metronidazole

REMS

PO: IV: Treatment of the following anaerobic infections:
- Intra-abdominal infections (may be used with a cephalosporin),
- Gynecologic infections,
- Skin and skin structure infections,
- Lower respiratory tract infections,
- Bone and joint infections,
- CNS infections,
- Septicemia,
- Endocarditis.
IV: Perioperative prophylactic agent in colorectal surgery.
PO: Treatment of the following infections:
- Amebic dysentery, amebic liver abscess, and trichomoniasis.
- Peptic ulcer disease caused by
  Helicobacter pylori
  .
Acne rosacea.
Bacterial vaginosis.

Unlabeled Use:

Giardiasis.
Anti-infective associated
Clostridioides difficile
-associated diarrhea (CDAD).

Action ⬆ ⬇

Disrupts DNA and protein synthesis in susceptible organisms.

Therapeutic effects:

Bactericidal, trichomonacidal, or amebicidal action.

Spectrum:

Most notable for activity against anaerobic bacteria, including:
- Bacteroides spp.,
- Clostridioides difficile,
- Gardnerella vaginalis,
- Mobiluncus spp.,
- Peptostreptococcus spp.
In addition, is active against:
- Trichomonas vaginalis,
- Entamoeba histolytica,
- Giardia lamblia,
- H. pylori.

Pharmacokinetics ⬆ ⬇

Absorption: 80% absorbed after oral administration. Minimal absorption after topical or vaginal application.

Distribution: Widely distributed into most tissues and fluids, including CSF.

Metabolism/Excretion: Partially metabolized by the liver (30–60%), partially excreted unchanged in the urine, 6–15% eliminated in the feces.

Half-Life: Neonates: 25–75 hr; Children and adults: 6–12 hr.

Time/Action Profile ⬆ ⬇

(PO, IV = plasma concentrations; topical = improvement in rosacea)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1–3 hr	8 hr
PO-ER	rapid	unknown	up to 24 hr
IV	rapid	end of infusion	6–8 hr
Topical	3 wk	9 wk	12 hr
Vaginal	unknown	6–12 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypersensitivity to parabens (topical only);
Cockayne syndrome (↑ risk of hepatotoxicity and death);
OB: First trimester of pregnancy.

Use Cautiously in:

History of blood dyscrasias;
History of seizures or neurologic problems;
Severe hepatic impairment (dose ↓ suggested);
Patients receiving corticosteroids or predisposed to edema (injection contains 28 mEq sodium/g metronidazole);
OB: Although safety has not been established, has been used to treat trichomoniasis in 2nd- and 3rd-trimester pregnancy, but not as single-dose regimen;
Lactation: If needed, use single dose and interrupt nursing for 24 hr thereafter.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria,

topical only

burning, mild dryness, skin irritation, transient redness

EENT: hearing impairment, optic neuropathy, tearing (topical only)

GI: abdominal pain, anorexia, nausea, diarrhea, dry mouth, furry tongue, glossitis, unpleasant taste, vomiting

Hemat: leukopenia

Local: phlebitis at IV site

Neuro: dizziness, headache, aseptic meningitis (IV), encephalopathy (IV), peripheral neuropathy, psychosis, SEIZURES

Misc: superinfection

Interactions ⬆ ⬇

Drug-drug:

Cimetidine may ↑ levels and risk of toxicity.
Phenobarbital and rifampin may ↓ levels and effectiveness.
May ↑ levels and the risk of toxicity of phenytoin, lithium, and warfarin.
Disulfiram-like reaction may occur with alcohol ingestion.
May cause acute psychosis and confusion with disulfiram.
↑risk of leukopenia with fluorouracil or azathioprine.
Use with QT interval prolonging medications may ↑ risk of QT interval prolongation.

