Metronidazole

Pronunciation: meh-troe-NID-uh-zole
Class: Anti-infective agent, GI agent, Vaginal preparation

Trade Names

Flagyl
- Tablets 250 mg
- Tablets 500 mg

Flagyl ER
- Tablets, extended-release 750 mg

Flagyl 375
- Capsules 375 mg

MetroCream
- Cream 0.75%

MetroGel
- Gel 0.75%
- Gel 1%

MetroGel-Vaginal
- Gel 0.75%

MetroLotion
- Lotion 0.75%

Metronidazole
- Injection, solution 5 mg/mL

Noritate
- Cream 1%

Vandazole
- Gel, vaginal 0.75%

Apo-Metronidazole (Canada)
Florazole ER (Canada)
Nida Gel (Canada)
Rosasol (Canada)

Pharmacology

Enters bacterial or protozoal cell and impairs synthesis of DNA, resulting in cell death.

Pharmacokinetics

Absorption

Oral metronidazole is well absorbed; topical application is less complete and more prolonged. Following administration, T max is 1 to 2 h, and C max is 25 mg/mL. Oral bioavailability is not affected by food, but peak serum levels will be delayed to 2 h. Following vaginal administration, C max and T max are 281 ng/mL and 9.5 h, respectively.

Distribution

Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations similar to those found in plasma. Less than 20% is protein bound.

Metabolism

Metabolites are 2–hydroxymethyl and acidic metabolite.

Elimination

Routes of elimination are via urine (60% to 80%) and feces (6% to 15%). Renal Cl is approximately 10 mL/min per 1.73 m 2 . The half-life is 8 h in healthy adults, and the hydroxy-metabolite half-life is 15 h.

Special Populations

Renal Function Impairment

Decreased renal function does not alter single-dose pharmacokinetics of metronidazole.

Hepatic Function Impairment

Patients with hepatic impairment metabolized metronidazole slower; accumulation of drug may occur. Cautiously administer doses below the usual recommended dose.

Elderly

Because the pharmacokinetics of metronidazole may be altered in elderly patients, monitoring of serum levels may be necessary to adjust the dosage accordingly.

Indications and Usage

Treatment of serious infections caused by susceptible anaerobic bacteria; prophylaxis of postoperative infection in patients undergoing colorectal surgery; treatment of amebiasis; treatment of trichomoniasis and asymptomatic partners of infected patients; bacterial vaginosis ( Flagyl ER only).

Topical

Treatment of inflammatory papules, pustules, and erythema of acne rosacea.

Vaginal

Treatment of bacterial vaginosis.

Unlabeled Uses

Treatment of hepatic encephalopathy, Crohn disease, antibiotic-associated pseudomembranous colitis, Helicobacter pylori infections.

Contraindications

Hypersensitivity to nitroimidazole derivatives or any component of the products; first trimester of pregnancy in patients with trichomoniasis.

Dosage and Administration

Amebiasis
Adults

PO

Flagyl 375 capsules

Acute amebic dysentery and amebic liver abscess: 750 mg 3 time daily for 5 to 10 days.

Flagyl 250 mg tablets

Acute amebic dysentery: 750 mg 3 times daily for 5 to 10 days. Amebic liver abscess: 500 or 750 mg 3 times daily for 5 to 10 days.

Children

PO

Flagyl 375 , Flagyl 250 mg tablets

35 to 50 mg/kg per 24 h divided into 3 daily doses for 10 days.

Anaerobic Bacterial Infections

Give IV initially when treating most serious anaerobic infections.

Adults

IV 15 mg/kg loading dose infused over 1 h (approximately 1 g for a 70 kg adult); then a maintenance dose of 7.5 mg/kg infused over 1 h every 6 h (approximately 500 mg for a 70 kg adult). The first maintenance dose should be given 6 h following initiation of loading dose. Do not exceed 4 g in 24 h. May follow with similar oral dose. For prophylaxis, loading dose is to be completed 1 h before surgery, followed by maintenance dose 6 and 12 h later.

Duration

The usual duration is 7 to 10 days; however, infections of the bone, joint, lower respiratory tract, and endocardium may require longer treatment.

