴⁹⁵

Oral

2 g with oral neomycin sulfate (2 g) given at 7 p.m. and 11 p.m. on day before surgery; used in conjunction with appropriate diet and catharsis.¹¹⁰

Prophylaxis in Sexual Assault Victims†

Oral

A single 2-g dose given in conjunction with IM ceftriaxone and either oral azithromycin or oral doxycycline.¹⁰⁰ ³⁴¹

Special Populations

Hepatic Impairment

Decrease dosage in patients with severe hepatic impairment and monitor plasma concentrations of the drug.¹⁵² ¹⁵⁶ ¹⁶⁰ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic function.¹⁵² ¹⁹⁷ ⁴³⁰

Cautions for Metronidazole

Contraindications

Hypersensitivity to metronidazole or other nitroimidazole derivatives.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ Cautious desensitization has been used in some situations when use of metronidazole was considered necessary.³⁴¹ ⁴³⁶ (See Hypersensitivity Reactions and Desensitization under Cautions.)
First trimester of pregnancy.¹⁵² ¹⁹⁷ ⁴³⁰
Helidac Therapy (kit containing tetracycline, metronidazole, bismuth subsalicylate) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, patients with known allergy to aspirin or salicylates, and those with known hypersensitivity to any component of the kit.⁴⁵⁵

Warnings/Precautions

Warnings

Seizures and Peripheral Neuropathy

Seizures and peripheral neuropathy (characterized by numbness or paresthesia of an extremity) reported with metronidazole.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Persistent peripheral neuropathy reported in some patients receiving prolonged therapy.⁴³⁰ If abnormal neurologic signs develop, promptly discontinue drug..¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰

Use with caution in those with CNS diseases.¹⁵² ¹⁹⁷ ⁴³⁰

Sensitivity Reactions

Hypersensitivity Reactions and Desensitization

Hypersensitivity reactions, including urticaria, pruritus, erythematous rash, flushing, nasal congestion, fever, and fleeting joint pains sometimes resembling serum sickness, have been reported with metronidazole.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Because there are no effective alternatives to metronidazole in the US for treatment of trichomoniasis, CDC states that desensitization can be attempted in patients with metronidazole hypersensitivity.³⁴¹ The possibility that desensitization may be hazardous should be considered⁴³⁵ and adequate procedures (e.g., established IV access, BP monitoring) and therapies (e.g., epinephrine, corticosteroids, antihistamines, oxygen) for management of an acute hypersensitivity reaction should be readily available.⁴³⁵ Pretreatment (e.g., with an antihistamine and/or corticosteroid) also should be considered.⁴³⁵

Desensitization has been performed by administering increasing doses of IV metronidazole incrementally until a therapeutic dose was achieved, at which time oral dosing was initiated.⁴³⁵ In this regimen, an initial 5-mcg dose of IV metronidazole was given and the dose increased at 15- to 20-minute intervals to 15, 50, 150, and 500 mcg and then to 1.5, 5, 15, 30, 60, and 125 mg.⁴³⁵ After the 125-mg IV dose, dosing was switched to oral metronidazole and doses of 250, 500, and 2 g were given at 1-hour intervals.⁴³⁵ For trichomoniasis, desensitization dosing can be stopped after the 2-g dose.⁴³⁵ Patient should be monitored for ≥4 hours after the last dose (24 hours if there was any evidence of a reaction).⁴³⁵

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of metronidazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹⁵² ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹⁵² ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹⁵² ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Surgical procedures should be performed in conjunction with metronidazole therapy when indicated.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

In mixed aerobic and anaerobic infections, anti-infectives appropriate for treatment of aerobic bacteria should be used in conjunction with metronidazole.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

History of Blood Dyscrasia

Use with caution in patients with evidence or history of blood dyscrasias.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Mild leukopenia has been reported, but persistent hematologic abnormalities do not occur.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Perform total and differential leukocyte counts before and after metronidazole treatment, especially when repeated courses are necessary.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Sodium Content

Metronidazole injection contains approximately 28 mEq of sodium per g of metronidazole.¹⁵⁶ ⁴⁹⁵ Use with caution in patients receiving corticosteroids and in those predisposed to edema.¹⁵⁶ ⁴⁹⁵

Candidiasis

Known or previously unrecognized candidiasis may present more prominent symptoms during metronidazole therapy; treatment with an appropriate antifungal is required.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Helidac Therapy

