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metroNIDAZOLE (Systemic)

Class: Antiprotozoals, Miscellaneous
- Antiprotozoal Agents
VA Class: AM900
CAS Number: 443-48-1
Brands: Flagyl

Medically reviewed by Drugs.com on June 22, 2020. Written by ASHP.

Warning

  • Carcinogenic in mice and rats.

  • Avoid unnecessary use; reserve for use in approved indications.. (See Uses.)

Introduction

Antibacterial and antiprotozoal;. nitroimidazole derivative.

Uses for metroNIDAZOLE (Systemic)

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).

Endocarditis

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

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.

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

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.

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). 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.

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.

Meningitis and Other CNS Infections

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

Respiratory Tract Infections

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

Septicemia

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

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.

Amebiasis

Treatment of acute intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica. 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.

Bacterial Vaginosis

Treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in pregnant or nonpregnant women.

CDC recommends treatment of bacterial vaginosis in all symptomatic women (including pregnant women). 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.

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

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; alternative regimens are a 7-day regimen of oral clindamycin or 3-day regimen of intravaginal clindamycin suppositories. The preferred regimens for pregnant women are a 7-day regimen of oral metronidazole or a 7-day regimen of oral clindamycin.

Regardless of regimen used, relapse or recurrence is common; an alternative regimen (e.g., topical therapy when oral therapy was used initially) may be used in such situations.

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

Balantidiasis

Alternative to tetracycline for treatment of balantidiasis caused by Balantidium coli.

Blastocystis hominis Infections

Treatment of infections caused by Blastocystis hominis. May be effective, but metronidazole resistance may be common.

Clinical importance of B. hominis as a cause of GI pathology is controversial; unclear when treatment is indicated. 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.

Clostridium difficile-associated Diarrhea and Colitis

Treatment of Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis, C. difficile diarrhea, C. difficile colitis, and pseudomembranous colitis).

Drugs of choice are metronidazole and vancomycin; 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.

Crohn’s Disease

Mangement of Crohn’s disease as an adjunct to conventional therapies.

Has been used with or without ciprofloxacin; for induction of remission of mildly to moderately active Crohn’s disease.

Has been used for refractory perianal Crohn’s disease.

Dientamoeba fragilis Infections

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

Dracunculiasis

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

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

Giardiasis

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

Treatment of asymptomatic carriers of giardiasis. 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.

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. If initial 14-day regimen does not eradicate H. pylori, a retreatment regimen that does not include metronidazole should be used.

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).

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.

Rosacea

Treatment of inflammatory lesions (papules and pustules) and erythema associated with rosacea (acne rosacea). Topical metronidazole may be preferred to oral metronidazole.

Tetanus

Adjunct in treatment of tetanus caused by C. tetani.

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).

Drug of choice is metronidazole or tinidazole. 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.

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

Perioperative Prophylaxis

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

Perioperative prophylaxis in patients undergoing appendectomy; used in conjunction with cefazolin. Preferred regimens for appendectomy (nonperforated) are IV cefoxitin alone or IV cefazolin and IV metronidazole.

Prophylaxis in Sexual Assault Victims

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

metroNIDAZOLE (Systemic) Dosage and Administration

Administration

Administer orally or by continuous or intermittent IV infusion. Do not administer by rapid IV injection because of the low pH of the reconstituted product.

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

Oral Administration

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

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

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

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

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. The reconstituted solution contains approximately 100 mg of metronidazole/mL and has a pH of 0.5–2.

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.

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. 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.

Rate of Administration

IV infusions usually are infused over 1 hour.

Dosage

Available as metronidazole and metronidazole hydrochloride; dosage expressed in terms of metronidazole.

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.

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.

General Dosage in Children ≥1 Month of Age†
Oral

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

Amebiasis
Entamoeba histolytica Infections
Oral

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

Bacterial Vaginosis†
Oral

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

Adolescents: 500 mg twice daily for 7 days.

Balantidiasis†
Oral

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

Blastocystis hominis Infections†
Oral

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

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.

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).

Dientamoeba fragilis Infections†
Oral

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

Dracunculiasis†
Oral

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

Giardiasis†
Oral

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

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).

Tetanus†
Oral

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

IV

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

Trichomoniasis†
Oral

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

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

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.

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.

Adults

Anaerobic Bacterial Infections
Serious Infections
Oral

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

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. After clinical improvement occurs, switch to oral metronidazole (7.5 mg/kg every 6 hours).

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

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).

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). 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.

Amebiasis
Entamoeba histolytica Infections
Oral

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

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

IV

500 mg every 6 hours for 10 days.

Bacterial Vaginosis
Nonpregnant Women
Oral

Conventional tablets: 500 mg twice daily given for 7 days. A single 2-g dose has been used (e.g., for patients who may be noncompliant with the multiple-dose regimen), but appears to be less effective than other regimens and is no longer recommended by CDC.

