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:

For topical administration only.

The average period of treatment is three to four months. The recommended duration of treatment should not be exceeded. However, if a clear benefit has been demonstrated, continued therapy for a further three to four months period may be considered by the prescribing physician depending on the severity of the condition. In clinical studies, topical metronidazole therapy for rosacea has been continued for up to 2 years. In the absence of a clear clinical improvement, therapy should be stopped.

Adults: Metrogel should be applied in a thin layer to the affected areas of the skin twice daily, morning and evening. Areas to be treated should be washed with a mild cleanser before application. Patients may use non-comedogenic and non-astringent cosmetics after application of Metrogel.

Elderly: The dosage recommended in the elderly is the same as that recommended in adults.

Children: Not recommended. Safety and efficacy have not been established.

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

Contact with mucous membranes should be avoided.

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 or discontinue use temporarily and to seek medical advice if necessary. 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 (e.g. solarium, sun-lamp) or strong sunlight (including sun-bathing) should be avoided during use of metronidazole.

Unnecessary and prolonged use of this medication should be avoided.

Evidence suggests that metronidazole is carcinogenic in certain animal species. There is no evidence to date of a carcinogenic effect in human.

This product contains propylene glycol that may cause skin irritation and hydroxybenzoic acid esters which may cause allergic reactions (possibly delayed).

Interaction with systemic medication is unlikely because absorption of metronidazole following cutaneous application of Metrogel is low. Nevertheless, it should be mentioned that disulfiram-like reactions have been reported in a small number of patients taking metronidazole and alcohol concomitantly. 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.

There has been no experience to date with the use of Metrogel in pregnant patients. In case of oral administration, metronidazole crosses the placental barrier and enters foetal circulation rapidly. No foetotoxicity was observed after oral metronidazole in either rats or mice. However because animal reproduction studies are not always predictive of human response and since oral metronidazole has been shown to be a carcinogen in some rodents this drug should be used in pregnancy only if clearly needed.

After oral administration metronidazole is secreted in breast milk in concentration similar to those found in plasma. Even though blood levels are significantly lower with cutaneous application of Metrogel than those achieved after oral metronidazole in nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into importance of the drug to the mother.

Based upon the pharmacodynamic profile and clinical experience performance related to driving and using machines should not be affected.

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.

The following spontaneous adverse experiences have been reported, and within each system

organ class, are ranked by frequency, using the following convention:

Very common (1/10)

Common (1/100, < 1/10)

Uncommon ( 1/ 1,000, < 1/100)

Rare (1/10,000, < 1/1,000)

Very rare (<1/10,000), including isolated reports

Skin and subcutaneous tissue disorders:

Common: dry skin, erythema, pruritus, skin discomfort (burning, pain of skin/stinging), skin irritation, worsening of rosacea.

Unknown frequency: contact dermatitis

Nervous System disorders:

Uncommon: hypothesia, paraesthesia, dysgeusia (metallic taste)

Gastrointestinal disorders:

Uncommon: nausea

Watery eyes have been reported 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

December 2010

POM