When the kit containing tetracycline, metronidazole, and bismuth subsalicylate (Helidac Therapy) is used for the treatment of H. pylori infection and duodenal ulcer disease, the cautions, precautions, and contraindications associated with tetracycline and bismuth subsalicylate must be considered in addition to those associated with metronidazole.⁴⁵⁵

Specific Populations

Pregnancy

Category B.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ Contraindicated during the first trimester of pregnancy.¹⁰⁰ ¹⁵² ¹⁹⁷ ³⁴¹ ⁴³⁰ ⁴⁴²

Lactation

Distributed into milk;¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ discontinue nursing or the drug.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

If a single 2-g dose of metronidazole is indicated in the mother, AAP states that breast-feeding should be interrupted for 12–24 hours following the dose.¹⁰⁰

Pediatric Use

Except for oral treatment of amebiasis, safety and efficacy not established in pediatric patients.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Metronidazole has been used and is recommended for use in pediatric patients for various indications other than amebiasis (e.g., trichomoniasis, giardiasis).¹⁰⁰ ¹⁵³ Unusual adverse effects have not been reported in pediatric patients.¹⁰⁰

Safety and efficacy of the kit containing metronidazole, tetracycline, and bismuth subsalicylate (Helidac Therapy) for treatment of H. pylori infection and duodenal ulcer disease have not been established in pediatric patients.⁴⁵⁵

Geriatric Use

Because of age-related decreases in hepatic function, monitor serum metronidazole concentrations and adjust dosage accordingly.¹⁵² ¹⁹⁷ ⁴³⁰

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults to concomitant use of metronidazole, tetracycline, and bismuth subsalicylate (Helidac Therapy) for treatment of H. pylori infection and duodenal ulcer disease.⁴⁵⁵ Age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy should be considered.⁴⁵⁵

Hepatic Impairment

Patients with severe hepatic impairment metabolize metronidazole more slowly, and increased concentrations of the drug and metabolites may occur.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Use with caution, monitor plasma metronidazole concentrations, and reduce dosage in patients with severe hepatic impairment.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Common Adverse Effects

Nausea, headache, anorexia, dry mouth, unpleasant metallic taste.¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Drug Interactions

Specific Drugs

Drug	Interaction	Comments
Alcohol	Mild disulfiram-like reactions (flushing, headache, nausea, vomiting, abdominal cramps, sweating) may occur if alcohol is ingested while receiving metronidazole¹³⁹ ¹⁵² ¹⁵⁶ ¹⁵⁷ ¹⁸⁷ ¹⁹⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵	Alcohol should not be consumed during or for at least 1 day following completion of metronidazole therapy (at least 3 days after oral capsules or extended-release tablets)¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵
Anticoagulants, oral (warfarin)	Prolonged PT¹⁵² ¹⁵⁶ ¹⁹¹ ¹⁹² ¹⁹³ ¹⁹⁴ ¹⁹⁵ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵	Monitor PT and adjust anticoagulant dosage as needed¹⁹¹ ¹⁹² ¹⁹³ ¹⁹⁴ ¹⁹⁵
Cimetidine	Possible prolonged half-life and decreased clearance of metronidazole¹⁰⁶ ¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵	If used concomitantly, consider possibility of increased metronidazole adverse effects¹⁰⁶
Disulfiram	Acute psychoses and confusion with concomitant use¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵	Avoid concomitant use; do not initiate metronidazole therapy until 2 weeks after discontinuance of disulfiram¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵
Lithium	Increased lithium concentrations resulting in lithium toxicity;¹⁵¹ ¹⁵² ¹⁵⁵ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵ renal toxicity (elevated serum creatinine, hypernatremia, abnormally dilute urine) reported¹⁵¹	Use concomitantly with caution; monitor serum lithium and creatinine concentrations during concomitant use¹⁵¹ ¹⁵² ¹⁵⁵ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵
Phenobarbital	Decreased serum half-life and increased metabolism of metronidazole¹¹⁶ ¹¹⁷ ¹⁵² ¹⁹⁷ ⁴³⁰ ⁴⁹⁵
Phenytoin	Decrased serum concentration and increased metabolism of metronidazole; decreased clearance of phenytoin¹⁵² ¹⁵⁶ ¹⁹⁷ ⁴³⁰ ⁴⁹⁵

Metronidazole Pharmacokinetics

Absorption

Bioavailability

≥80% of an oral dose is absorbed from the GI tract.^g Following oral administration of conventional tablets or capsules, peak plasma concentrations of unchanged drug and active metabolites attained within 1–3 hours.^g

Following oral administration of metronidazole extended-release tablets for 7 consecutive days under fasting conditions, steady-state peak plasma concentrations attained an average of 6.8 hours after the dose.⁴³⁰

