Metronidazole Dosage

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Usual Adult Dose for Bacterial Infection

Serious anaerobic infections:
IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.

Approved indications: For the treatment of serious infections due to susceptible anaerobic bacteria; such infections include intraabdominal infections (including peritonitis, intraabdominal abscess, liver abscess), skin and skin structure infections, gynecologic infections (including endometritis, endomyometritis, tuboovarian abscess, postsurgical vaginal cuff infection), bacterial septicemia, bone and joint infections (as adjunctive therapy), CNS infections (including meningitis, brain abscess), lower respiratory tract infections (including pneumonia, empyema, lung abscess), and endocarditis

Usual Adult Dose for Amebiasis

Acute intestinal amebiasis (acute amebic dysentery): 750 mg orally 3 times a day for 5 to 10 days
Amebic liver abscess: 500 to 750 mg orally 3 times a day for 5 to 10 days

Comments:
-Aspiration or drainage of pus is still needed for amebic liver abscess.

Some experts recommend:
Mild to moderate intestinal disease: 500 to 750 mg orally 3 times a day for 7 to 10 days
Severe intestinal and extraintestinal disease: 750 mg orally 3 times a day for 7 to 10 days

Usual Adult Dose for Pseudomembranous Colitis

(Not approved by FDA)

Mild to moderate Clostridium difficile infection (CDI): 500 mg orally 3 times a day
Severe, complicated CDI: 500 mg IV every 8 hours
Duration of therapy: 10 days

Comments:
-Metronidazole is the drug of choice for initial episode of mild to moderate CDI.
-Vancomycin (oral or rectal) with or without IV metronidazole is the regimen of choice for initial episode of severe, complicated CDI.
-Metronidazole should not be used beyond the first recurrence of CDI or for long-term chronic therapy due to possible neurotoxicity.

Usual Adult Dose for Surgical Prophylaxis

Initial preoperative dose: 15 mg/kg IV infused over 30 to 60 minutes and completed about 1 hour before surgery
Intraoperative/postoperative dose: 7.5 mg/kg IV infused over 30 to 60 minutes at 6 and 12 hours after the initial dose

Comments:
-Should be administered, if needed, at 6-hour intervals to maintain effective drug levels
-Prophylactic use of metronidazole should be stopped within 12 hours after surgery.

Approved indication: For surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery

Usual Adult Dose for Trichomoniasis

1-day regimen: 2 g orally as a single dose (or as 1 g twice on the same day)

7-day regimen:
Tablets: 250 mg orally 3 times a day for 7 consecutive days
Capsules: 375 mg orally twice a day for 7 consecutive days

Comments:
-The dose regimen should be individualized in females and males; some patients may tolerate 1 regimen more than the other.
-The patient's sexual partner(s) should also be evaluated/treated.
-Some studies indicate the 7-day regimen may have higher cure rates (according to vaginal smears, signs/symptoms) than the 1-day regimen.
-Single-dose therapy can assure compliance (especially if supervised) if cannot rely on patient to complete the 7-day regimen.
-A 7-day regimen may minimize reinfection by protecting patient long enough for sexual partner(s) to get appropriate treatment.
-Pregnant patients should not be treated during the first trimester; if alternative therapy was not adequate in a pregnant patient, the 1-day regimen is not recommended (results in higher serum levels which can reach fetal circulation).
-When repeat courses are needed, an interval of 4 to 6 weeks between courses and reconfirmation of Trichomonas vaginalis by appropriate laboratory testing are recommended; total and differential leukocyte counts recommended before and after retreatment.
-T vaginalis can interfere with abnormal cytological smear assessment; additional smears recommended after parasite eradication.
-Individual decision whether to treat asymptomatic male partners with negative/no cultures; a woman may become reinfected if her sexual partner is not treated; since isolating T vaginalis from asymptomatic male carriers can be considerably difficult, negative smears and cultures cannot be relied upon.
-Sexual partner(s) should be treated with metronidazole in cases of reinfection.

