Vectavir^® Cold Sore Cream

Each 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 appearance.

Vectavir Cold Sore Cream is indicated for the treatment of cold sores (herpes labialis) .

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

Vectavir Cold Sore Cream should be applied at approximately two hourly intervals during waking hours. Vectavir Cold Sore Cream may be applied with a clean finger or with a single-use applicator (for packages which contain applicators), in the amount required for the size of the affected area of skin. Treatment should be continued for 4 days.

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 any of the excipients 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 mucous membranes (e.g. in the eyes, mouth, or nose or on the genitals). Particular care should be taken to avoid application in or near the eyes.

Severely 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 Vectavir 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 Vectavir Cold Sore Cream has been shown to be minimal (see Section 5.2).

There is no information on excretion of penciclovir in human milk.

Since the safety of penciclovir in human pregnancy has not been established, Vectavir 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.

Vectavir Cold Sore Cream has been well-tolerated in human studies. Clinical trial experience has shown that there was no difference between Vectavir Cold Sore Cream and placebo in the rate or type of adverse reactions reported. The most common events are application site adverse events.

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (1/10); common (1/100 to < 1/10); uncommon (1/1,000 to <1/100); rare ( 1/10,000 to < 1/1,000); very rare (<1/10,000); unknown (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

General disorders and administration site condition

Common: application site reactions (including skin burning sensation, pain of skin, hypoaesthesia)

Post-marketing surveillance has revealed the following adverse events (all reactions were either localised or generalised). Adverse events from post-marketing experience are difficult to calculate a frequency for and therefore the events are listed as unknown frequency.

Immune system disorders

hypersensitivity, urticaria

Skin and subcutaneous disorders

dermatitis allergic (including rash, pruritus, blisters and oedema).

No untoward effects would be expected even if the entire contents of a container of Vectavir 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, Vectavir Cold Sore Cream 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 Vectavir 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% Vectavir 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 Vectavir Cold Sore Cream. There is a minimal systemic absorption of penciclovir following topical administration.

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).

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 (see section 4.4 'Special warnings and precautions for use')

Propylene glycol (see section 4.4 'Special warnings and precautions for use')

Cetomacrogol 1000

Purified water

Not applicable.

2g and 5g aluminium tubes - 3 years.

2g plastic airless pump dispenser - 2 years.

Store at temperatures not exceeding 30°C.

Do not freeze.

2g and 5g aluminium tube. May be supplied with 20 single-use Low Density Polyethylene (LDPE) applicators.

2g plastic airless pump dispenser.

Not all pack sizes may be marketed.

No special requirements.

Novartis Consumer Health (UK) Limited

Wimblehurst Road

Horsham

West Sussex RH12 5AB

UK

Trading as: Novartis Consumer Health

PL 00030/0210

Date of first authorisation: 2 June 2003

Date of last renewal: 16 April 2006

07 April 2011

POM