metronidazole
Apo-Metronidazole ◆, Flagyl, Flagyl ER, Metric 21, Novonidazol ◆, Protostat

metronidazole hydrochloride
Flagyl IV, Flagyl IV RTU, Metro I.V.

Available forms
Available by prescription only
Capsules: 375 mg
Injection: 500 mg/dl ready to use
Powder for injection: 500-mg single-dose vials
Tablets: 250 mg, 500 mg
Tablet (extended-release, film-coated): 750 mg
Tablets (film-coated): 250 mg, 500 mg

Indications and dosages
 Amebic hepatic abscess. Adults: 500 to 750 mg P.O. t.i.d. for 5 to 10 days. Or, 2.4 g P.O. daily for 1 to 2 days or 500 mg I.V. q 6 hours for 10 days. Children: 30 to 50 mg/kg P.O. daily (in three doses) for 5 to 10 days. Or, 1.3 g/m² P.O. daily in three divided doses for 5 to 10 days.
 Intestinal amebiasis. Adults: 750 mg P.O. t.i.d. for 5 to 10 days. Centers for Disease Control and Prevention recommends addition of iodoquinol 650 mg P.O. t.i.d. for 20 days. Or, 2.4 g P.O. daily for 1 to 2 days or 500 mg I.V. q 6 hours for 10 days.
Children ◇: 30 to 50 mg/kg P.O. daily (in three divided doses) for 5 to 10 days. Follow this therapy with oral iodoquinol. Or, 1.3 g/m² P.O. daily in three divided doses for 5 to 10 days.
 Trichomoniasis. Adults: 375-mg capsule P.O. b.i.d. for 7 days, or 500-mg tablet P.O. b.i.d. for 7 days, or a single dose of 2 g P.O. or divided into two doses given on same day.
Children ◇: 15 mg/kg P.O. daily (in three divided doses) for 7 to 10 days. Or, 40 mg/kg P.O. as a single dose. Dose shouldn’t exceed 2 g.
Infants older than age 4 weeks ◇: 10 to 30 mg/kg P.O. daily for 5 to 8 days.
 Refractory trichomoniasis. Adult women: 500 mg P.O. b.i.d. for 7 days. If repeated failure, 2 g P.O. daily for 3 to 5 days. Or (for repeated failure), 2 to 3.5 g P.O. daily for 3 to 21 days depending on in vitro susceptibility testing.
 Bacterial infections caused by anaerobic microorganisms. Adults: Loading dose is 15 mg/kg I.V. infused over 1 hour (about 1 g for a 70-kg [154-lb] adult). Maintenance dosage is 7.5 mg/kg I.V. or P.O. q 6 hours (about 500 mg for a 70-kg adult). Administer first maintenance dose 6 hours after the loading dose. Maximum dose shouldn’t exceed 4 g daily. Continue therapy for 7 days to 3 weeks.
 Giardiasis ◇. Adults: 250 mg P.O. t.i.d. for 5 days, or 2 g once daily for 3 days. If coexistent amebiasis, 750 mg P.O. t.i.d. for 5 to 10 days.
Children: 5 mg/kg P.O. t.i.d. for 5 to 7 days.
 Prevention of postoperative infection in contaminated or potentially contaminated colorectal surgery. Adults: 15 mg/kg infused over 30 to 60 minutes and completed about 1 hour before surgery. Then 7.5 mg/kg infused over 30 to 60 minutes at 6 and 12 hours after initial dose. If used with oral neomycin or oral kanamycin, 750 mg P.O. b.i.d. to t.i.d. beginning 2 days before surgery. Or, 500 mg to 1 g I.V. 1 hour before surgery followed by 500 mg I.V. at 8 and 16 hours postoperatively.
 Bacterial vaginosis ◇. Adults: 500 mg P.O. b.i.d. for 7 days. Or, 2 g P.O. as a single dose. Or, 750 mg (extended-release) P.O. daily for 7 days. If during pregnancy, 250 mg P.O. t.i.d. for 7 days or 2 g P.O. as a single dose.
 Pelvic inflammatory disease. Adults: 500 mg I.V. q 12 hours with I.V. ofloxacin or I.V. ciprofloxacin and I.V. or oral doxycycline.
 Pelvic inflammatory disease (ambulatory patients) ◇. Adults: 500 mg P.O. b.i.d. for 14 days (given with 400 mg b.i.d. of ofloxacin).
 Infection with Clostridium difficile ◇. Adults: 750 mg to 2 g P.O. daily, in three to four divided doses for 7 to 14 days. Or, 500 to 750 mg I.V. q 6 to 8 hours when oral dosing isn’t feasible.
 Helicobacter pylori related to peptic ulcer disease ◇. Adults: 250 to 500 mg P.O. t.i.d. to q.i.d. (with other drugs). Continue for 7 to 14 days depending on regimen used.
Children: 15 to 20 mg/kg P.O. daily, divided in two doses for 4 weeks (with other drugs).
 Amebiasis caused by Dientamoeba fragilis ◇. Children: 250 mg P.O. t.i.d. for 7 days.
 Entamoeba polecki infection ◇. Adults: 750 mg P.O. t.i.d. for 10 days.
Children: 35 to 50 mg/kg P.O. daily in three divided doses for 10 days.
 Dracunculiasis caused by Dracunculus medinensis (guinea worm infection) ◇. Adults: 250 mg P.O. t.i.d. for 10 days.
Children: 25 mg/kg daily P.O. in three divided doses (up to 750 mg daily) for 10 days.
 Balantidiasis caused by Balantidium coli ◇. Adults: 750 mg P.O. t.i.d. for 5 days.
Children: 35 to 50 mg/kg P.O. daily in three divided doses for 5 days.
 Symptomatic Blastocystis hominis infection ◇. Adults: 750 mg P.O. t.i.d. for 10 days.
 Active Crohn’s disease ◇. Adults: 400 mg P.O. b.i.d. For refractory perineal disease, 20 mg/kg (1 to 1.5 g) in three to five divided doses daily.
 Prophylaxis in sexual assault victims ◇. Adults: 2 g P.O. with other drugs.