Approved indications:
-Symptomatic trichomoniasis: For the treatment of Trichomonas vaginalis infection in females and males when confirmed by appropriate laboratory procedures (wet smears and/or cultures)
-Asymptomatic trichomoniasis: For the treatment of asymptomatic T vaginalis infection in females when associated with endocervicitis, cervicitis, or cervical erosion
-Treatment of asymptomatic sexual partners: For the simultaneous treatment of asymptomatic sexual partners of treated patients if T vaginalis is present to prevent reinfection of the partner

CDC recommendations:
Recommended regimen: 2 g orally as a single dose
Alternative regimen: 500 mg orally twice a day for 7 days

Comments:
-If treatment failure occurs with single-dose therapy and reinfection is excluded, 500 mg orally twice a day for 7 days is recommended; for patients failing this regimen, 2 g orally for 5 days should be considered.
-Sexual partner(s) should be treated simultaneously with the same dose; appropriate treatment of sexual partner(s) may increase reported cure rates.
-Male partners of women who fail nitroimidazole therapy should be evaluated and treated with 500 mg orally twice a day for 7 days.
-Women can be treated with 2 g orally as a single dose at any stage of pregnancy.
-In women coinfected with trichomoniasis and HIV, single-dose therapy was not as effective as 500 mg orally twice a day for 7 days; this 7-day regimen should be considered for HIV-infected women.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Helicobacter pylori Infection

Some experts recommend:
Bismuth quadruple therapy: 250 mg orally 4 times a day
Clarithromycin-based triple therapy: 500 mg orally twice a day
Duration of therapy: 10 to 14 days

Comments:
-Bismuth quadruple therapy is one recommended primary therapy; includes (a proton pump inhibitor [PPI] or histamine-2 receptor antagonist), bismuth, metronidazole, and tetracycline.
-Clarithromycin-based triple therapy is another recommended primary therapy; includes a PPI, clarithromycin, and (amoxicillin or metronidazole).

Usual Adult Dose for Pelvic Inflammatory Disease

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-The patient's sexual partner(s) should also be evaluated/treated.

Approved indications: For the treatment of serious gynecologic infections (including endometritis, tuboovarian abscess) due to susceptible anaerobic bacteria

CDC recommendations:
Mild to moderately severe acute pelvic inflammatory disease (PID): 500 mg orally twice a day for 14 days

Comments:
-Recommended regimens for outpatient, oral therapy include ceftriaxone plus doxycycline with or without metronidazole, cefoxitin/probenecid plus doxycycline with or without metronidazole, or other parenteral third-generation cephalosporin plus doxycycline with or without metronidazole.
-Since anaerobic organisms are suspected in the etiology of PID, the addition of metronidazole should be considered; also, metronidazole effectively treats bacterial vaginosis, which is often associated with PID.
-When tuboovarian abscess is present, metronidazole with doxycycline is recommended for continued therapy; provides more effective anaerobic coverage than doxycycline alone.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Bacterial Vaginosis

Extended-release tablets: 750 mg orally once a day for 7 consecutive days

Comments:
-The patient's sexual partner(s) should also be evaluated/treated.
-Extended-release tablets should be taken at least 1 hour before or 2 hours after meals (under fasting conditions).
-Extended-release tablets should not be split, chewed, or crushed.

Approved indication: For the treatment of bacterial vaginosis in nonpregnant women

CDC recommendations:
Nonpregnant women:
Immediate-release tablets (recommended regimen): 500 mg orally every 12 hours for 7 days
Extended-release tablets (alternative regimen): 750 mg orally once a day for 7 days

Pregnant women:
Immediate-release tablets: 500 mg orally twice a day for 7 days or 250 mg orally 3 times a day for 7 days

Comments:
-Treatment is recommended for all women with symptoms.

Usual Adult Dose for Aspiration Pneumonia

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Infections of the lower respiratory tract may require longer treatment.
-IV therapy should be continued until the clinical condition stabilizes and fever subsides then oral therapy may be substituted.
-Therapy of documented anaerobic pleuropulmonary infections should be continued until the infiltrate is cleared or a residual scar forms, sometimes for as long as 2 to 4 months.

