Isotrex Gel

Isotretinoin 0.05% w/w

For excipients, see 6.1.

Gel for topical application

Isotrex Gel is intended for use in the treatment of mild to moderate inflammatory and non-flammatory 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.

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

There are no specific recommendations for use in the elderly. 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. Care should be taken not to let the medication accumulate in skin fold areas and in the angles of the nose.

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

Although tretinoin has not been shown to initiate or promote carcinogenesis in humans, tretinoin applied topically to albino hairless mice had resulted in a dose-related acceleration in ultraviolet-B radiation induced cutaneous tumours. The same author also observed the opposite effect in another study of low, non-irritating concentrations of tretinoin. The significance of these findings as related to man is unknown; however, caution should be observed 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.

Category B1.

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 topically 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.

Use during lactation

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.

Not applicable; the product is a topical preparation which acts locally at the site of application.

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 may be comparable with its stereoisomer, tretinoin. Tretinoin stimulates 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.

Percutaneous absorption of isotretinoin from the gel is negligible. After applying 30g 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 human volunteers resulted in only 0.03% of the topically applied dose being recovered through estimating the radioactivity of blood, urine and faecal samples

Not applicable. The relevant information is given in Section 4.

Butylated Hydroxytoluene

Hydroxypropylcellulose

Ethanol

Not applicable.

a) For the product as packaged for sale

3 years

b) After first opening the container

Two months

Store below 25°C

Aluminium tube of 5g, 15g, 25g, 30g, 50g, 60g fitted with a screw cap.

There are no special instructions for use or handling of Isotrex Gel.

GlaxoSmithKline UK Limited

980 Great West Road

Brentford

Middlesex

TW8 9GS

Trading as Stiefel

Stockley Park West

Uxbridge

Middlesex

UB11 1BT

PL 19494/0063

20/12/2005

14 December 2010