Lamisil AT 1% Gel

1. Name Of The Medicinal Product

Lamisil® AT 1% Gel

2. Qualitative And Quantitative Composition

Terbinafine 1.0 % w/w

For excipients, see Section 6.1.

3. Pharmaceutical Form

Gel

4. Clinical Particulars

4.1 Therapeutic Indications

The treatment of tinea pedis (athlete's foot), tinea cruris (dhobie (jock) itch) and tinea corporis (ringworm) caused by Trichophyton (e.g. T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum) and Epidermophyton floccosum.

4.2 Posology And Method Of Administration

For cutaneous use.

Adults

Lamisil AT 1% Gel is applied once daily for all indications. Cleanse and dry the affected areas thoroughly before applying Lamisil AT 1% Gel. The gel should be rubbed in lightly to the affected skin and surrounding area. In the case of intertriginous infection (submammary, interdigital, intergluteal, inguinal) the application may be covered with a light gauze, especially at night.

Duration and frequency of treatment

Tinea corporis, tinea cruris	1 week once a day
Tinea pedis (interdigital type)	1 week once a day

Relief of clinical symptoms usually occurs within a few days. Irregular use or premature discontinuation of treatment carries the risk of recurrence. If there are no signs of improvement after two weeks, the diagnosis should be verified by a physician.

Use of Lamisil AT 1% Gel in the elderly

There is no evidence to suggest that elderly patients require different dosages or experience side effects different from those in younger patients.

Use of Lamisil AT 1% Gel in children

Not to be used in children under 16 years of age. Experience with Lamisil AT 1% Gel in children is limited and its use cannot therefore be recommended.

4.3 Contraindications

Known hypersensitivity to terbinafine or any of the excipients of the gel

(see 6.1 List of Excipients).

4.4 Special Warnings And Precautions For Use

Lamisil AT 1% Gel should be used with caution in patients with lesions where alcohol could be irritating, such as lesions which are markedly inflamed or on sensitive areas of the body such as the face.

Lamisil AT 1% Gel is for external use only. It may be irritating to the eyes. In case of accidental contact with the eyes, rinse eyes thoroughly with running water.

Lamisil AT 1% Gel should be kept out of the reach of children.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No drug interactions are known with Lamisil AT 1% Gel, however as a precaution it is recommended that other medicinal products are not applied on the treated areas.

4.6 Pregnancy And Lactation

Animal studies did not reveal any teratogenic or embryofoetotoxic potential of terbinafine. No cases of malformation in humans have been reported with terbinafine to date. However since clinical experience in pregnant women is very limited, Lamisil AT 1% Gel should only be used if clearly indicated during pregnancy.

Terbinafine is excreted in breast milk, and therefore mothers should not receive Lamisil AT 1% Gel whilst breast feeding. Infants should also not be allowed to come into contact with any treated skin, including the breast.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

Redness, itching or stinging may occur at the site of application, however treatment rarely has to be discontinued for this reason. These harmless symptoms must be distinguished from allergic reactions such as pruritus, rash, bullous eruptions and hives, which are rare but require discontinuation.

4.9 Overdose

No case of overdosage has been reported with Lamisil AT 1% Gel. Should, however, Lamisil AT 1% Gel be inadvertently ingested, adverse effects similar to those observed with an overdosage of Lamisil Tablets (e.g. headache, nausea, epigastric pain and dizziness) are to be expected.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antifungal for topical use (ATC Code D01A).

Terbinafine is an allylamine which has a broad spectrum of antifungal activity in fungal infections of the skin caused by dermatophytes such as Trichophyton (e.g. T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum canis and Epidermophyton floccosum. At low concentrations terbinafine is fungicidal against dermatophytes and moulds. The activity against yeasts is fungicidal (e.g. Pityosporum orbiculare or Malassezia furfur) or fungistatic, depending on the species.

Terbinafine interferes specifically with fungal sterol biosynthesis at an early step. This leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine acts by inhibition of squalene epoxidase in the fungal cell membrane. The enzyme squalene epoxidase is not linked to the cytochrome P450 system. Terbinafine does not influence the metabolism of hormones or other drugs.

Terbinafine has a long lasting action in athlete's foot. A clinical study of topical application of Lamisil AT 1% Gel in athlete's foot has shown a low percentage of patients with mycological evidence of relapse or reinfection after 7 weeks following cessation of treatment.

5.2 Pharmacokinetic Properties

Less than 5% of the dose is absorbed after topical application to humans; systemic exposure is thus very slight.

5.3 Preclinical Safety Data

In long term studies (up to 1 year) in rats and dogs, no marked toxic effects were seen in either species up to oral doses of about 100 mg/kg/day. At high oral doses, the liver and possible also the kidneys were identified as potential target organs.

In a two year carcinogenicity study in mice, no neoplastic or other abnormal findings attributable to treatment were made up to doses of 130 (males) and 156 (females) mg/kg/day. In a two year oral carcinogenicity study in rats at the highest dose level, 69 mg/kg/day, an increased incidence of liver tumours was observed in males. The changes, which may be associated with peroxisome proliferation, have been shown to be species specific since they were not seen in the carcinogenicity study in mice or in other studies in mice, dogs or monkeys.

During the studies of high dose oral terbinafine in monkeys, refractile irregularities were observed in the retina at the higher doses (non-toxic effect level was 50 mg/kg). These irregularities were associated with the presence of a terbinafine metabolite in ocular tissue and disappeared after drug discontinuation. They were not associated with histological changes.

A standard battery of in vitro and in vivo genotoxicity tests revealed no evidence of a mutagenic or clastogenic potential for the drug.

No adverse effects on fertility or other reproduction parameters were observed in studies in rats or rabbits.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Purified water

Ethanol

Isopropyl myristate

Polysorbate 20

Carbomer 974P

Sorbitan laurate

Benzyl alcohol

Sodium hydroxide

Butylated hydroxytoluene

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

Lamisil AT 1% Gel is available in aluminium tubes with sealing membrane, coated internally with an epoxyphenol resin lacquer. The tube is closed with a polypropylene screw cap, incorporating a point to pierce the aluminium sealing membrane before first use.

Available in tube sizes 5g, 7.5g, 15g and 30g.

6.6 Special Precautions For Disposal And Other Handling

See 4.2 Posology and Method of Administration and 4.4 Special Warnings and Precautions for Use.

Before first use, the sealing membrane of the tube must be pierced using the point incorporated into the screw cap.

7. Marketing Authorisation Holder

Novartis Consumer Health UK Limited

Wimblehurst Road

Horsham

West Sussex

RH12 5AB

Trading style: Novartis Consumer Health

8. Marketing Authorisation Number(S)

PL 00030/0191

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorization: 18 June 2003

Date of last renewal: 2 March 2009

10. Date Of Revision Of The Text

27 April 2009

Legal Category: P