Adults

PO

Flagyl 375 , Flagyl 250 mg tablets

Usual dosage is 7.5 mg/kg (approximately 500 mg for a 70 kg adult) every 6 h (max, 4 g per 24 h) for 7 to 10 days; however, infections of the bone, joint, lower respiratory tract, and endocardium may require longer treatment.

Bacterial Vaginosis
Adults

PO 750 mg ( Flagyl ER ) daily for 7 consecutive days. Vaginal 1 applicator-full (approximately 37.5 mg metronidazole) intravaginally once or twice daily for 5 days; for daily dosing, administer at bedtime

Hepatic Function Impairment

PO/IV Use lower doses cautiously and close monitoring of plasma metronidazole levels and toxicity is recommended.

Inflammatory Papules and Pustules of Rosacea
Adults

Topical Apply thin layer once daily (1% cream) or twice daily to entire affected areas after washing. Use morning and evening or as directed by health care provider. Avoid application close to eyes.

Trichomoniasis

Individualize treatment for women and men.

Adults

PO

Flagyl 375 capsules

Women: 375 mg twice daily for 7 consecutive days. When a repeat course is required, a lapse of 4 to 6 wk between courses is recommended.

Flagyl 250 mg tablets

250 mg 3 times daily for 7 consecutive days.

One-day treatment

2 g as a single dose or in 2 divided doses of 1 g each given on the same day.

Children

PO 5 mg/kg/dose 3 times daily for 7 days.

General Advice

  • Injection
  • Administer by slow IV drip infusion only, either as continuous or intermittent infusion. Not for intradermal, subcutaneous, or IM administration.
  • Solution is administered directly from original IV container. No further dilution is required.
  • Do not administer using equipment containing aluminum (eg, needles, cannulae) that may come in or make contact with drug solution.
  • Administer prescribed dose over 30 to 60 min.
  • Do not administer if particulate matter, cloudiness, or discoloration are noted or if the seals are not intact.
  • Do not add other drugs to the metronidazole infusion bag.
  • If other drugs are being administered through the same IV line, flush it before and after infusion of metronidazole. If being used with a primary IV fluid system, discontinue the primary solution during metronidazole infusion.
  • Do not use plastic containers in series connections.

Storage/Stability

Store extended-release tablets, vaginal gel, topical cream, injection, and topical gel at 59° to 86°F. Protect from freezing. Store tablets, capsules, topical lotion, and injection below 77°F. Protect injection from light until use and avoid excessive heat.

Drug Interactions

Anticoagulants (eg, warfarin)

Anticoagulant effect may be increased.

Barbiturates, phenytoin

Therapeutic failure of metronidazole may occur.

Cimetidine

May prolong the half-life and decrease plasma Cl of metronidazole.

Disulfiram

Concurrent use may result in acute psychosis or confusional state. Do not give metronidazole to patients who have taken disulfiram within last 2 wk.

Ethanol

Disulfiram-like reaction including flushing, palpitations, tachycardia, nausea, and vomiting may occur with concurrent use.

Lithium

Plasma levels may be elevated by metronidazole, increasing the risk of lithium toxicity.

Incompatibility

Do not use aluminum-containing equipment with metronidazole because solution will turn orange/rust color.

Laboratory Test Interactions

May interfere with chemical analyses for AST, ALT, LDH, triglycerides, and hexokinase glucose; zero values may occur.

Adverse Reactions

CNS

Headache (18%); dizziness (4%); seizures; optic and peripheral neuropathy; vertigo; incoordination; ataxia; confusion; depression; insomnia; syncope; irritability; weakness; encephalopathy; aseptic meningitis; dysarthria.

Dermatologic

Pruritis (6%); generalized itching or rash, skin irritation, transient skin erythema, mild skin dryness and burning (2%); thrombophlebitis after IV use; urticaria; erythematous rash; flushing; local allergic reaction, contact dermatitis, worsening of rosacea, transient redness; Steven-Johnson syndrome.

EENT

Metallic taste (9%); rhinitis (4%); sinusitis, pharyngitis (3%); nasal congestion.