Approved indications: For the treatment of serious lower respiratory tract infections due to susceptible anaerobic bacteria

Usual Adult Dose for Bacteremia

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.

Approved indications: For the treatment of serious infections due to susceptible anaerobic bacteria; such infections include bacterial septicemia and CNS infections (including meningitis)

Usual Adult Dose for Meningitis

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.

Approved indications: For the treatment of serious infections due to susceptible anaerobic bacteria; such infections include bacterial septicemia and CNS infections (including meningitis)

Usual Adult Dose for Diverticulitis

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.

Approved indications: For the treatment of serious intraabdominal infections (including peritonitis, intraabdominal abscess, liver abscess) due to susceptible anaerobic bacteria

Usual Adult Dose for Intraabdominal Infection

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.

Approved indications: For the treatment of serious intraabdominal infections (including peritonitis, intraabdominal abscess, liver abscess) due to susceptible anaerobic bacteria

Usual Adult Dose for Peritonitis

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.

Approved indications: For the treatment of serious intraabdominal infections (including peritonitis, intraabdominal abscess, liver abscess) due to susceptible anaerobic bacteria

Usual Adult Dose for Endocarditis

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Infections of the endocardium may require longer treatment; about 4 to 6 weeks has been recommended.

Approved indications: For the treatment of serious infections (such as endocarditis) due to susceptible anaerobic bacteria

Usual Adult Dose for Joint Infection

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Infections of the joint may require longer treatment; approximately 3 to 4 weeks or longer therapy (6 weeks or more; for prosthetic joint infections) has been recommended.

Approved indications: For the treatment of serious joint infections (as adjunctive therapy) due to susceptible anaerobic bacteria

Usual Adult Dose for Osteomyelitis

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Infections of the joint may require longer treatment; about 4 to 6 weeks has been recommended; chronic osteomyelitis may require an additional 1 to 2 months of antibiotic therapy.

Approved indications: For the treatment of serious bone infections (as adjunctive therapy) due to susceptible anaerobic bacteria

Usual Adult Dose for Pneumonia

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Infections of the lower respiratory tract may require longer treatment; up to 21 days has been recommended.

Approved indications: For the treatment of serious lower respiratory tract infections (including pneumonia) due to susceptible anaerobic bacteria

Usual Adult Dose for Skin or Soft Tissue Infection

IV:
Loading dose: 15 mg/kg IV
Maintenance dose: 7.5 mg/kg IV every 6 hours

Oral: 7.5 mg/kg orally every 6 hours

Maximum dose: 4 g per day
Usual duration of therapy: 7 to 10 days

Comments:
-IV metronidazole should be infused over 1 hour.
-The first IV maintenance dose should be started 6 hours after the start of the loading dose.
-Some experts recommend continuing therapy for 3 days after resolution of acute inflammation; for more severe infections (such as diabetic soft tissue infections) 14 to 21 days of therapy may be required.

Approved indications: For the treatment of serious skin and skin structure infections due to susceptible anaerobic bacteria

Usual Adult Dose for Giardiasis

(Not approved by FDA)

Some experts recommend: 250 mg orally 3 times a day for 5 to 7 days

Usual Adult Dose for STD Prophylaxis

(Not approved by FDA)

CDC recommendations:
Prophylaxis after sexual assault: 2 g orally as a single dose

Comments:
-Metronidazole plus (ceftriaxone or cefixime) plus (azithromycin or doxycycline) is the recommended empiric antimicrobial regimen for chlamydia, gonorrhea, and trichomonas.

Usual Adult Dose for Nongonococcal Urethritis

(Not approved by FDA)

CDC recommendations:
Recurrent or persistent urethritis: 2 g orally as a single dose

Comments:
-If the patient was compliant with the initial regimen and reexposure can be excluded, metronidazole plus azithromycin (if not used for initial episode) is recommended while waiting for results of diagnostic tests.

Usual Adult Dose for Balantidium coli

(Not approved by FDA)

Some experts recommend: 500 to 750 mg orally 3 times a day for 5 days

Comments:
-Recommended as an alternative agent.

