NAME OF THE MEDICINAL PRODUCT

Metrogel 0.75% w/w Gel

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Metronidazole 0.75%.

Excipients with known effect:

Propylene glycol 5% w/w Hvdroxvbenzoic acid esters 0.13% w/w

For the full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Aqueous gel for cutaneous use

4.    CLINICAL PARTICULARS

4.1_Therapeutic indications

For the treatment of acute inflammatory exacerbation of rosacea.

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

4.2_Posologv and method of administration

For the treatment of rosacea:

Posologv

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.

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

Paediatric population: Not recommended. Safety and efficacy have not been established.

Method of administration

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.

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.

Breast-feeding

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.

4.7_Effects on ability to drive and use machines

Metrogel has no influence on the ability to drive and use machines.

4.8_Undesirable effects

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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.

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Watery eves have been reported if applied too closely to this area.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard

4.9. Overdose

No data exists about overdose 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.

5. PHARMACOLOGICAL PROPERTIES

5.1_Pharmacodynamic properties

Pharmacotherapeutic Group: Chemotherapeutics for external use ATC code: D06BX01

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

5.2_Pharmacokinetic properties

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.

5.3_Preclinical safety data

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

6.    PHARMACEUTICAL PARTICULARS

6.1_List of excipients

Bronopol BP,

Hydroxybenzoic acid esters,

Hvdroxvethvlcellulose.

Propylene glycol,

Phosphoric acid.

Purified water.

6.2_Incompatibilities

Not applicable

Shelf life

2 years.

6.4_Special precautions for storage

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

6.5_Nature and contents of container

Tube: Internally lacquered, membrane sealed aluminium. Cap: low density polyethylene Pack sizes: 25 g and 40 g.

Not all pack sizes may be marketed.

6.6_Special precautions for disposal and other handling

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Galderma (UK) Limited Meridien House 69-71 Clarendon Road Watford Herts.

WD17 1DS UK

8.    MARKETING AUTHORISATION NUMBER

PL 10590/0035

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 27 February 1998

10 DATE OF REVISION OF THE TEXT

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