Food

Conventional tablets or capsules: Food decreases the rate of absorption and peak plasma concentrations; total amount of drug not affected.^g

Extended-release tablets: Food increases rate of absorption and peak plasma concentrations.⁴³⁰

Distribution

Extent

Widely distributed into most body tissues and fluids, including bone, bile, saliva, pleural fluid, peritoneal fluid, vaginal secretions, seminal fluid, and cerebral and hepatic abscesses.^g

Distributed into CSF; CSF concentrations are 43% of concurrent plasma concentrations in patients with uninflamed meninges and equal to or greater than concurrent plasma concentrations in patients with inflamed meninges.^g

Readily crosses the placenta and is distributed into milk.^g

Plasma Protein Binding

<20%.^g

Elimination

Metabolism

Approximately 30–60% of an oral or IV dose is metabolized in the liver by hydroxylation, side-chain oxidation, and glucuronide conjugation.^g The major metabolite, 2-hydroxy metronidazole, has some antibacterial and antiprotozoal activity.^g

Elimination Route

Metronidazole and its metabolites are excreted principally in urine (60–80%) and to a lesser extent in feces (6–15%).¹⁵² ¹⁹⁷ ⁴³⁰ ^g

Half-life

Adults with normal renal and hepatic function: 6–8 hours.⁴³⁰ ^g

Special Populations

Half-life may be prolonged in patients with impaired hepatic function.^g In adults with alcoholic liver disease and impaired hepatic function, half-life averages 18.3 hours.¹⁶⁰

Pharmacokinetics not affected by renal impairment.⁴³⁰ ^g

Stability

Storage

Oral

Capsules

15–25°C.¹⁹⁷ Dispense in well-closed container with child-resistant closure.¹⁹⁷

Tablets

Conventional tablets: <25°C.¹⁵²

Extended-release tablets: 25°C (may be exposed to 15–30°C).⁴³⁰ Dispense in well-closed container with child-resistant closure.⁴³⁰

Metronidazole Combinations

Kit containing tetracycline, metronidazole, and bismuth subsalicylate: 20–25°C.⁴⁵⁵

Parenteral

Injection for IV infusion

15–30°C; protect from light.¹⁵⁶ ⁴⁹⁵ Do not refrigerate.¹⁵⁶

Powder for IV infusion

<25°C; protect from light.¹⁵⁶ After reconstitution, dilution, and neutralization, use within 24 hours; do not refrigerate.¹⁵⁶

