GlaxoSmithKline (Ireland) Ltd

Zovirax 5% w/w Cream

Cream containing 5% w/w aciclovir.

Excipients: Contains propylene glycol 40% w/w and cetostearyl alcohol 6/75% w/w.

For a full list of excipients, see section 6.1.

Cream.

A smooth white to off-white cream.

Zovirax Cream is indicated for the treatment of Herpes simplex virus infections of the skin including initial and recurrent genital herpes and herpes labialis.

Zovirax Cream should be applied five times daily at approximately four hourly intervals omitting the night time application.

Zovirax Cream should be applied to the lesions or impending lesions as soon as possible preferably during the earliest stages (prodrome or erythema). Treatment can also be started during the later (papule or blister) stages.

Treatment should be continued for at least four days for herpes labialis and for five days for genital herpes. If healing has not occurred, treatment may be continued for up to ten days.

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

Zovirax Cream is not recommended for application to mucous membranes, such as in the mouth, eye or vagina as it may be irritant. 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. Such patients should be encouraged to consult a physician concerning the treatment of any infection.

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.

The use of Zovirax Cream should be considered only when the potential benefits outweigh 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.

Limited human data show that the drug does pass into breast milk following systemic administration. However, the dosage received by a nursing infant following maternal use of Zovirax 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 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 contents of a 10 gram tube of Zovirax Cream containing 500 mg of aciclovir were ingested orally. Oral doses of 800 mg aciclovir five times a day (4 grams per day) have been administered for 7 days without adverse effects.

Single intravenous doses of up to 80 mg/kg have been inadvertently administered without adverse effects. Aciclovir is dialysable.

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.

Pharmacology studies have shown only minimal systemic absorption of aciclovir following repeated topical administration of Zovirax Cream.

There is no information on the effect of aciclovir oral formulations or i.v. for infusion on human female fertility. In a study of 20 male patients with normal sperm count, oral aciclovir administered at doses of up to 1g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.

NON-CLINICAL INFORMATION

• Mutagenicity

The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir is unlikely to pose a genetic risk to man.

• Carcinogenicity

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

• Fertility

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at 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.

Cetostearyl alcohol

Liquid paraffin

Poloxamer 407

Propylene glycol

Purified water

Sodium laurilsulfate

White soft paraffin

Dimeticone 20

Glycerol Monostearate / Macrogol Stearate (Arlacel 165)

Not applicable

3 years

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

Zovirax Cream is stored in two sizes of the following container:

Aluminium tube – Collapsible lacquered aluminium tubes with 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 and 10g.

No special requirements

GlaxoSmithKline (Ireland) Ltd.

Stonemasons Way

Rathfarnham

Dublin 16

PA 1077/84/1

Date of first authorisation: 2 May 1984

Date of last renewal: 2 May 2009

October 2009