Fenistil^® Cold Sore Cream

Eeach gram of the cream contains:

Active substance: 10 mg penciclovir

Excipients: cetostearyl alcohol, propylene glycol

For a full list of excipients, see section 6.1.

Cream

Smooth white cream of homogeneous appearence

Fenistil Cold Sore Cream is indicated for the treatment of herpes simplex virus infections of the lips and face (herpes labialis) in adults and children over 12 years of age.

Immunocompromised patients: Fenistil Cold Sore Cream.is not recommended for use in immunocompromised patients; such patients should consult a physician concerning the treatment of any infection.

Adults (including the elderly) and children over 12 years of age:

Fenistil Cold Sore Cream should be applied at approximately two hourly intervals during waking hours, (approximately 8 times a day). Treatment should be continued for 4 days. If the condition gets worse or does not improve after 4 days treatment, seek medical advice.

Treatment should be started as early as possible after the first sign of an infection.

Children (under 12 years):

No work has been carried out in children below 12 years of age.

Known hypersensitivity to penciclovir, famciclovir or the other constituents of the formulation, eg. propylene glycol.

The cream should only be used on cold sores on the lips and around the mouth. It is not recommended for application to the mucous membranes, such as in the mouth or eye, or on the genitals. It must not be used in ocular or genital herpes. Particular care should be taken to avoid contact with the eyes.

Patients with particularly severe cold sores should be encouraged to seek medical advice.

Patients should be advised to avoid transmitting the virus, particularly when active lesions are present.

Immunocompromised patients (eg AIDs patients or bone marrow transplant recipients) should be encouraged to consult a physician in case oral therapy is indicated.

The cream contains cetostearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis). It also contains propylene glycol, which may cause skin irritation.

Clinical trial experience has not identified any interactions resulting from concomitant administration of topical or systemic drugs with Fenistil Cold Sore Cream.

There is unlikely to be any cause for concern regarding adverse effects when the cream is used in pregnant and/or lactating women as systemic absorption of penciclovir following topical administration of Fenistil Cold Sore Cream has been shown to be minimal (see Section 5.2).

Animal studies have not shown any embryotoxic or teratogenic effects with penciclovir given intravenously (at doses greater than 1200 times those recommended for clinical use via topical application), nor were there any effects on male and female fertility and general reproductive performance (at doses greater than 1600 times those recommended for clinical use via topical application). Studies in rats show that penciclovir is excreted in the breast milk of lactating females given oral famciclovir (famciclovir; the oral form of penciclovir, is converted in vivo to penciclovir). There is no information on excretion of penciclovir in human milk.

Since the safety of penciclovir in human pregnancy has not been established, Fenistil Cold Sore Cream should only be used during pregnancy or in nursing mothers on the advice of a doctor, if the potential benefits are considered to outweigh the potential risks associated with treatment.

Adverse effects on the ability to drive or operate machinery have not been observed.

Fenistil Cold Sore Cream has been well-tolerated in human studies. Clinical trial experience has shown that there was no difference between Fenistil Cold Sore Cream and placebo in the rate or type of adverse reactions reported. In particular, application site reactions (eg transient burning, stinging, numbness) occurred in less than 3% of patients in each group in the pivotal clinical trials.

Post-marketing surveillance from penciclovir cream has revealed isolated cases of hypersensistivity reactions, such as allergic dermatitis, rash, urticaria, pruritis and oedema.

No cases of photosensitivity were reported in the pivotal clinical trials.

No untoward effects would be expected even if the entire contents of a container of Fenistil Cold Sore Cream were ingested orally; penciclovir is poorly absorbed following oral administration. However, some irritation in the mouth could occur. No specific treatment is necessary if accidental oral ingestion occurs.

Penciclovir has demonstrable in vivo and in vitro activity against herpes simplex viruses (types 1 and 2) and varicella zoster virus. In virus-infected cells penciclovir is rapidly and efficiently converted into a triphosphate (mediated via virus-induced thymidine kinase). Penciclovir triphosphate persists in infected cells for more than 12 hours where it inhibits replication of viral DNA and has a half-life of 9, 10 and 20 hours in cells infected with varicella zoster virus, herpes simplex virus type 1 and herpes simplex virus type 2 respectively. In uninfected cells treated with penciclovir, concentrations of penciclovir triphosphate are only barely detectable. Accordingly, uninfected cells are unlikely to be affected by therapeutic concentrations of penciclovir.

In clinical studies, Fenistil treated patients healed 30% faster than placebo (up to one day earlier), pain resolution was 25-30% faster (median improvement of up to one day) and infectivity resolved up to 40% faster (one day earlier) than placebo.

Following application of Fenistil Cold Sore Cream in a human volunteer study at a daily dose of 180mg penciclovir (approximately 67 times the proposed daily clinical dose), to occluded and abraded skin for 4 days, penciclovir was not quantifiable in plasma and urine.

General toxicology

Topical application of 5% Fenistil Cold Sore Cream for 4 weeks to rats and rabbits was well tolerated. There was no evidence of contact sensitisation in guinea pigs.

A full programme of studies has been completed using intravenous penciclovir. These studies did not raise any safety concerns regarding topical use of Fenistil Cold Sore Cream. There is a minimal systemic absorption of penciclovir following topical administration.

The results of a wide range of mutagenicity studies in vitro and in vivo indicates that penciclovir does not pose a genotoxic risk to man.

White soft paraffin

Liquid paraffin

Cetostearyl alcohol

Propylene glycol

Cetomacrogol 1000

Purified water

Not applicable.

2g aluminium tubes - 3 years.

Store at temperatures not exceeding 30°C.

Do not freeze.

2g aluminium tube.

No special requirements.

Novartis Consumer Health (UK) Limited

Wimblehurst Road

Horsham

West Sussex RH12 5AB

UK

Trading as: Novartis Consumer Health

PL 00030/0215

23^rd August 2006

5 November 2009

Legal category: P