Actions and Spectrum

Bactericidal, amebicidal, and trichomonacidal in action.^g
Un-ionized at physiologic pH and readily taken up by anaerobic organisms or cells.^g In susceptible organisms or cells, metronidazole is reduced by low-redox-potential electron transport proteins (e.g., nitroreductases such as ferredoxin); the reduction product(s) apparently are responsible for the cytotoxic and antimicrobial effects of the drug (e.g., disruption of DNA, inhibition of nucleic acid synthesis).^g
Has direct anti-inflammatory effects¹³⁷ ¹³⁹ ¹⁴⁸ ¹⁶⁶ ¹⁶⁷ and effects on neutrophil motility, lymphocyte transformation, and some aspects of cell-mediated immunity.¹⁴⁸ ¹⁶⁸ ¹⁶⁹ ¹⁷⁰ ¹⁷¹ ¹⁷²
Spectrum of activity includes most obligately anaerobic bacteria and many protozoa.^g Inactive against fungi and viruses and most aerobic or facultatively anaerobic bacteria.^g
Gram-positive anaerobes: Clostridium,¹⁴⁸ ¹⁵² ¹⁵⁶ ¹⁶⁴ ¹⁷⁴ ¹⁷⁶ C. difficile,¹⁷⁵ ¹⁷⁶ C. perfringens,¹⁶⁴ ¹⁷⁶ Eubacterium,¹⁴⁸ ¹⁵² ¹⁵⁶ ¹⁶⁴ ¹⁷⁴ ¹⁷⁵ Peptococcus,¹⁴⁸ ¹⁵² ¹⁵⁶ ¹⁶⁴ ¹⁷⁴ ¹⁷⁵ ¹⁷⁶ and Peptostreptococcus.¹⁴⁸ ¹⁵² ¹⁵⁶ ¹⁶⁴ ¹⁷⁴ ¹⁷⁶ ¹⁷⁷ ²⁷⁵ ²⁷⁸
Gram-negative anaerobes: Active against Bacteroides fragilis,¹⁴⁸ ¹⁵² ¹⁵⁶ ¹⁶⁴ ¹⁷³ ¹⁷⁴ ¹⁷⁵ ¹⁷⁶ ²⁷⁵ ²⁷⁷ ²⁸⁰ B. distasonis,¹⁵² ¹⁵⁶ ¹⁷⁵ ¹⁷⁶ ²⁷⁵ B. ovatus,¹⁵² ¹⁵⁶ ¹⁷⁶ ²⁷⁵ B. thetaiotaomicron,¹⁵² ¹⁵⁶ ¹⁷⁵ ¹⁷⁶ ²⁷⁵ B. vulgatus,¹⁵² ¹⁵⁶ ¹⁷⁵ ¹⁷⁶ ²⁷⁵ B. ureolyticus,²⁷⁵ ²⁷⁷ Fusobacterium,¹⁴⁸ ¹⁵² ¹⁵⁶ ¹⁶⁴ ¹⁷⁴ ¹⁷⁶ ¹⁷⁷ Prevotella bivia,¹⁷⁴ ²⁷⁵ ²⁷⁷ ²⁷⁸ ²⁷⁹ P. buccae,⁴⁹⁴ P. disiens,¹⁷⁵ ²⁷⁸ P. intermedia,¹⁷⁷ ²⁷⁵ P. melaninogenica,¹⁶⁴ ¹⁷⁵ ²⁷⁵ ²⁷⁷ ²⁷⁸ ²⁷⁹ P. oralis,¹⁷⁵ ²⁷⁵ ²⁷⁷ ²⁷⁹ Porphyromonas,¹⁷⁷ ²⁷⁵ ⁴⁹⁴ and Veillonella.¹⁷⁵ ¹⁷⁶ ¹⁷⁷
Active against Helicobacter pylori,¹⁶⁴ Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia, and Balantidium coli.^g Acts principally against the trophozoite forms of E. histolytica and has limited activity against the encysted form.^g
Resistance has been reported in some Bacteroides and T. vaginalis.^g

Advice to Patients

Advise patients that antibacterials (including metronidazole) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹⁵² ¹⁹⁷ ⁴³⁰
Importance of completing full course of therapy, even if feeling better after a few days.¹⁵² ¹⁹⁷ ⁴³⁰
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with metronidazole or other antibacterials in the future.¹⁵² ¹⁹⁷ ⁴³⁰
Metronidazole extended-release tablets should be taken at least 1 hour before or 2 hours after meals; optimum absorption occurs under fasting conditions.⁴³⁰
Advise patients to avoid alcohol during and for at least 1 day after conventional tablets¹⁵² or at least 3 days after receiving metronidazole capsules or extended-release tablets.¹⁹⁷ ⁴³⁰
Advise patients to promptly discontinue metronidazole and contact clinician if abnormal neurologic signs occur.¹⁵² ¹⁹⁷ ⁴³⁰
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.¹⁵² ¹⁹⁷ ⁴³⁰
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹⁵² ¹⁹⁷ ⁴³⁰
Importance of advising patients of other important precautionary information.¹⁵² ¹⁹⁷ ⁴³⁰ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

metroNIDAZOLE
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	375 mg	Flagyl 375	Pfizer
	Tablets	250 mg*	metroNIDAZOLE Tablets	Mutual
		500 mg*	metroNIDAZOLE Tablets	Mutual
	Tablets, extended-release, film-coated	750 mg	Flagyl ER	Pfizer
	Tablets, film-coated	250 mg*	Flagyl	Pfizer
		500 mg*	Flagyl	Pfizer
Parenteral	Injection, for IV infusion only	5 mg/mL*	Flagyl I.V. RTU (Viaflex [Baxter])	SCS Pharmaceuticals
			metroNIDAZOLE Injection (PAB [Braun])	Various Manufacturers
			metroNIDAZOLE Injection (available in LifeCare and glass containers)	Abbott
			metroNIDAZOLE Injection RTU (Viaflex [Baxter])	Various Manufacturers

metroNIDAZOLE Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Kit	4 Capsules, Tetracycline Hydrochloride 500 mg 4 Tablets, Metronidazole 250 mg (with povidone) 8 Tablets, chewable, Bismuth Subsalicylate 262.4 mg (with povidone)	Helidac Therapy (available as 14 blister cards)	Prometheus

metroNIDAZOLE Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infusion only	500 mg (of metronidazole)	Flagyl I.V. (with mannitol 415 mg)	SCS Pharmaceuticals

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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