GlaxoSmithKline Consumer Healthcare (Ireland) Ltd

Zovirax Cold Sore 5% w/w Cream

5% w/w aciclovir

Excipients: contains 40 %w/w propylene glycol (E 1520) and 6.75 % w/w Cetostearyl alcohol.

For a full list of excipients, see section 6.1

Cream

A smooth white to off-white cream.

Zovirax Cold Sore Cream is indicated for the treatment of herpes simplex virus infections of the skin, lips and face (recurrent herpes labialis).

Adults:

Zovirax Cold Sore Cream should be applied five times daily at approximately four hourly intervals omitting the night time application. Treatment should be continued for at least 4 days. If healing has not occurred, treatment may be continued for up to 10 days. If lesions are still present after 10 days, users should be advised to consult a doctor.

Zovirax Cold Sore Cream should be applied as soon as possible, preferably during the earliest stages (prodome or erythema). Treatment can also be started during the later (papule or blister) stages.

Children:

Children should use the adult dose.

Zovirax Cold Sore Cream is contra-indicated in patients known to be hypersensitive to aciclovir, valaciclovir, propylene glycol or any of the excipients of Zovirax Cold Sore Cream.

Zovirax Cold Sore Cream should only be used on cold sores on the lips and face. It is not recommended for application to mucous membranes, such as in the mouth or eye. Particular care should be taken to avoid contact with the eye.

In severely immunocompromised patients (e.g. AIDS patients or bone marrow transplant recipients) oral dosing should be considered.

People with particular severe recurrent herpes labialis should be encouraged to seek medical advice.

Cetostearyl alcohol may cause local skin reactions (e.g. contact dermatitis).

Propylene glycol may cause skin irritation.

No clinically significant interactions have been identified.

A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of Zovirax. The registry findings have not shown an increase in the number of birth defects amongst Zovirax exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause. Systemic exposure to aciclovir from topical application of Zovirax Cold Sore Cream is very low.

Experience in humans is limited, so the use of Zovirax Cold Sore Cream should be considered only when the potential benefit outweighs the possibility of unknown risks.

Systemic administration of aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice.

In a non-standard test in rats, foetal abnormalities were observed but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.

Following oral administration of 200mg aciclovir five times a day, the drug has been detected in human breast milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma concentrations. These concentrations would potentially expose nursing infants to aciclovir dosages of up to 0.3mg/kg/day. The dosage received by a nursing infant following maternal use of Zovirax Cold Sore Cream would be insignificant.

Not applicable.

The following convention has been used for the classification of undesirable effects in terms of frequency: Very common 1/10, common 1/100 and < 1/10, uncommon 1/1000 and < 1/100, rare 1/10,000 and < 1/1000, very rare < 1/10,000.

Skin and subcutaneous tissue disorders

Uncommon

• Transient burning or stinging following application of Zovirax Cold Sore Cream

• Mild drying or flaking of the skin

• Itching

Rare

• Erythema

• Contact dermatitis following application. Where sensitivity tests have been conducted, the reactive substances have most often been shown to be components of the cream rather than aciclovir.

Immune system disorders

Very rare

• Immediate hypersensitivity reactions including angioedema.

No untoward effects would be expected if the entire 2g contents of Zovirax Cold Sore Cream containing 100 mg of aciclovir were ingested orally.

Aciclovir is an antiviral agent which is highly active in vitro against Herpes simplex virus (HSV) types I and II and Varicella zoster virus. Toxicity to mammalian host cells is low.

Aciclovir is phosphorylated after entry into herpes infected cells to the active compound aciclovir triphosphate. The first step in this process is dependent on the presence of the HSV-coded thymidine kinase.

Aciclovir triphosphate acts as an inhibitor of, and substrate for the herpes specified DNA polymerase, preventing further viral DNA synthesis without affecting normal cellular processes.

Zovirax Cold Sore Cream significantly reduced episode healing time (p<0.02) and time to pain resolution (p<0.03) compared with placebo cream in two large, double-blind, randomised clinical studies involving 1,385 subjects with recurrent herpes labialis. Overall approximately 60% of patients started treatment at an earlier lesion stage (prodome or erythema) and 40% at a late lesion stage (papule or blister).

Limited pharmacology studies have shown only minimal systemic absorption of aciclovir following repeated topical administration of Zovirax Cold Sore Cream.

The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir does not pose a genetic risk to man.

Aciclovir was not found to be carcinogenic in long-term studies in the rat and the mouse.

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at systemic doses of aciclovir greatly in excess of those employed therapeutically. Two-generation studies in mice did not reveal any effect of orally administered aciclovir on fertility.

There is no experience on the effect of Zovirax Cold Sore Cream on human female fertility. In patients with normal sperm count, chronically administered oral aciclovir has been shown to have no clinically significant effect on sperm count, motility or morphology.

Cetostearyl alcohol

Liquid paraffin

Poloxamer 407

Propylene glycol (E 1520)

Purified water

Sodium laurilsulfate

White soft paraffin

Dimeticone

Glycerol monostearate

Macrogol stearate

None applicable.

3 years in aluminium tubes.

2 years in pump container.

Do not store above 25°C. Do not refrigerate.

Zovirax Cold Sore Cream is stored in two types of containers:

Aluminium tube - Collapsable lacquered aluminium tubes with polyethylene plastic screw caps. The tubes contain a latex end-seal at the crimped end and a membrane seal at the nozzle end. A spike is incorporated into the structure of the cap.

Pack size: 2g.

Pump assembly - Polypropylene container with pump assembly and polypropylene cap.

Pack size: 2g.

Not all pack sizes may be marketed.

No special requirements.

GlaxoSmithKline Consumer Healthcare (Ireland) Ltd.,

Stonemasons Way,

Rathfarnham,

Dublin 16

PA 678/90/2

Date of first authorisation: 16 July 1993

Date of last renewal: 16 July 2008

April 2010