Metronidazole Topical

Absorption

Bioavailability

Absorbed systemically following topical application to skin; extent of absorption depends on formulation used (cream, gel, lotion).1 2 9 10 21 47 207

Absorbed systemically following intravaginal administration;119 131 132 183 214 systemic bioavailability of vaginal gel averages 50–56%.119 131 132 183 186

Following repeated topical application to the face of 1% cream (approximately 3.75 mg per dose) in adults with rosacea, serum concentrations were minimal or undetectable.9 Following topical application to the face of 1 g of 1% cream in healthy individuals, serum concentrations were minimal or undetectable and peak serum concentrations were attained within 8–12 hours after the dose.184

Following topical application to the face of 1 g of 1% topical gel in adults with rosacea, peak serum concentrations of metronidazole were attained 6–10 hours after the dose and were <1% of concentrations reported with a single 250-mg oral dose.1

Following topical application to the face of 1 g of 0.75% topical lotion (approximately 7.5 mg of metronidazole) twice daily for 4 days, drug was detectable in plasma of all patients and peak plasma concentrations were approximately 80 times lower than peak concentrations attained with a single 250-mg oral dose.207

Following intravaginal administration of 5 g of 0.75% vaginal gel (approximately 37.5 mg of metronidazole) in healthy women, peak serum concentrations were attained 4–17 hours after the dose and were approximately 2% of that attained after a single 500-mg oral dose.119 132 183 186 214

Distribution

Extent

Not fully characterized following topical application to skin10 or intravaginal administration.176 177

Crosses placenta following oral or IV administration;1 30 45 56 131 180 183 184 207 not known whether crosses placenta following topical application to skin1 or intravaginal administration.183

Distributed into milk following oral or IV administration;1 30 45 56 131 180 183 184 207 214 not known whether distributed into milk following topical application to skin1 or intravaginal administration.183

Elimination

Metabolism

Not fully characterized following topical application to skin10 or intravaginal administration.176 177

Elimination Route

Any systemically absorbed drug probably metabolized in liver and excreted in urine.10 61

In the U.S.

• Metrocream
• Metrogel
• Metrolotion
• Noritate
• Rosadan
• Rosadan Cream Kit
• Rozex
• Vitazol

Available Dosage Forms:

• Cream
• Lotion
• Gel/Jelly
• Emulsion

Therapeutic Class: Antiacne Antibacterial

Chemical Class: Nitroimidazole

Topical metronidazole is applied to the skin in adults to help control rosacea , also known as acne rosacea and “adult acne.” metronidazole helps to reduce the redness of the skin and the number of pimples, usually found on the face, in patients with rosacea.

Topical metronidazole is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dry skin
• redness or other signs of skin irritation not present before use of metronidazole
• stinging or burning of the skin
• watering of eyes

• Metallic taste in the mouth
• nausea
• tingling or numbness of arms, legs, hands, or feet

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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Bacterial vaginosis: Vaginal gel: Treatment of bacterial vaginosis

Rosacea: Topical: Treatment of inflammatory lesions and erythema of rosacea

Trichomoniasis: Flagyl cream [Canadian product]: Treatment of trichomoniasis in females

Bacterial vaginosis: Intravaginal:

0.75% (Vandazole): One applicatorful (~37.5 mg metronidazole) intravaginally once daily for 5 days

0.75% (MetroGel-vaginal, other products): One applicatorful (~37.5 mg metronidazole) intravaginally once or twice daily for 5 days

1.3%: One applicatorful (~65 mg metronidazole) intravaginally as a single dose

Rosacea: Topical:

0.75%: Apply and rub a thin film twice daily, morning and evening, to entire affected areas after washing.

1%: Apply thin film to affected area once daily

Trichomoniasis: Intravaginal: 10% (Flagyl Cream [Canadian product]): Insert one applicatorful (equal to metronidazole 500 mg) intravaginally once or twice daily for 10 or 20 consecutive days (even during menses)

Topical cream, gel, lotion: Store at 20°C to 25°C (68°F to 77°F).

Vaginal gel: Store at 15°C to 30°C (59°F to 86°F); do not refrigerate or freeze. Avoid exposure to extreme heat.

Concerns related to adverse effects:

• Carcinogenic: Possibly carcinogenic based on animal data. Unnecessary use should be avoided.

• CNS effects: Aseptic meningitis, encephalopathy, seizures, and neuropathies (peripheral and optic) have been reported with systemic metronidazole, especially with increased doses and chronic treatment; peripheral neuropathy has also been reported with topical products; monitor and consider discontinuation of therapy if signs/symptoms occur. Use with caution in patients with CNS diseases. Discontinue immediately if abnormal neurologic signs develop.

• Eye irritation: May cause tearing of the eye; avoid contact with the eyes. In the event of accidental contact, wash out immediately.

• Hepatic impairment: Use with caution in patients with severe liver impairment due to potential accumulation.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection. Approximately 6% to 10% of women treated with the vaginal gel developed Candida vaginitis during or immediately after treatment.

Disease-related concerns:

• Blood dyscrasias: Use with caution in patients with or history of blood dyscrasias.

Dosage form related concerns:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

• Vaginal gel: Disulfiram-like reaction to ethanol has been reported with systemic metronidazole and may occur with the vaginal gel; consider avoidance of alcoholic beverages during therapy with vaginal gel. Do not administer the vaginal gel to patients who have taken disulfiram within the past 2 weeks. Patients should avoid vaginal intercourse during treatment.

Do not take by mouth. Metronidazole topical is for use only on the skin. If this medication gets in your eyes, rinse with water.

Do not use topical metronidazole in the vagina.