METRONIDAZOLE

(me-troe-ni'da-zole)

Flagyl, Flagyl ER, Flagyl IV, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, Vandazole
Classifications: antitrichomonal; amebicide; azole antibiotic;
Therapeutic:amebicide; azole antibiotic
Pregnancy Category: B

Availability

250 mg, 500 mg tablets; 375 mg capsules; 750 mg sustained release tablets; 500 mg vials; 0.75% lotion, emulsion; 0.75%, 1% cream; 0.75%, 1% gel

Action

Synthetic compound with trichomonacidal and amebicidal activity as well as antibacterial activity against anaerobic bacteria and some gram-negative bacteria.

Therapeutic Effect

Has direct trichomonacidal and amebicidal activity; exhibits antibacterial activity against obligate anaerobic bacteria, gram-negative anaerobic bacilli, and Clostridia.

Uses

Asymptomatic and symptomatic trichomoniasis in females and males; acute intestinal amebiasis and amebic liver abscess; preoperative prophylaxis in colorectal surgery, elective hysterectomy or vaginal repair, and emergency appendectomy. IV metronidazole is used for the treatment of serious infections caused by susceptible anaerobic bacteria in intraabdominal infections, skin infections, gynecologic infections, septicemia, and for both pre- and postoperative prophylaxis, bacterial vaginosis. Topical: Rosacea.

Unlabeled Uses

Treatment of pseudomembranous colitis, Crohn's disease, H. pylori eradication.

Contraindications

Blood dyscrasias; active CNS disease; lactation.

Cautious Use

Coexistent candidiasis; seizure disorders; heart failure; older adults; severe hepatic disease; renal impairment/failure; pregnancy (category B); alcoholism; liver disease.

Route & Dosage

Trichomoniasis
Adult: PO 2 g once or 250 mg t.i.d. x 7 d
Child/Infant: PO 15–30 mg/kg/d q8h x 7 d

Giardiasis, Gardnerella
Adult: PO 500 mg b.i.d. x 7 d OR 750 ER tablet q.d. x 7 d Vaginal Once or twice daily x 5 d

Amebiasis
Adult: PO 500–750 mg t.i.d. x 5–10 d
Child: PO 35–50 mg/kg/d in 3 divided doses x 10 d

Anaerobic Infections
Adult: PO 7.5 mg/kg q6h (max: 4 g/d) IV Loading Dose 15 mg/kg IV Maintenance Dose 7.5 mg/kg q6h (max: 4 g/d)
Child: PO 15–35 mg/kg/d divided q8h (max: 4 g/d) IV 30 mg/kg/d divided q6h
Neonate: IV <1.2 kg, 7.5 mg q48h; <7 d/1.2 kg–2 kg, 7.5 mg q24h; <7 d/>2 kg, 15 mg/kg q12h; >7 d/1.2 kg–2 kg, 15 mg/kg q12h; >7 d/>2 kg, 30 mg/kg q12h

Pseudomembranous Colitis
Adult: PO 250–500 mg 3–4 times daily x 10 d

Rosacea
Adult: Topical Apply 0.75% gel as a thin film to affected area b.i.d.; apply 1% gel as a thin film to affected area q.d.

Administration

Oral

Crush tablets before ingestion if patient cannot swallow whole.
Ensure that Flagyl ER (extend-release form) is not chewed or crushed. It must be swallowed whole. Give on an empty stomach, 1 h before or 2 h after meals.
Give immediately before, with, or immediately after meals or with food or milk to reduce GI distress.
Give lower than normal doses in presence of liver disease.

Topical

Apply a thin film to affected area only.

Intravenous

Note: Verify correct IV concentration and rate of infusion for administration to neonates, infants, or children with physician.

PREPARE: Intermittent: Single-dose flexible containers (500 mg/100 mL) are ready for use without further dilution. Flagyl IV powder vial: Sequence for preparing solution (important) consists of (1) reconstitution with 4.4 mL sterile water or NS, (2) dilution in IV solution to yield 8 mg/mL in NS, D5W, or RL, (3) pH neutralization with approximately 5 mEq sodium bicarbonate injection for each 500 mg of Flagyl IV used. Avoid use of aluminum-containing equipment when manipulating IV product (including syringes equipped with aluminum needles or hubs).