Usual Adult Dose for Dientamoeba fragilis

(Not approved by FDA)

Some experts recommend: 500 to 750 mg orally 3 times a day for 10 days

Usual Pediatric Dose for Bacterial Infection

(Not approved by FDA)

American Academy of Pediatrics (AAP) General Dosing Recommendations for Susceptible Infections:
Neonates:
7 days or less, 2000 g or less: 7.5 mg/kg IV every 24 to 48 hours
7 days or less, greater than 2000 g: 15 mg/kg IV every 24 hours
8 to 28 days, 2000 g or less: 15 mg/kg IV every 24 hours
8 to 28 days, greater than 2000 g: 15 mg/kg IV every 12 hours

1 month or older:
IV: 22.5 to 40 mg/kg/day IV in 3 divided doses
Maximum dose: 1.5 g/day

Oral: 30 to 50 mg/kg/day orally in 3 divided doses
Maximum dose: 2.25 g/day

Comments:
-Therapy may start with a 15 mg/kg loading dose and the longer dosing interval may be used in extremely low birth weight (less than 1 kg) neonates.

Usual Pediatric Dose for Amebiasis

35 to 50 mg/kg/day orally in 3 divided doses for 10 days
Maximum dose: 750 mg/dose

Comments:
-Aspiration or drainage of pus is still needed for amebic liver abscess.
-Some experts (includes AAP) recommend this dose for mild to severe intestinal and extraintestinal disease; duration of therapy recommended is 7 to 10 days.

Approved indications: For the treatment of acute intestinal amebiasis (amebic dysentery) and amebic liver abscess

Usual Pediatric Dose for Pseudomembranous Colitis

(Not approved by FDA)

AAP recommendations:
Children and adolescents: 30 mg/kg/day orally in 4 divided doses
Maximum dose: 2 g/day
Duration of therapy: At least 10 days

Comments:
-Antimicrobial therapy for C difficile infection is recommended for symptomatic patients.
-Metronidazole is the drug of choice for initial treatment of mild to moderate diarrhea and for first relapse.
-Vancomycin enema plus IV metronidazole is recommended as initial therapy for patients with severe disease and for patients who do not respond to oral metronidazole.
-Metronidazole should not be used beyond the first recurrence or for chronic therapy due to possible neurotoxicity.

Usual Pediatric Dose for Trichomoniasis

(Not approved by FDA)

Some experts (includes AAP) recommend:
Children less than 45 kg with prepubertal vaginitis (sexually transmitted infection [STI]-related): 15 mg/kg/day orally in 3 divided doses for 7 days
Maximum dose: 2 g/day

Adolescent vulvovaginitis: 2 g orally as a single dose

Comments:
-If treatment failure occurs in adolescents and reinfection is excluded, 500 mg orally twice a day for 7 days is recommended.
-The patient's sexual partner(s) should be treated simultaneously with the same dose.

Usual Pediatric Dose for Bacterial Vaginosis

(Not approved by FDA)

Children less than 45 kg with prepubertal vaginitis (STI-related): 15 mg/kg/day orally in 2 divided doses for 7 days
Maximum dose: 1 g/day

Adolescent vulvovaginitis: 500 mg orally twice a day for 7 days

Comments:
-The patient's sexual partner(s) should also be evaluated/treated.

Usual Pediatric Dose for Giardiasis

(Not approved by FDA)

Some experts (includes AAP) recommend: 15 mg/kg/day orally in 3 divided doses for 5 to 7 days
Maximum dose: 250 mg/dose

Usual Pediatric Dose for STD Prophylaxis

(Not approved by FDA)

Prophylaxis after Sexual Assault:
AAP recommendations for preadolescent children:
Less than 45 kg: 15 mg/kg/day orally in 3 divided doses for 7 days
Maximum dose: 2 g/day

45 kg or more: 2 g orally as a single dose

Comments:
-Metronidazole plus ceftriaxone plus (azithromycin or erythromycin) is the recommended empiric antimicrobial regimen for patients less than 45 kg.
-Metronidazole plus (ceftriaxone or cefixime) plus (azithromycin or doxycycline [if at least 8 years of age]) is the recommended empiric antimicrobial regimen for patients at least 45 kg.

