Stiefel Ireland

Isotrex Gel 0.05% w/w Gel

Isotretinoin 0.05 % w/w

Excipients: contains butylated hydroxytoluene (E321) 0.01% w/w.

For a full list of excipients, see section 6.1.

Gel

A soft, greenish yellow gel with an odour of ethanol

Isotrex Gel is indicated for the topical treatment of mild to moderate inflammatory and non-inflammatory acne vulgaris.

Apply Isotrex Gel sparingly over the whole affected area once or twice daily.

Patients should be advised that 6-8 weeks of treatment may be required before a therapeutic effect is observed.

Paediatric use

The safety and efficacy of Isotrex Gel has not been established in children since acne vulgaris rarely presents in this age group.

Elderly Patients

There are no specific recommendations. Acne vulgaris does not present in the elderly.

Isotrex Gel should not be used in patients with known hypersensitivity to any of the ingredients.

Contact with the mouth, eyes and mucous membranes and with abraded or eczematous skin should be avoided; the product should not be allowed to accumulate in the angles of the nose. Butylated hydroxytoluene may cause local skin reactions (e.g.contact dermatitis), or irritation to the eyes and mucous membranes.

Application to sensitive areas of the skin, such as the neck, should be made with caution.

Albino mice treated with isotretinoin and exposed to ultraviolet light (artificial sunlight) demonstrated an accelerated appearance of sunlight induced skin tumours; mice treated with isotretinoin but not exposed to UV light did not develop tumours. The significance of these findings as related to man is unknown. Nevertheless it is recommended that Isotrex Gel should not be used in patients with a personal or family history of cutaneous epithelioma. Exposure to sunlight of areas treated with Isotrex Gel should be avoided or minimised. When exposure to strong sunlight cannot be avoided a sunscreen product and protective clothing should be used. Patients with sunburn should not use Isotrex gel due to the possibility of increased sensitivity to sunlight. The use of sunlamps should be avoided during treatment.

Concomitant topical medication should be used with caution during therapy with Isotrex Gel. Particular caution should be exercised when using preparations containing a peeling agent (for example benzoyl peroxide) or abrasive cleansers because of cumulative irritant effects.

There is inadequate evidence of the safety of topically applied isotretinoin in human pregnancy.

Isotretinoin has been associated with teratogenicity in humans when administered systemically. Reproduction studies conducted in rabbits using Isotrex Gel applied topicaly at up to 60 times the human dose have, however, revealed no harm to the foetus. The use of Isotrex Gel should be avoided during pregnancy.

Percutaneous absorption of isotretinoin from Isotrex Gel is negligible. It is not known, however, whether isotretinoin is excreted in human milk. Isotrex Gel should not be used during lactation.

None.

In normal use, Isotrex Gel may cause stinging, burning or irritation; erythema and peeling at the site of application may occur.

If undue irritation occurs, treatment should be interrupted temporarily and resumed once the reaction subsides. If irritation persists, treatment should be discontinued. Reactions will normally resolve on discontinuation of therapy.

Acute overdosage of Isotrex Gel has not been reported to date. Accidental ingestion of Isotrex Gel resulting in overdosage of isotretinoin could be expected to induce symptoms of hypervitaminosis A. These include severe headaches, nausea or vomiting; drowsiness, irritability and pruritus.

Isotretinoin is structurally and pharmacologically related to Vitamin A which regulates epithelial cell growth and differentiation.

The pharmacological action of isotretinoin remains to be fully elucidated. When used systemically it suppresses sebaceous gland activity and reduces sebum production; it also affects comedogenesis, suppresses Propionibacterium acnes and reduces inflammation.

When applied topically, the mode of action of isotretinoin is probably comparable with its stereoisomer, tretinoin. Tretinoin stumulates mitosis in the epidermis and reduces intercellular cohesion in the stratum corneum; it contests the hyperkeratosis characteristic of acne vulgaris and aids desquamation, preventing the formation of lesions. Tretinoin also mediates an increased production of less cohesive epidermal sebaceous cells, this appears to promote the initial expulsion and subsequent prevention of comedones.

Animal studies have demonstrated that topical isotretinoin elicits epidermal hyperplasia reduces hyperkeratosis and suppresses sebum production and sebaceous gland size. The anti-inflammatory action of isotretinoin when applied topically has been confirmed in man.

Percutaneous absorption of isotretinoin from the gel is negligible. After applying 20g per day of isotretinoin 0.05% gel to acne of the face, chest and back for 30 days, HPLC assays for isotretinoin and tretinoin demonstrated non-detectable levels in the plasma samples (<0.02μg/ml). Applying ¹⁴C isotretinoin in a cream base on the healthy skin of volunteers resulted in only 0.03% of the topically applied dose being recovered through estimating the radioactivity of blood, urine and faecal samples.

The relevant information is given in Section 4.

Butylated hydroxytoluene (E321)

Hydroxypropylcellulose

Ethanol

Not applicable.

Unopened: 3 years

Once opened: use within 2 months after first opening the tube and discard any unused portion.

Store below 25°C. Replace cap securely after use.

Internally lacquered membrane-sealed aluminium tubes fitted with a polypropylene screw-cap, packed into a carton. Pack contents: 30g.

No special requirements.

GlaxoSmithKline (Ireland) Ltd

Stonemasons Way

Rathfarnham

Dublin 16

Ireland

Trading as Stiefel

PA 1077/122/001

Date of first authorisation: 18^th August 1992

Date of last renewal: 18^th August 2007

3^rd December 2010