Helsinn Birex Therapeutics Ltd

Aulin 3% w/w Gel.

Aulin 3% w/w gel contains 3% w/w nimesulide (1 g of gel contains 30 mg of nimesulide)

For excipients, see section 6.1

Gel

Opalescent, pale yellow gel

Symptomatic relief of pain associated with sprains and acute traumatic tendinitis.

Adults: Aulin 3% w/w gel (usually 3 g, corresponding to a line 6-7 cm long) should be applied in a thin layer to the affected area 2-3 times daily and massaged until it is completely absorbed.

Duration of treatment: 7 – 15 days.

Childrenunder 12 years: Aulin 3% w/w gel has not been studied in children. Therefore, safety and efficacy have not been established and the product should not be used in children (see section 4.3).

Known hypersensitivity to nimesulide or to any other excipients in the gel.

Use in patients in whom aspirin, or other medicinal products inhibiting prostaglandin synthesis, induced allergic reactions such as rhinitis, urticaria or bronchospasm.

Use on broken or denuded skin or in the presence of local infection.

Simultaneous use with other topical creams.

Use in children under 12 years.

Aulin 3% w/w gel should not be applied to skin wounds or open injuries.

Aulin 3% w/w gel should not be allowed to come into contact with the eyes or mucous membranes; in case of accidental contact, wash immediately with water.

The product should never be taken by mouth. Hands should be washed after applying the product.

Aulin 3% w/w gel should not be used with occlusive dressings.

Aulin 3% w/w gel is not recommended for use in children under 12 years (see section 4.3).

Undesirable effects may be reduced by using the minimum effective dose for the shortest possible duration.

Patients with gastro-intestinal bleeding, active or suspected peptic ulcer, severe renal or hepatic dysfunction, severe coagulation disorders or severe/non controlled heart failure should be treated with caution.

Since Aulin 3% w/w gel has not been studied in hypersensitive subjects, particular caution should be used when treating patients with known hypersensitivity to other NSAIDs. The possibility of developing hypersensitivity in the course of therapy cannot be excluded.

Since with other topical NSAIDs burning sensation and exceptionally photodermatitis can occur, care should be taken during treatment with Aulin 3% w/w gel.

To reduce the risk of photosensitivity, patients should be warned against exposure to direct and solarium sunlight.

If symptoms persist or the condition is aggravated medical advice should be sought.

No interactions of Aulin 3% w/w gel with other medicinal products are known or to be expected via the topical route.

There are no data relevant to the topical use of Aulin gel in pregnant women or during breastfeeding. Therefore, Aulin 3% w/w gel should not be used during pregnancy or lactation unless clearly necessary.

No studies on the effect of Aulin 3% w/w gel on the ability to drive and use machines have been performed.

The following side effects listing is based on reports from clinical studies, in a limited number of patients, where mild local reactions have been reported. The reporting rates are classified as: 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 cases.

Intoxication with nimesulide as a result of topical application of Aulin 3% w/w gel is not to be expected since the highest plasma levels of nimesulide following application of Aulin 3% w/w gel are far below those found following systemic administration.

Pharmacotherapeutic group: ATC code: M02AA.

Non-steroidal anti-inflammatory drug (NSAID) for topical use.

Nimesulide is an inhibitor of the prostaglandin synthesis enzyme cyclo-oxygenase.

Cyclo-oxygenase produces prostaglandins, some of them being implicated in the development and maintenance of inflammation.

When Nimesulide 3% gel is applied topically, plasma concentrations of nimesulide are very low in comparison with those achieved following oral intake. After a single application of 200mg of nimesulide, in the gel form, the highest plasma level of 9.77 ng/ml was noted after 24 hours. No trace of the main metabolite 4-hydroxy-nimesulide, was detected. At steady-state (day 8) peak plasma concentrations were higher (37.25 ± 13.25 ng/ml, but almost 100 times lower than those measured following repeated oral administration.

The local tolerance and the irritation and sensitisation potential of Nimesulide 3% gel have been tested in several recognised animal models. The results of these studies indicate that Nimesulide 3% gel is well tolerated.

Preclinical data for systemically administered nimesulide reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. In repeated dose toxicity studies, nimesulide showed gastrointestinal, renal and hepatic toxicity. In reproductive toxicity studies, embryotoxic and teratogenic effects (skeletal malformations, dilatation of cerebral ventricles) were observed in rabbits, but not in rats, at maternally non-toxic dose levels. In rats, increased mortality of offspring was observed in the early postnatal period and nimesulide showed adverse effects on fertility.

Purified water

Diethylene glycol monoethyl ether

Caprylcaproyl macrogol glycerides

Carbomers

Disodium edetate

Triethanolamine

Methyl-parahydroxybenzoate

Propyl-parahydroxybenzoate

Not applicable.

2 years.

Do not store above 30°C.

15g, 30g, 50g and 100g aluminium tubes lined with lacquer made of an epoxyphenolic resin and closed with a polypropylene cap.

6.6 Instructions for Use/Handling

Wash hands after use.

HELSINN BIREX PHARMACEUTICALS Ltd.

Damastown

Mulhuddart

Dublin 15,

PA 294/18/3

July 2004