Metrogel

Metronidazole BP 0.75%.

Aqueous gel for cutaneous use.

For the treatment of acute inflammatory exacerbation of rosacea.

For the deodorisation of the smell associated with malodorous fungating tumours.

For the treatment of rosacea:

Adults and elderly:

Apply to the affected skin of the face in a thin film twice daily for a period of eight to nine weeks. Thereafter, further applications may be necessary depending upon the severity of the condition.

Children:

Not recommended.

For the deodorisation of malodorous fungating tumours:

Adults and elderly:

Clean the wound thoroughly. Apply the gel over the complete area and cover with a non-adherent dressing. Use once or twice daily as necessary.

Children:

Not recommended.

Contraindicated in individuals with a history of hypersensitivity to Metronidazole, or other ingredients of the formulation.

Metrogel has been reported to cause lacrimation of the eyes, therefore, contact with the eyes should be avoided. If a reaction suggesting local irritation occurs patients should be directed to use the medication less frequently, discontinue use temporarily or discontinue use until further instructions. Metronidazole is a nitroimidazole and should be used with care in patients with evidence of, or history of, blood dyscrasia. Exposure of treated sites to ultraviolet or strong sunlight should be avoided during use of metronidazole.

Unnecessary and prolonged use of this medication should be avoided.

Interaction with systemic medication is unlikely because absorption of metronidazole following cutaneous application of Metrogel is low. Oral metronidazole has been reported to potentiate the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The effect of topical metronidazole on prothrombin is not known. However, very rare cases of modification of the INR values have been reported with concomitant use of Metrogel and coumarin anticoagulants.

The safety of metronidazole in pregnancy and lactation had not been adequately established. The gel should therefore not be used in these circumstances unless the physician considers it essential. Medication should be stopped if pregnancy occurs.

None.

Because of the minimal absorption of metronidazole and consequently its insignificant plasma concentration after topical administration, the adverse experiences reported with the oral form of the drug have not been reported with Metrogel. Adverse reactions reported with Metrogel have been only local and mild, and include skin discomfort (burning and stinging), erythema, pruritis, skin irritation, worsening of rosacea, nausea, metallic taste and tingling or numbness of the extremities, and watery eyes if applied too closely to this area.

No data exists about overdosage in humans. Acute oral toxicity studies with a topical gel formulation containing 0.75% w/w metronidazole in rats have shown no toxic action with doses of up to 5 g of finished product per kilogram body weight, the highest dose used. This dose is equivalent to the oral intake of 12 tubes of 30g packaging Metrogel for an adult weighing 72 kg, and 2 tubes of Metrogel for a child weighing 12 kg.

The etiology of rosacea is unknown although a variety of hypotheses have been reported.

The systemic concentration of Metronidazole following the topical administration of 1 g of a 0.75% Metronidazole gel to 10 patients with rosacea ranged from 25 ng/ml (limit of detection), to 66 mg/ml with a mean Cmax of 40.6 ng/ml.

The corresponding mean Cmax following the oral administration of a solution containing 30 mg of metronidazole was 850 ng/ml (equivalent to 212 ng/ml if dose corrected. The mean Tmax for the topical formulation was 6.0 hours compared to 0.97 hours for the oral solution.

Metronidazole is a well established pharmaceutical active ingredient and to the subject of pharmacopoeial monograph in both the BP and Ph.Eur.

Bronopol BP,

Hydroxybenzoic acid esters HSE,

Hydroxyethylcellulose HSE,

Propylene glycol Ph.Eur,

Phosphoric acid Ph.Eur,

Purified water Ph.Eur.

None known

2 years.

Store between 15°C and 25°C in a dry place.

Tube: Internally lacquered, membrane sealed aluminium.

Cap: low density polyethylene

Pack sizes available: 25 g and 40 g.

There are no special instructions for use/handling.

Galderma (UK) Limited

Meridien House

69-71 Clarendon Road

Watford

Herts.

WD17 1DS

UK

PL 10590/0035

27 February 1998

February 2006

POM