ADMINISTER: Intermittent: Give IV solution slowly at a rate of one dose per hour.

INCOMPATIBILITIES Solution/additive: tpn, amoxicillin/clavulanate, aztreonam, dopamine. Y-site: Amphotericin B cholesteryl complex, aztreonam, filgrastim, meropenem, warfarin.

Note: Precipitation occurs if neutralized solution is refrigerated. Use diluted and neutralized solution within 24 h of preparation.

Store at 15°–30° C (59°–86° F); protect from light. Reconstituted Flagyl IV is chemically stable for 96 h when stored below 30° C (86° F) in room light. Diluted and neutralized IV solutions containing Flagyl IV should be used within 24 h of mixing.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (rash, urticaria, pruritus, flushing), fever, fleeting joint pains, overgrowth of Candida. CNS: Vertigo, headache, ataxia, confusion, irritability, depression, restlessness, weakness, fatigue, drowsiness, insomnia, paresthesias, sensory neuropathy (rare). GI: Nausea, vomiting, anorexia, epigastric distress, abdominal cramps, diarrhea, constipation, dry mouth, metallic or bitter taste, proctitis. Urogenital: Polyuria, dysuria, pyuria, incontinence, cystitis, decreased libido, dyspareunia, dryness of vagina and vulva, sense of pelvic pressure. Special Senses: Nasal congestion. CV: ECG changes (flattening of T wave).

Diagnostic Test Interference

Metronidazole may interfere with certain chemical analyses for AST, resulting in decreased values.

Interactions

Drug: oral anticoagulants potentiate hypoprothrombinemia; alcohol may elicit disulfiram reaction; oral solutions of citalopram, ritonavir; lopinavir/ritonavir, and IV formulations of sulfamethoxazole; trimethoprim, SMX-TMP, nitroglycerin may elicit disulfiram reaction due to the alcohol content of the dosage form; disulfiram causes acute psychosis; phenobarbital increases metronidazole metabolism; may increase lithium levels; fluorouracil, azathioprine may cause transient neutropenia.

Pharmacokinetics

Absorption: 80% absorbed from GI tract. Peak: 1–3 h. Distribution: Widely distributed to most body tissues, including CSF, bone, cerebral and hepatic abscesses; crosses placenta; distributed in breast milk. Metabolism: 30–60% in liver. Elimination: 77% in urine; 14% in feces within 24 h. Half-Life: 6–8 h.

Nursing Implications

Assessment & Drug Effects

Discontinue therapy immediately if symptoms of CNS toxicity (see Appendix F) develop. Monitor especially for seizures and peripheral neuropathy (e.g., numbness and paresthesia of extremities).
Lab tests: Obtain total and differential WBC counts before, during, and after therapy, especially if a second course is necessary.
Monitor for S&S of sodium retention, especially in patients on corticosteroid therapy or with a history of CHF.
Monitor patients on lithium for elevated lithium levels.
Report appearance of candidiasis or its becoming more prominent with therapy to physician promptly.
Repeat feces examinations, usually up to 3 mo, to ensure that amebae have been eliminated.

Patient & Family Education

Adhere closely to the established regimen without schedule interruption or changing the dose.
Refrain from intercourse during therapy for trichomoniasis unless male partner wears a condom to prevent reinfection.
Have sexual partners receive concurrent treatment. Asymptomatic trichomoniasis in the male is a frequent source of reinfection of the female.
Do not drink alcohol during therapy; may induce a disulfiram-type reaction (see Appendix F). Avoid alcohol or alcohol-containing medications for at least 48 h after treatment is completed.
Urine may appear dark or reddish brown (especially with higher than recommended doses). This appears to have no clinical significance.
Report symptoms of candidal overgrowth: Furry tongue, color changes of tongue, glossitis, stomatitis; vaginitis, curd-like, milky vaginal discharge; proctitis. Treatment with a candidacidal agent may be indicated.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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