Extended-release tablets: 750 mg once daily given for 7 days.

Pregnant Women
Oral

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

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

Balantidiasis†
Oral

750 mg 3 times daily given for 5 days.

Blastocystis hominis Infections†
Oral

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

Crohn’s Disease†
Oral

400 mg twice daily or 1 g daily has been effective for treatment of active Crohn’s disease. For treatment of refractory perineal disease, 20 mg/kg (1–1.5 g) given in 3–5 divided doses daily has been employed.

Clostridium difficile-associated Diarrhea and Colitis†
Oral

750 mg to 2 g daily in 3 or 4 divided doses given for 7–14 days.

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.

IV

500–750 mg every 6–8 hours; use when oral therapy is not feasible.

Dientamoeba fragilis Infections†
Oral

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

Dracunculiasis†
Oral

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

Giardiasis†
Oral

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

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.

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).

Tetanus†
IV

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

Trichomoniasis
Initial Treatment
Oral

2 g as a single dose or in 2 divided doses. Alternatively, 500 mg twice daily given for 7 days or 375 mg twice daily given for 7 days. Manufacturer also recommends 250 mg 3 times daily given for 7 days.

Retreatment
Oral

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

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.

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. Because strains with high-level resistance are difficult to treat, 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).

Perioperative Prophylaxis
Colorectal Surgery
IV

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).

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. 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. Prophylactic use of metronidazole should be limited to the day of surgery and should not be continued for more than 12 hours after surgery.

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.

Prophylaxis in Sexual Assault Victims†
Oral

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

Special Populations

Hepatic Impairment

Decrease dosage in patients with severe hepatic impairment and monitor plasma concentrations of the drug.

Geriatric Patients

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

Cautions for metroNIDAZOLE (Systemic)

Contraindications

  • Hypersensitivity to metronidazole or other nitroimidazole derivatives. Cautious desensitization has been used in some situations when use of metronidazole was considered necessary. (See Hypersensitivity Reactions and Desensitization under Cautions.)

  • First trimester of pregnancy.

  • 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.

Warnings/Precautions

Warnings

Seizures and Peripheral Neuropathy

Seizures and peripheral neuropathy (characterized by numbness or paresthesia of an extremity) reported with metronidazole.

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

Use with caution in those with CNS diseases.

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.

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. The possibility that desensitization may be hazardous should be considered 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. Pretreatment (e.g., with an antihistamine and/or corticosteroid) also should be considered.

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. 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. 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. For trichomoniasis, desensitization dosing can be stopped after the 2-g dose. Patient should be monitored for ≥4 hours after the last dose (24 hours if there was any evidence of a reaction).

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.

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

Surgical procedures should be performed in conjunction with metronidazole therapy when indicated.

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

History of Blood Dyscrasia

Use with caution in patients with evidence or history of blood dyscrasias.

Mild leukopenia has been reported, but persistent hematologic abnormalities do not occur.

Perform total and differential leukocyte counts before and after metronidazole treatment, especially when repeated courses are necessary.

Sodium Content

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

Candidiasis

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

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.

Specific Populations

Pregnancy

Category B. Contraindicated during the first trimester of pregnancy.

Lactation

Distributed into milk; discontinue nursing or the drug.

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.

Pediatric Use

Except for oral treatment of amebiasis, safety and efficacy not established in pediatric patients.

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

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.

Geriatric Use

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

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. Age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy should be considered.

Hepatic Impairment

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

Use with caution, monitor plasma metronidazole concentrations, and reduce dosage in patients with severe hepatic impairment.

Common Adverse Effects

Nausea, headache, anorexia, dry mouth, unpleasant metallic taste.

Interactions for metroNIDAZOLE (Systemic)

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 metronidazole

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)

Anticoagulants, oral (warfarin)

Prolonged PT

Monitor PT and adjust anticoagulant dosage as needed

Cimetidine

Possible prolonged half-life and decreased clearance of metronidazole

If used concomitantly, consider possibility of increased metronidazole adverse effects

Disulfiram

Acute psychoses and confusion with concomitant use

Avoid concomitant use; do not initiate metronidazole therapy until 2 weeks after discontinuance of disulfiram

Lithium

Increased lithium concentrations resulting in lithium toxicity; renal toxicity (elevated serum creatinine, hypernatremia, abnormally dilute urine) reported

Use concomitantly with caution; monitor serum lithium and creatinine concentrations during concomitant use

Phenobarbital

Decreased serum half-life and increased metabolism of metronidazole

Phenytoin

Decrased serum concentration and increased metabolism of metronidazole; decreased clearance of phenytoin

metroNIDAZOLE (Systemic) Pharmacokinetics

Absorption

Bioavailability

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

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.

Food

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

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

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.

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.

