Metronidazole (Topical) (MetroGel, MetroCream, Noritate)

1. Health Canada Product Monograph — Metronidazole (Topical)

• Topical metronidazole is indicated for the treatment of inflammatory papules, pustules, and erythema of rosacea.
• Health Canada has not authorized a pediatric indication.

• There is no clinical experience with topical metronidazole specifically in pregnant patients. Metronidazole crosses the placenta and enters the fetal circulation rapidly, though no fetal harm was seen after oral metronidazole in animal studies.
• Use only after careful assessment of the risk/benefit ratio, since animal studies are not always predictive of the human response.

• After oral dosing, metronidazole is secreted into breast milk in concentrations similar to plasma; blood levels after topical application are substantially lower than after oral dosing.
• A decision should be made whether to discontinue nursing or discontinue the drug, taking into account its importance to the mother.

• 66 patients aged 65 and older were treated with the 1% gel over 10 weeks in trials, with comparable safety and efficacy to the general study population.

• No data are available to Health Canada; a pediatric indication has not been authorized.

• 1% strength: apply and rub in a thin film once daily to the entire affected area.
• 0.75% strength: apply and rub in a thin film twice daily (morning and evening) to the entire affected area.
• Cleanse and dry the face before application. Cosmetics may be applied once the medication has absorbed ("dried") into the skin.
• Significant improvement is usually seen within 3 weeks, with continuing improvement reported through 9 weeks; the dose/duration needed for longer-term maintenance beyond that has not been established.
• If a dose is missed, apply as soon as possible; if it is almost time for the next dose, skip the missed one and resume the regular schedule.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No human overdose experience exists. Topically applied metronidazole can be absorbed in sufficient amount to cause systemic effects if the recommended dose/duration is exceeded.
• Massive ingestion may cause vomiting and slight disorientation; there is no specific antidote. Activated charcoal may help remove unabsorbed drug, and general supportive care is recommended. Contact your regional Poison Control Centre for any suspected overdose.

• Dry skin, redness (erythema), itching (pruritus), and a burning sensation are the most common effects, each generally occurring in under 1% of patients and mild to moderate in severity.
• Skin irritation, papular rash, skin peeling (desquamation), skin tightness, and increased tearing of the eyes have also been reported.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Facial swelling and hives have been reported uncommonly.
• Conjunctivitis has been reported with facial application, and eye contact can cause tearing -- avoid the eyes.
• Contact dermatitis/allergic reaction has been reported post-marketing; watch for cross-sensitivity with other imidazole antifungals (e.g., clotrimazole, tioconazole).
• Seek medical attention for facial swelling, widespread hives, or severe skin irritation that does not improve.

• Avoid contact with the eyes; flush with water if contact occurs. Do not use in or close to the eyes.
• Use with care in patients with a history of blood dyscrasia, since metronidazole is a nitroimidazole.
• Minimize sun and tanning-bed exposure while using this product.
• Reduce frequency, interrupt use, or stop if local irritation develops.
• Must not be used in patients with Cockayne syndrome -- cases of severe, sometimes fatal, liver toxicity have been reported with metronidazole-containing products (based on data with systemic metronidazole) in this population.
• Should only be used for the authorized indication, to reduce the risk of contributing to antimicrobial resistance.

• Hypersensitivity to metronidazole or any ingredient in the formulation.
• Cockayne syndrome.

• Systemic exposure after topical use is roughly 100-fold lower than after a single oral 250 mg dose, so significant interactions with systemic medications are unlikely, but caution is still reasonable.
• Coumarin/warfarin: topical use is less likely to interact than oral use, but the potentiation of anticoagulant effect seen with oral metronidazole should be kept in mind in patients on anticoagulants.
• Alcohol: a disulfiram-like reaction is a well-documented interaction with oral metronidazole; this has not been reported with topical use, but the possibility exists and patients should be informed.
• Other imidazole preparations (e.g., clotrimazole, tioconazole): possible skin cross-sensitivity.

• No food interactions have been established.

• Apply once daily (1% strength) or twice daily, morning and evening (0.75% strength), to clean, dry skin.

• Store at room temperature (15°C to 30°C).

• This topical gel/cream treats the bumps, pimples, and redness of rosacea when applied regularly to clean, dry skin.
• Expect noticeable improvement by about 3 weeks, with continued improvement over the following weeks -- don't stop early if results seem slow.
• This is not the same product as metronidazole tablets or vaginal gel -- do not substitute between them.
• Avoid the eyes; rinse with water if you get product in your eyes, and expect some tearing if this happens.
• Avoid alcohol as a precaution, since a reaction similar to the one seen with metronidazole tablets is theoretically possible with the topical form.