CDC recommendations for adolescents: 2 g orally as a single dose

Comments:
-Metronidazole plus (ceftriaxone or cefixime) plus (azithromycin or doxycycline) is the recommended empiric antimicrobial regimen for chlamydia, gonorrhea, and trichomonas.

Usual Pediatric Dose for Balantidium coli

(Not approved by FDA)

Some experts (includes AAP) recommend: 35 to 50 mg/kg/day orally in 3 divided doses for 5 days
Maximum dose: 750 mg/dose

Comments:
-Recommended as an alternative agent.

Usual Pediatric Dose for Dientamoeba fragilis

(Not approved by FDA)

Some experts (includes AAP) recommend: 35 to 50 mg/kg/day orally in 3 divided doses for 10 days
Maximum dose: 750 mg/dose

Renal Dose Adjustments

Data not available

Comments:
-Monitoring for drug-related side effects recommended.

Liver Dose Adjustments

Mild to moderate liver dysfunction: No adjustment recommended.

Severe liver dysfunction (Child-Pugh C):
Immediate-release tablet, capsule, and IV formulations: Dose should be reduced by 50%.

Indication specific adjustments for capsule formulation:
-Amebiasis: 375 mg orally every 8 hours for 5 to 10 days
-Trichomoniasis: 375 mg orally every 24 hours for 7 days

Extended-release tablet: Should not be used unless benefits considered to outweigh risks

Comments:
-Patients with liver dysfunction metabolize metronidazole slowly; metronidazole accumulates in the plasma.
-Monitoring for drug-related side effects recommended.

Precautions

Consult WARNINGS section for dosing related precautions.

Dialysis

Hemodialysis: If use of metronidazole cannot be separated from hemodialysis session, a supplemental dose of metronidazole after the session should be considered, depending on clinical situation of patient.

Comments:
-Significant amounts of metronidazole and its metabolites are removed from systemic circulation.
-Metronidazole clearance depends on type of dialysis membrane used, duration of dialysis session, and other factors.

Other Comments

Administration advice:
-IV metronidazole should be administered via slow IV drip infusion only, either as continuous or intermittent infusion.
-IV metronidazole cannot be given via direct IV injection (IV bolus) due to low pH (0.5 to 2) of the reconstituted product; it must be further diluted and neutralized for IV infusion.
-Equipment that contains aluminum and would come in contact with IV metronidazole solution (e.g., needles, cannulae) must not be used.
-IV therapy may be changed to oral metronidazole when conditions warrant, based upon severity of disease and response of patient.
-The extended-release formulation is only used for bacterial vaginosis; other indications use immediate-release formulations.

Storage requirements:
-Immediate-release tablet formulation should be stored below 25C (77F) and protected from light.
-Capsule formulation should be stored at controlled room temperature 15C to 25C (59F to 77F).
-Extended-release tablet formulation should be stored in a dry area at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).
-IV formulation should be stored below 25C (77F) and protected from light before reconstitution; reconstituted vials are stable for 96 hours when stored below 30C (86F) in room light; diluted and neutralized IV solutions should be used within 24 hours of mixing; neutralized solutions should not be refrigerated (precipitation may occur).

Reconstitution/preparation techniques:
-Order of mixing is important; first step is reconstitution; second step is dilution in IV solution followed by pH neutralization with sodium bicarbonate injection into the dilution.
-The manufacturer's product information should be consulted.

IV compatibility:
-IV admixtures containing metronidazole and other drugs should be avoided.
-Primary IV fluid should be stopped during metronidazole infusion.

Monitoring:
-General: For drug-related side effects in elderly patients and patients with renal and/or liver dysfunction
-Hematologic: Total and differential leukocyte counts (before and after therapy, especially if prolonged or repeated therapy)

Patient advice:
-Do not consume alcohol during therapy and for at least 72 hours after the last dose.

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