Readily crosses the placenta and is distributed into milk.

Plasma Protein Binding

<20%.

Elimination

Metabolism

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

Elimination Route

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

Half-life

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

Special Populations

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

Pharmacokinetics not affected by renal impairment.

Stability

Storage

Oral

Capsules

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

Tablets

Conventional tablets: <25°C.

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

Metronidazole Combinations

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

Parenteral

Injection for IV infusion

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

Powder for IV infusion

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

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Drug Compatibility (Metronidazole)

Admixture Compatibilitya

Compatible

Amikacin sulfate

Cefazolin sodium

Cefotaxime sodium

Ceftazidime

Ceftizoxime sodium

Ceftriaxone sodium

Cefuroxime sodium

Chloramphenicol sodium succinate

Ciprofloxacin

Clindamycin phosphate

Fluconazole

Gentamicin sulfate

Midazolam HCl

Tobramycin sulfate

Incompatible

Amoxicillin sodium–clavulanate potassium

Aztreonam

Variable

Ampicillin sodium

Cefepime HCl

Cefoxitin sodium

Hydrocortisone sodium succinate

Penicillin G potassium

Y-Site Compatibilitya

Compatible

Acyclovir sodium

Allopurinol sodium

Amifostine

Bivalirudin

Cefepime HCl

Cisatracurium besylate

Clarithromycin

Cyclophosphamide

Dexmedetomidine HCl

Diltiazem HCl

Dimenhydrinate

Docetaxel

Dopamine HCl

Doxapram HCl

Doxorubicin HCl liposome injection

Enalaprilat

Esmolol HCl

Etoposide phosphate

Fenoldopam mesylate

Fluconazole

Foscarnet sodium

Gatifloxacin

Gemcitabine HCl

Granisetron HCl

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCl

Labetalol HCl

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Meperidine HCl

Methylprednisolone sodium succinate

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Perphenazine

Piperacillin sodium–tazobactam sodium

Remifentanil HCl

Sargramostim

Tacrolimus

Teniposide

Theophylline

Thiotepa

Vinorelbine tartrate

Incompatible

Amphotericin B cholesteryl sulfate complex

Aztreonam

Drotrecogin alfa (activated)

Filgrastim

Lansoprazole

Pantoprazole sodium

Pemetrexed disodium

Metronidazole HCla

Solution Compatibility

Incompatible

Amino acids 10%

Drug Compatibility (Metronidazole HCl)
Admixture Compatibilitya

Compatible

Amikacin sulfate

Aminophylline

Cefazolin sodium

Cefotaxime sodium

Cefoxitin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Disopyramide phosphate

Gentamicin sulfate

Heparin sodium

Hydrocortisone sodium succinate

Multielectrolyte concentrate

Multivitamins

Penicillin G potassium

Tobramycin sulfate

Incompatible

Ciprofloxacin

Dopamine HCl

Meropenem

Variable

Ampicillin sodium

Cefepime HCl

Ceftriaxone sodium

Y-Site Compatibilitya

Compatible

Amiodarone HCl

Diltiazem HCl

Incompatible

Meropenem

Warfarin sodium

Actions and Spectrum

  • Bactericidal, amebicidal, and trichomonacidal in action.

  • Un-ionized at physiologic pH and readily taken up by anaerobic organisms or cells. 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).

  • Has direct anti-inflammatory effects and effects on neutrophil motility, lymphocyte transformation, and some aspects of cell-mediated immunity.

  • Spectrum of activity includes most obligately anaerobic bacteria and many protozoa. Inactive against fungi and viruses and most aerobic or facultatively anaerobic bacteria.

  • Gram-positive anaerobes: Clostridium, C. difficile, C. perfringens, Eubacterium, Peptococcus, and Peptostreptococcus.

  • Gram-negative anaerobes: Active against Bacteroides fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus, B. ureolyticus, Fusobacterium, Prevotella bivia, P. buccae, P. disiens, P. intermedia, P. melaninogenica, P. oralis, Porphyromonas, and Veillonella.

  • Active against Helicobacter pylori, Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia, and Balantidium coli. Acts principally against the trophozoite forms of E. histolytica and has limited activity against the encysted form.

  • Resistance has been reported in some Bacteroides and T. vaginalis.

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).

  • Importance of completing full course of therapy, even if feeling better after a few days.

  • 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.

  • Metronidazole extended-release tablets should be taken at least 1 hour before or 2 hours after meals; optimum absorption occurs under fasting conditions.

  • Advise patients to avoid alcohol during and for at least 1 day after conventional tablets or at least 3 days after receiving metronidazole capsules or extended-release tablets.

  • Advise patients to promptly discontinue metronidazole and contact clinician if abnormal neurologic signs occur.

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

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, Teva

500 mg*

metroNIDAZOLE Tablets

Mutual, Teva

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

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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