Pharmacodynamics
Bactericidal, amebicidal, and trichomonacidal actions: The nitro group of metronidazole is reduced inside the infecting organism; this reduction product disrupts DNA and inhibits nucleic acid synthesis, causing cell death. Drug is active in intestinal and extraintestinal sites. It’s active against most anaerobic bacteria and protozoa, including Bacteroides fragilis, B. melaninogenicus, Fusobacterium, Veillonella, Clostridium, Peptococcus, Peptostreptococcus, Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia, and B. coli.

Pharmacokinetics
Absorption: About 80% of an oral dose is absorbed; food delays the rate but not the extent of absorption.
Distribution: Distributed into most body tissues and fluids, including CSF, bone, bile, saliva, pleural and peritoneal fluids, vaginal secretions, seminal fluids, middle ear fluid, and hepatic and cerebral abscesses. CSF levels approach serum levels in patients with inflamed meninges; they reach about 50% of serum levels in patients with uninflamed meninges. Less than 20% of metronidazole is bound to plasma proteins. It readily crosses the placental barrier.
Metabolism: Metabolized to an active 2-hydroxymethyl metabolite and also to other metabolites.
Excretion: About 60% to 80% of dose is excreted as parent compound or its metabolites. About 20% of a metronidazole dose is excreted unchanged in urine; about 6% to 15% is excreted in feces. Half-life of drug is 6 to 8 hours in adults with normal renal function; its half-life may be prolonged in patients with impaired hepatic function.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other nitroimidazole derivatives. Use cautiously in patients with Crohn’s disease, history of blood dyscrasia or alcoholism, hepatic disease, retinal or visual field changes, or CNS disorders and in those receiving hepatotoxic drugs.

Interactions
Drug-drug. Barbiturates, phenytoin: Reduces antimicrobial effectiveness of metronidazole. Patient may need higher metronidazole dosage.
Disulfiram: May precipitate psychosis and confusion. Avoid use together.
Lithium: May increase lithium levels. Monitor serum lithium levels.
Oral anticoagulants: Prolongs PT and INR. Monitor patient for increased bruising or bleeding.
Drug-lifestyle. Alcohol use: May cause disulfiram-like reaction (nausea, vomiting, headache, abdominal cramps, and flushing). Discourage alcohol use.

