Metronidazole

Indications

Oral
Amoebiasis
Adult: 400-800 mg tid for 5-10 days or 1.5-2.5 g as a single daily dose for 2-3 days. Alternatively, 1.5-2.5 g as a single dose for 2-3 days.
Child: 1-3 yr: ¼ adult dose; 3-7 yr: ¹/₃ adult dose; 7-10 yr: ½ adult dose. Alternatively, 35-50 mg/kg daily in divided doses.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Balantidiasis
Adult: 400-800 mg tid for 5-10 days or 1.5-2.5 g as a single daily dose for 2-3 days. Alternatively, 1.5-2.5 g as a single dose for 2-3 days.
Child: 1-3 yr: ¼ adult dose; 3-7 yr: ¹/₃ adult dose; 7-10 yr: ½ adult dose. Alternatively, 35-50 mg/kg daily in divided doses.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Blastocystis hominis infection
Adult: 400-800 mg tid for 5-10 days or 1.5-2.5 g as a single daily dose for 2-3 days. Alternatively, 1.5-2.5 g as a single dose for 2-3 days.
Child: 1-3 yr: ¼ adult dose; 3-7 yr: ¹/₃ adult dose; 7-10 yr: ½ adult dose. Alternatively, 35-50 mg/kg daily in divided doses.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Trichomoniasis
Adult: 2 g as a single dose, or 800 mg in the morning and 1.2 g in the evening for 2 days, or 0.6-1 g daily in 2-3 divided doses for 7 days. There should be an interval of 4-6 wk if treatment needs to be repeated.
Child: 1-3 yr: 50 mg tid; 3-7 yr: 100 mg bid; 7-10 yr: 100 mg tid. All doses to be taken for 7 days. Alternatively, 15 mg/kg daily in divided doses for 7 days.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Giardiasis
Adult: 2 g once daily for 3 consecutive days, or 400 mg tid for 5 days, or 500 mg bid for 7-10 days.
Child: 1-3 yr: ¼ adult dose; 3-7 yr: ¹/₃ adult dose; 7-10 yr: ½ adult dose. Alternatively, 15 mg/kg daily in divided doses.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Bacterial vaginosis
Adult: 2 g as a single dose, or 400-500 mg bid for 5-7 days.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Acute necrotising ulcerative gingivitis
Adult: 200 mg tid for 3 days.
Elderly: Dose reductions may be required.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Acute dental infections
Adult: 200 mg tid for 3 days.
Elderly: Dose reductions may be required.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Anaerobic bacterial infections
Adult: Initially, 800 mg followed by 400 mg 8 hly for about 7 days. Other recommended doses: 500 mg 8 hrly or 7.5 mg/kg 6 hrly (max: 4 g in 24 hr).
Child: 7.5 mg/kg 8 hrly.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Prophylaxis of postoperative anaerobic bacterial infections
Adult: 400 mg by mouth 8 hrly in the 24 hr prior to surgery followed postoperatively by IV or rectal admin until oral therapy is possible. Other sources recommend that oral doses be initiated only 2 hr prior to surgery and that number of doses for all admin routes be limited to a total of 4.
Elderly: Dose reduction may be necessary.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Eradication of H. pylori associated with peptic ulcer disease
Adult: In combination with another antibacterial (e.g. clarithromycin) plus either a proton pump inhibitor (e.g. lansoprazole) or ranitidine bismuth citrate: 400 mg bid. In combination with omeprazole and amoxicillin: 400 mg tid. Continue treatment for 1 wk.
Elderly: Dose reduction may be necessary.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Leg ulcers and pressure sores
Adult: 400 mg tid for 7 days.
Elderly: Dose reduction may be necessary.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Oral
Antibiotic-associated colitis
Adult: 250-500 mg bid-tid for 10-14 days. Transfer to oral vancomycin is recommended if there is no clear clinical response after 2 days of treatment.
Child: 20 mg/kg/day 6 hrly. Max dose: 2 g/day. Transfer to oral vancomycin is recommended if there is no clear clinical response after 2 days of treatment.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Intravenous
Anaerobic bacterial infections
Adult: 500 mg infused as 100 ml of a 5 mg/ml solution at 5 ml/min 8 hrly. Alternatively, 15 mg/kg infusion followed by 7.5 mg/kg 6 hrly; infuse over 1 hr (max: 4 g in 24 hr). Substitute oral therapy as soon as possible.
Child: 7.5 mg/kg 8 hrly.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Intravenous
Prophylaxis of postoperative anaerobic bacterial infections
Adult: 500 mg by IV infusion shortly before operation and repeated 8 hrly; oral doses of 200 or 400 mg 8 hrly being substituted as soon as possible. Patient undergoing colorectal surgery: 15 mg/kg infused over 30-60 min, completed about 1 hr prior to surgery, followed by 2 further IV doses of 7.5 mg/kg infused at 6 and 12 hr after the initial dose.
Elderly: Use lower end of adult dose recommendations. Do not admin as a single dose.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Topical/Cutaneous
Bacterial vaginosis
Adult: Apply 5 g of a 0.75% gel once or bid for 5 days.
Rectal
Anaerobic infections
Adult: As a 1-g suppository 8 hrly for 3 days, then 12 hrly. Substitute oral therapy as soon as possible. May be unsuitable for initiating therapy in severe infections.
Child: <1 yr: 125 mg; 1-5 yr: 250 mg; 5-10 yr: 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter. May be unsuitable for initiating therapy in severe infections.
Elderly: Dose reduction may be necessary.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Hepatic impairment: Severe: ¹/₃ of usual dose given once daily.
Rectal
Prophylaxis of postoperative anaerobic bacterial infections
Adult: 1 g 8 hrly starting 2 hr before surgery.
Elderly: Dose reduction may be necessary.

