Lamisil^® Once^TM 1% cutaneous solution

Each gram contains 10 mg terbinafine (as hydrochloride).

For excipients, see section 6.1.

Cutaneous solution.

Clear to slightly opaque viscous solution.

Treatment for tinea pedis (athlete's foot).

Adults 18 years of age and over: single administration.

Lamisil Once should be applied once on both feet, even if lesions are visible on one foot only. This ensures elimination of the fungi (dermatophytes) that might be found in areas of the foot where no lesions are visible.

Patients should wash and dry both feet and hands before applying the product. They should treat one foot, then the other.

Starting between the toes, patients should apply a thin layer evenly between and all around the toes, as well as cover the sole and sides of the foot for up to 1.5 cm. The product should be applied in the same way to the other foot, even if the skin looks healthy. The product should be left to dry to a film for 1-2 minutes. Patients should then wash their hands. Lamisil Once should not be massaged into skin.

For the best results, the treated area should not be washed for 24 hours after application. It is therefore recommended to apply Lamisil Once after a shower or bath and wait until the same time the following day before washing the feet again.

Patients should use the quantity they need to cover both feet as instructed above. Any unused medication is to be discarded.

Relief of clinical symptoms usually occurs within a few days. If there are no signs of improvement after one week, patients should see a doctor. There are no data on repeated treatment with Lamisil Once. Therefore a second treatment cannot be recommended within a particular episode of athlete's foot.

Children:

Lamisil Once has not been studied in the paediatric population. Its use is therefore not recommended in patients below 18 years of age.

The elderly:

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

Hypersensitivity to terbinafine or any of the excipients (see 6.1. List of excipients).

Lamisil Once is not recommended to treat hyperkeratotic chronic plantar tinea pedis (moccasin type).

Lamisil Once is for external use only. It should not be used on the face; it may be irritating to the eyes. In case of accidental contact with the eyes, rinse eyes thoroughly with running water. Do not swallow.

In the unlikely event of allergic reaction, the film should be removed with an organic solvent such as denatured alcohol and the feet washed with warm soapy water.

Contains alcohol; keep away from naked flames

No drug interactions are known with use of topical Lamisil formulations.

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

Terbinafine is excreted in breast milk, and therefore mothers should not receive Lamisil Once whilst breast-feeding.

Cutaneous application of Lamisil Once does not affect the ability to drive and use machines.

Undesirable effects include mild and transient reactions at the site of application. In very rare instances, allergic reactions may occur.

Skin and subcutaneous tissue disorders:

Very rare (<1/10,000, including isolated reports): allergic reactions such as rash, pruritus, dermatitis bullous and urticaria.

General disorders and administration site conditions

Uncommon (>1/1,000, <1/100): application site reactions such as skin dryness, skin irritation or burning sensation.

Overdose is very unlikely to happen since the product is for single dose, cutaneous use, and the tube only contains the necessary quantity for one application. Accidental ingestion of one 4 g tube of product which contains 40 mg terbinafine is much lower than one 250 mg Lamisil tablet (oral unit dose). Should several tubes be ingested however, adverse effects similar to those observed with an overdose of Lamisil tablets (e.g. headache, nausea, epigastric pain and dizziness) are to be expected.

Pharmacotherapeutic group: Antifungal for topical use (ATC code D01 A E15)

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. Pityrosporum 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.

Studies in patients have shown that a single dose application of Lamisil Once 1 % cutaneous solution on both feet demonstrated efficacy in patients with tinea pedis (athlete's foot) presenting lesions between the toes, and extending to adjacent skin areas of the sides and soles of the feet. The rate of relapse/reinfection at 3 months after treatment was low: 1 person out of 8 (12.5%).

Once applied to the skin, Lamisil Once 1 % cutaneous solution forms a film on the skin. Terbinafine in the film stays on the skin for up to 72 hours. The film quickly delivers terbinafine to the stratum corneum: at 60 minutes after application, 16 to 18% of the applied dose will be present in the stratum corneum. Delivery progressively continues and terbinafine persists in the stratum corneum for up to 13 days, at levels which are in excess of the in vitro Minimum Inhibitory Concentration for terbinafine against dermatophytes.

Systemic bioavailability is very low. An application of Lamisil Once 1 % cutaneous solution on the back, on an area of 3 times the area of both feet, resulted in exposure to terbinafine of less than 0.5% of the exposure following oral administration of a 250 mg tablet.

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 a day. At high oral doses, the liver and possibly also the kidneys were identified as potential target organs.

In a two-year oral 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 a day. In a two-year oral carcinogenicity study in rats at the highest dose level, 69 mg/kg a 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 no associated 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.

Repeated dermal administration of Lamisil Once 1 % cutaneous solution in rats and minipigs produces plasma terbinafine levels which are at least 50-100 times lower than the no-adverse-effect-levels established in terbinafine animal toxicity studies, so use of the product is not expected to produce any systemic adverse effect. Lamisil Once 1 % cutaneous solution was well tolerated in a variety of tolerability studies and did not cause sensitisation.

Acrylates/octylacrylamide copolymer;

hydroxypropylcellulose;

medium chain triglycerides;

ethanol.

Not applicable.

3 years.

Store in the original package. There is no special temperature precaution for storage.

4 g aluminium laminated tube (polyethylene-aluminium-polyethylene) with a polyethylene screw cap.

No special requirements.

Novartis Consumer Health, Horsham, RH12 5AB, UK

PL 00030/0213

4 November 2005

23 November 2005

Legal category: GSL