Adverse reactions
CNS: vertigo, headache, ataxia, dizziness, syncope, uncoordination, confusion, irritability, fever, depression, weakness, insomnia, seizures, peripheral neuropathy.
CV: ECG change (flattened T wave), edema (with I.V. ready-to-use preparation), flushing.
GI: abdominal cramping, stomatitis, metallic taste, epigastric distress, nausea, vomiting, anorexia, diarrhea, constipation, proctitis, dry mouth.
GU: darkened urine, polyuria, dysuria, cystitis, dyspareunia, dryness of vagina and vulva, vaginal candidiasis.
Hematologic: transient leukopenia, neutropenia, thrombocytopenia.
Musculoskeletal: fleeting joint pain.
Skin: rash.
Other: overgrowth of nonsusceptible organisms, especially Candida (glossitis, furry tongue); thrombophlebitis (after I.V. infusion); decreased libido.

Effects on lab test results
• May decrease WBC, platelet, and neutrophil counts.

Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, ataxia, seizures, and peripheral neuropathy.
 There’s no known antidote for metronidazole; treatment is supportive. If patient doesn’t vomit spontaneously, induced emesis or gastric lavage is indicated for an oral overdose; activated charcoal and a cathartic may be used. Diazepam or phenytoin may be used to control seizures.

Special considerations
• Injection contains 28 mEq of sodium per gram of metronidazole.
• Trichomoniasis should be confirmed by wet smear and amebiasis by culture before giving metronidazole.
• When preparing powder for injection, follow manufacturer’s instructions carefully; use solution prepared from powder within 24 hours. I.V. solutions must be prepared in three steps: reconstitution with 4.4 ml of normal saline solution injection (with or without bacteriostatic water); dilution with lactated Ringer’s injection, D₅W, or normal saline solution; and neutralization with sodium bicarbonate, 5 mEq per 500 mg metronidazole. Final concentration should be 8 mg/ml or less.
• Don’t refrigerate neutralized solution to avoid precipitation.
• Administer I.V. form by slow infusion only; if used with a primary I.V. fluid system, discontinue the primary fluid during the infusion; don’t give by I.V. push.
 ALERT Infuse drug over 30 minutes to 1 hour. Don’t give I.V. push.
• Drug may interfere with the chemical analyses of aminotransferases and triglyceride, leading to falsely decreased values.
• Monitor patient for candidiasis during I.V. therapy.
• When treating amebiasis, monitor number and character of stools. Send fecal specimens to the laboratory promptly; infestation is detectable only in warm specimens. Repeat fecal studies at 3-month intervals to ensure elimination of organisms.
Pregnant patients
• If indicated during pregnancy for trichomoniasis, the 7-day regimen is preferred over the single-dose regimen. Avoid treatment with metronidazole during the first trimester.
Breast-feeding patients
• Patient should discontinue breast-feeding while taking drug.
Pediatric patients
• Neonates may eliminate drug more slowly than older infants and children.

Patient education
• Inform patient that drug may cause metallic taste and discolored (red-brown) urine.
• Tell patient to take tablets with meals to minimize GI distress and that tablets may be crushed to facilitate swallowing.
• Counsel patient on need for medical follow-up after discharge. Explain importance of completing full course of therapy.
• Advise patient to report adverse effects.
• Tell patient to avoid alcohol and alcohol-containing drugs during therapy and for at least 48 hours after the last dose to prevent disulfiram-like reaction.
• Tell patient to take extended-release form on empty stomach.
• Explain to patient with amebiasis that follow-up examinations of stool specimens are needed for 3 months after treatment is discontinued, to ensure elimination of amebae.
• To help prevent reinfection of amebiasis, instruct patient and family members in proper hygiene, including disposal of feces and washing of hands after defecation and before handling, preparing, or eating food. Explain the risks of eating raw food and the need to control contamination by flies.
• Encourage other household members and suspected contacts to be tested for amebiasis and, if necessary, treated.
• For patient with trichomoniasis, teach correct personal hygiene, including perineal care.
• Explain that asymptomatic sexual partners of patients being treated for trichomoniasis should be treated simultaneously to prevent reinfection; patient should refrain from intercourse during therapy or have partner use condom.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use