CrCl (ml/min)	Dosage Recommendation
<10	Consider reducing dose during long-term therapy.

Topical/Cutaneous
Fungating tumours
Adult: Apply as a 0.75 or 0.8% gel to the affected area.
Topical/Cutaneous
Rosacea
Adult: Apply and rub a thin film once daily (1% formulation) or bid (0.75% formulation) to entire affected areas after washing. Significant response should be noticed within 3 wk. Clinical studies have demonstrated continuing improvement through 9 wk of therapy.

Special Populations: Reduce dose in patients with severe hepatic impairment.

Reconstitution: Reconstitute powder for inj by adding 4.4 ml of sterile or bacteriostatic water for inj, 0.9% sodium chloride inj or bacteriostatic sodium chloride inj to a vial labeled as containing 500 mg metronidazole. Reconstituted solution contains approx 100 mg/ml metronidazole and must be further diluted with 0.9% sodium chloride inj, 5% dextrose inj or lactated Ringer's inj to a concentration of ≤8 mg/ml metronidazole. Neutralise reconstituted and diluted metronidazole hydrochloride solution by adding approx 5 mEq of sodium bicarbonate inj for each 500 mg metronidazole.
Incompatibility: Incompatible with aztreonam, dopamine, meropenem.

Contraindications

History of hypersensitivity to metronidazole or other nitroimidazole derivatives. Pregnancy (1st trimester) and lactation.

Warnings / Precautions

Patients with CNS diseases; discontinue IV therapy if abnormal neurologic symptoms occur. History of seizure disorder. Evidence or a history of blood dyscrasias; perform total and differential leukocyte counts before and after treatment. Severe hepatic impairment; monitor plasma levels. Predisposition to oedema (inj contains sodium). Prolonged use may result in fungal or bacterial superinfection.

Adverse Reactions

GI disturbances e.g. nausea, unpleasant metallic taste, vomiting, diarrhoea or constipation. Furred tongue, glossitis, and stomatitis due to overgrowth of Candida. Rarely, antibiotic-associated colitis. Weakness, dizziness, ataxia, headache, drowsiness, insomnia, changes in mood or mental state. Numbness or tingling in the extremities, epileptiform seizures (high doses or prolonged treatment). Transient leucopenia and thrombocytopenia. Hypersensitivity reactions. Urethral discomfort and darkening of urine. Raised liver enzyme values, cholestatic hepatitis, jaundice. Thrombophlebitis (IV).
Potentially Fatal: Anaphylaxis.

Overdose Reactions

Symptoms: Nausea, vomiting, ataxia, seizures, peripheral neuropathy. Management: Symptomatic and supportive.

Drug Interactions

Acute psychoses or confusion with disulfiram. Additive/synergistic effect with other antimicrobials. Effects reduced with phenobarbital or phenytoin.
Potentially Fatal: Disulfiram-like reaction with alcohol. Increased risk of adverse effects of coumarin anticoagulants, phenytoin, lithium, ciclosporin, fluorouracil. Increased risk of neurological effects with cimetidine.
See Below for More metronidazole Drug Interactions

Lab Interactions

May interfere with tests for aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, glucose and lactate dehydrogenase (LDH).

Mechanism of Actions

Metronidazole is converted to reduction products that interact with DNA to cause destruction of helical DNA structure and strand leading to a protein synthesis inhibition and cell death in susceptible organisms. It is effective against a wide range of organisms including E. histolytica, T. vaginalis, Giardia, anaerobes e.g. Bacterioides sp, Fusobacterium sp, Clostridium sp, Peptococcus sp and Peptostreptococcus sp, and moderately active against Gardnerella sp and Campylobacter sp.
Absorption: Readily absorbed from the GI tract (oral), poorly absorbed from the vagina (intravaginal); peak plasma concentrations after 1-2 hr (oral), 5-12 hr (rectal), 8 hr (intravaginal). May be delayed by the presence of food.
Distribution: Protein-binding: <20%. Widely distributed in body tissues and fluids e.g. bile, bone, breast milk, cerebral abscesses, CSF, liver and liver abscesses, saliva, semenal fluid, vaginal secretions (concentrations similar to those in plasma); crosses the placenta and rapidly enters fetal circulation.
Metabolism: Hepatic via side-chain oxidation and glucuronide formation.
Excretion: Mainly via urine (as metabolites); via faeces (small amounts). Elimination half-life: 8 hr; longer in neonates and severe hepatic impairment.

Administration

Tab: Should be taken with food.
Susp: Should be taken on an empty stomach. (Take at least 1 hr before meals.)

Storage Conditions

Intravenous: Store at 15-30°C and protect from light.

ATC Classification

D06BX01 - metronidazole ; Belongs to the class of other topical chemotherapeutics used in the treatment of dermatological diseases.
G01AF01 - metronidazole ; Belongs to the class of imidazole derivative antiinfectives. Used in the treatment of gynecological infections.
A01AB17 - metronidazole ; Belongs to the class of local antiinfective and antiseptic preparations. Used in the treatment of diseases of the mouth.
J01XD01 - metronidazole ; Belongs to the class of imidazole derivative antibacterials. Used in the systemic treatment of infections.
P01AB01 - metronidazole ; Belongs to the class of nitroimidazole derivatives antiprotozoals. Used in the treatment amoebiasis and other protozoal diseases.