GI

Nausea (10%); GI discomfort (7%); abdominal pain (5%); diarrhea, vomiting (4%); unusual taste (2%); decreased appetite (1%). anorexia; constipation; epigastric distress; cramps; pseudomembranous colitis; furry tongue; glossitis; stomatitis; pancreatitis.

Genitourinary

Vaginitis (15%); vaginal discharge (12%); symptomatic Candida cervicitis/vaginitis (10%); vulva/vaginal irritative symptoms (9%); genital pruritus (5%); abnormal urine, dysmenorrhea, pelvic discomfort (3%); UTI (2%); breast pain, metrorrhagia (1%); darkening of urine; dysuria; cystitis; polyuria; incontinence; decreased libido; proctitis; dyspareunia.

Hematologic

Mild leukopenia; reversible thrombocytopenia; reversible neutropenia.

Miscellaneous

Fungal infection (12%); bacterial infection (7%); influenza-like symptoms (6%); upper respiratory tract infection (4%); moniliasis (3%); infection, unspecified cramping (1%); hypersensitivity reactions including dermatologic reactions, dry mouth or vagina, and fever; fleeting joint pain; flattening of T-wave.

Precautions

Warnings

Oral and IV metronidazole have been carcinogenic in mice and rats. Avoid unnecessary use.


Monitor

Monitor total and differential leukocyte counts before and after IV therapy. Monitor patient for neurological adverse reactions.


Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established, except for amebiasis (tablets/capsules only). The safety and efficacy of vaginal metronidazole has not been established in premenarchal females.

Elderly

Monitoring serum levels may be necessary for proper dosing.

Hepatic Function

Patients with severe hepatic disease metabolize drug slowly; use caution and lower dose.

Special Risk Patients

Use with caution in patients predisposed to edema or patients receiving corticosteroids.

Candidiasis

Known or previously unrecognized candidiasis may present more prominent symptoms during therapy.

Hematologic effects

Use with caution in patients with a history of blood dyscrasia.

Neurologic effects

Seizures and peripheral neuropathy have occurred. Use extra caution with prolonged use, high doses, or history of CNS disease.

Overdosage

Symptoms

Nausea, vomiting, ataxia, seizures, peripheral neuropathy.

Patient Information

  • Instruct patient to take exactly as prescribed and not to change dose or discontinue therapy unless advised by health care provider.
  • Instruct patient to notify health care provider if infection does not appear to be improving or appears to be getting worse.
  • Caution patient to avoid alcoholic beverages while taking metronidazole and for at least 1 day (tablets) or 3 days (capsules and extended-release tablets) following completion of therapy.
  • Advise patient that metallic taste is a common adverse reaction of therapy but that this will resolve when therapy has been discontinued.
  • Advise patient to report any other bothersome adverse reactions to health care provider and to immediately report any abnormal neurologic signs or symptoms (eg, seizures, extremity numbness, abnormal skin sensations).
  • Tablets and capsules
  • Advise patient to take prescribed dose without regard to meals but to take with food if GI upset occurs.
  • Extended-release tablets
  • Advise patient to take prescribed dose daily, 1 h before or 2 h after a meal.
  • Caution patient to swallow extended-release tablet whole and not crush, chew, or divide.
  • Vaginal gel
  • Review instructions for filling applicator, administering medication, and care of applicator.
  • Advise patient that if accidental contact of the gel with the eye(s) occurs, to rinse the eye(s) with copious amounts of cool tap water. Advise patient to notify health care provider if eye irritation persists after rinsing.
  • Advise patient to avoid vaginal intercourse or use of other vaginal products (eg, tampons) during treatment.
  • Advise patient to discontinue use and notify health care provider if vaginal irritation develops while using the medication.
  • Topical
  • Advise patient to cleanse areas to be treated before applying medication, then apply and rub in a thin film twice daily to entire affected areas.
  • Advise patient that cosmetics may be applied after application of medication but if using lotion, to allow it to dry first.
  • Advise patient that if local irritation occurs to apply the medication less frequently. If irritation persists, advise patient to discontinue use and notify health care provider.
  • Injection
  • Advise patient, family, or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
  • Advise patient to report injection-site pain or redness.

Copyright © 2009 Wolters Kluwer Health.

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