Route/Dosage ⬆ ⬇

PO (Adults ): Anaerobic infections: 7.5 mg/kg every 6 hr (not to exceed 4 g/day). Trichomoniasis: 250 mg every 8 hr for 7 days or single 2-g dose or 1 g twice daily for 1 day. Amebiasis: 500–750 mg every 8 hr for 5–10 days. H. pylori
: 250 mg 4 times daily or 500 mg twice daily for 1–2 wk (with other agents). Antibiotic associated
Clostridioides difficile
-associated diarrhea (CDAD): 250–500 mg 3–4 times/day for 10–14 days.
PO (Infants and Children): Anaerobic infections: 30 mg/kg/day divided every 6 hr, maximum dose: 4 g/day Trichomoniasis: 15–30 mg/kg/day divided every 8 hr for 7–10 days. Amebiasis: 35–50 mg/kg/day divided every 8 hr for 5–10 days (not to exceed 750 mg/dose). Clostridioides difficile
-associated diarrhea (CDAD): 30 mg/kg/day divided every 6 hr for 7–10 days. H. pylori
: 15–20 mg/kg/day divided twice daily for 4 wk.
IV PO (Neonates 0–4 wk, <1200 g): 7.5 mg/kg every 48 hr. Postnatal age <7 days, 1200–2000 g: 7.5 mg/kg/day every 24 hr. Postnatal age <7 days, >2000 g: 15 mg/kg/day divided every 12 hr. Postnatal age >7 days, 1200–2000 g: 15 mg/kg/day divided every 12 hr. Postnatal age >7 days, >2000 g: 30 mg/kg/day divided every 12 hr.
IV (Adults ): Anaerobic infections: Initial dose 15 mg/kg, then 7.5 mg/kg every 6–8 hr or 500 mg every 6–8 hr (not to exceed 4 g/day). Perioperative prophylaxis: Initial dose 15 mg/kg 1 hr before surgery, then 7.5 mg/kg 6 and 12 hr later. Amebiasis: 500–750 mg every 8 hr for 5–10 days.
IV (Children ): Anaerobic infections: 30 mg/kg/day divided every 6 hr, maximum dose: 4 g/day.
(Adults ): Acne rosacea: Apply thin film to affected area bid.
(Adults ): 0.75% vaginal gel: One applicatorful (37.5 mg) of 0.75% gel 1–2 times daily for 5 days; Nuvessa: One applicatorful (65 mg) of 1.3% gel as a single dose at bedtime; Vandazole: One applicatorful (37.5 mg) of 0.75% gel once daily for 5 days.
(Children ≥12 yr): Nuvessa: One applicatorful (65 mg) of 1.3% gel as a single dose at bedtime.
(Children Postmenarchal): Vandazole: One applicatorful (37.5 mg) of 0.75% gel once daily for 5 days.

Availability ⬆ ⬇

(Generic available)

Tablets: 250 mg; 500 mg
Capsules: 375 mg; 500 mg
Oral suspension (Likmez) strawberry-peppermint flavor: 500 mg/5 mL
Premixed infusion: 500 mg/100 mL
Topical cream: 0.75%; 1%
Topical gel: 0.75%; 1%
Topical lotion: 0.75%
Vaginal cream: 10% (500 mg/applicatorful)
Vaginal gel: 0.75% (37.5 mg/5 g applicatorful); 1.3% (65 mg/5 g applicatorful)
In combination with: bismuth subcitrate potassium and tetracycline (Pylera). See Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
- Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
- Monitor neurologic status during and after IV infusion.
- Monitor intake, output, and daily weight, especially for patients on sodium restriction. Each 500 mg of premixed injection for dilution contains 14 mEq of sodium.
- Assess for rash periodically during therapy. May cause SJS, AGEP, and TEN. Discontinue therapy if severe or if accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Giardiasis: Monitor three stool samples taken several days apart, beginning 3–4 wk after treatment.

Lab Test Considerations:

May alter results of serum AST, ALT, and LDH tests.
- Monitor CBC before, during, and after prolonged or repeated courses of metronidazole.

Implementation ⬆ ⬇

Do not confuse metronidazole with metformin.
PO: Administer on an empty stomach, or may administer with food or milk to minimize GI irritation. Tablets may be crushed for patients with difficulty swallowing. DNC: Swallow extended-release tablets whole; do not break, crush, or chew.Oral suspension is stable for 60 days after opening.
Cleanse affected area before application. Apply and rub in a thin film twice daily, morning and evening. Avoid contact with eyes.
Administer once daily dosing at bedtime.

IV Administration:

Intermittent Infusion: Diluent: Administer premixed injection (500 mg/100 mL) undiluted. Do not refrigerate. Once taken out of overwrap, premixed infusion stable for 30 days at room temperature.Concentration: 5 mg/mL.
Rate: Infuse over 30–60 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed , even if feeling better. Do not double up on missed doses; take as soon as remembered if not almost time for next dose.
Advise patients treated for trichomoniasis that sexual partners may be asymptomatic sources of reinfection and should be treated concurrently. Patient should also refrain from intercourse or use a condom to prevent reinfection.
Caution patient to avoid intake of alcoholic beverages or preparations containing alcohol during and for ≥3 days after treatment with metronidazole, including vaginal gel. May cause serious disulfiram-like reaction (flushing, nausea, vomiting, headache, abdominal cramps).
May cause dizziness or light-headedness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Instruct patient to notify health care professional promptly if rash occurs.
Advise patient to notify health care professional if numbness, tingling, weakness or seizures occur.
Inform patient that medication may cause an unpleasant metallic taste.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Advise patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may minimize dry mouth. Notify health care professional if dry mouth persists for >2 wk.
Inform patient that medication may cause urine to turn dark.
Advise patient to consult health care professional if no improvement in a few days or if signs and symptoms of superinfection (black, furry overgrowth on tongue; vaginal itching or discharge; loose or foul-smelling stools) develop.
Rep: Advise females of reproductive potential to inform health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
Instruct patient in correct technique for intravaginal instillation. Advise patient to avoid intercourse during treatment with vaginal gel.
Instruct patient on correct technique for application of topical gel. Cosmetics may be used after application of gel.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