metronidazole hydrochloride

metronidazole hydrochloride Warning - Hazardous drug!

Pharmacologic class: Nitroimidazole derivative

Therapeutic class: Anti-infective, antiprotozoal

Pregnancy risk category B

FDA Boxed Warning

• Drug is carcinogenic in mice and rats. Avoid unnecessary use; reserve drug for indicated conditions.

Action

Disturbs DNA synthesis in susceptible bacterial organisms

Availability

Capsules: 375 mg

Powder for injection: 5 mg/ml, 500-mg vials

Premixed injection: 500 mg/100 ml

Tablets: 250 mg, 500 mg

Tablets (extended-release): 750 mg

Topical cream, topical gel: 0.75% in 28.4-g tubes

Topical lotion: 0.75% in 59-ml bottle

Vaginal gel: 0.75% (37.5 mg/5-g applicator) in 70-g tubes

⊘Indications and dosages

➣ Trichomoniasis

Adults: 2 g P.O. as a single dose or in two 1-g doses given on same day. Alternatively, 500 mg P.O. b.i.d. for 7 days.

➣ Bacterial infections

Adults: Initially, 15 mg/kg I.V., followed by 7.5 mg/kg I.V. q 6 hours, not to exceed 4 g/day for 7 to 10 days

➣ Amebiasis

Adults: 750 mg P.O. q 8 hours for 5 to 10 days

➣ Amebic liver abscess

Adults: 500 to 750 mg P.O. t.i.d. for 5 to 10 days. If drug can't be given orally, administer 500 mg I.V. q 6 hours for 10 days.

Children: 35 to 50 mg/kg/day P.O. in three divided doses for 10 days, to a maximum of 750 mg/dose

➣ Bacterial vaginosis

Adults: In nonpregnant patients, 750 mg/day P.O. (extended-release) for 7 days or 5 g of 0.75% vaginal gel b.i.d. for 5 days. In pregnant patients, 250 mg P.O. t.i.d. for 7 days.

➣ Perioperative prophylaxis in colorectal surgery

Adults: Initially, 15 mg/kg I.V. infusion over 30 to 60 minutes, completed 1 hour before surgery; if necessary, 7.5 mg/kg I.V. infusion over 30 to 60 minutes at 6 and 12 hours after initial dose

➣ Rosacea

Adults: Rub a thin layer of topical lotion, gel, or cream onto entire affected area morning and evening. Improvement should occur within 3 weeks.

Contraindications

• Hypersensitivity to drug, other nitroimidazole derivatives, or parabens (topical form only)
• First-trimester pregnancy in patients with trichomoniasis

Precautions

Use cautiously in:
• severe hepatic impairment
• history of blood dyscrasias, seizures, or other neurologic problems
• breastfeeding patients
• children.

Administration

• Reconstitute powder for injection by adding 4.4 ml of sterile or bacteriostatic water for injection, 0.9% sodium chloride injection, or bacteriostatic sodium chloride injection to 500-mg vial. Further dilute resulting concentration (100 mg/ml) in 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection solution to a concentration of 8 mg/ml or less. Infuse each I.V. dose over 1 hour.
• Be aware that for I.V. injection, drug need not be diluted or neutralized.
• Don't use equipment containing aluminum to reconstitute or transfer reconstituted solution to diluent; solution may turn reddish-brown.
• Don't interchange vaginal gel with topical gel, cream, or lotion.

Route	Onset	Peak	Duration
P.O.	Rapid	1-3 hr	8 hr
P.O. (extended)	Rapid	Unknown	Up to 24 hr
I.V.	Rapid	End of infusion	6-8 hr
Topical	Unknown	6-12 hr	Unknown
Vaginal	Unknown	6-12 hr	12 hr

Adverse reactions

CNS: dizziness, headache, ataxia, vertigo, incoordination, insomnia, fatigue

EENT: rhinitis, sinusitis, pharyngitis

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

GU: dysuria, dark urine, incontinence

Hematologic: leukopenia

Skin: rash, urticaria, burning, mild skin dryness, skin irritation, transient redness (with topical forms)

Other: unpleasant or metallic taste, superinfection, phlebitis at I.V. site

Interactions

Drug-drug. Azathioprine, fluorouracil: increased risk of leukopenia

Cimetidine: decreased metronidazole metabolism, increased risk of toxicity

Disulfiram: acute psychosis and confusion

Lithium: increased lithium blood level

Phenobarbital: increased metronidazole metabolism, decreased efficacy

Warfarin: increased warfarin effects

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase: altered levels

Drug-behaviors. Alcohol use: disulfiram-like reaction

Patient monitoring

• Monitor I.V. site. Avoid prolonged use of indwelling catheter.
• Evaluate hematologic studies, especially in patients with history of blood dyscrasias.

Patient teaching

• Advise patient to take drug with food if it causes GI upset. However, instruct him to take extended-release tablets 1 hour before or 2 hours after meals.
• Tell patient with trichomoniasis to refrain from sexual intercourse or to have male partner wear a condom to prevent reinfection. Explain that asymptomatic sex partners should be treated simultaneously.
• Advise patient to report fever, sore throat, bleeding, or bruising.
• Inform patient that drug may cause metallic taste and may discolor urine deep brownish-red.
• Tell patient using topical form to clean area thoroughly with mild cleanser before use and then wait 15 to 20 minutes before applying drug. Tell her she may apply cosmetics to skin after applying drug; with topical lotion, instruct her to let skin dry at least 5 minutes before applying cosmetics.
• Tell female patient to consult prescriber if she is pregnant or plans to become pregnant.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.