ZOVIRAX COLD SORE CREAM - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Zovirax Cold Sore Cream

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

100mg Aciclovir equivalent to 5% w/w

Excipients with known effect: 400 mg propylene glycol and 7.5 mg sodium laurilsulfate / gram cream.

Cream

4.1 Therapeutic indications

Zovirax Cold Sore Cream is indicated in adults and children for the treatment of

Herpes simplex virus infections of the lips and face (recurrent herpes labialis).

Immunocompromised Patients

Zovirax Cold Sore Cream is not recommended for use in immunocompromised patients. Such patients must be advised to consult a physician concerning the treatment of any infection.

4.2 Posology and method of administration

Route of administration – Topical

Adults and children

Zovirax Cold Sore Cream should be applied five times daily at approximately four hourly intervals, omitting the night time application. Zovirax Cold Sore 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 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. Users should wash their hands before and after applying the cream, and avoid unnecessary rubbing of the lesions or touching them with a towel, to avoid aggravating or transferring the infection.

Use in the Elderly

No special comment.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Zovirax Cold Sore cream should only be used on cold sores on the mouth and face. It is not recommended for application to mucous membranes, such as in the mouth or eye and must not be used to treat genital herpes.

Particular care should be taken to avoid contact with eye. People with particularly severe recurrent herpes labialis should be encouraged to seek medical advice.

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

Zovirax cold sore cream is not recommended for use by people who know that they are immunocompromised. Such individuals should be encouraged to consult a physician concerning the treatment of any infection.

Zovirax Cold Sore Cream contains 200 mg propylene glycol in each daily dose which is equivalent to 400 mg/g. Propylene glycol can cause skin irritations.

Zovirax Cold Sore Cream contains 3.75 mg sodium laurilsulfate in each daily dose which is equivalent to 7.5 mg/g. Sodium laurilsulfate may cause local skin reactions (such as stinging or burning sensation) or increase skin reactions caused by other products when applied on the same area.

The excipient cetyl alcohol can cause local skin reactions (e.g. contact dermatitis).

Ocular herpes

Zovirax Cold Sore Cream must not be used for treatment of ocular herpes infections.

Genital herpes

Zovirax Cold Sore Cream must not be used for treatment of genital herpes.

4.5 Interaction with other medicinal products and other forms of interaction No clinically significant interactions have been identified.

4.6 Fertility, Pregnancy and lactation

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

A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of Zovirax. The birth defects described amongst Zovirax exposed subjects have not shown any uniqueness or consistent pattern to suggest a common cause.

The use of Zovirax Cold Sore Cream should be considered only when the potential benefits outweigh the possibility of unknown risks however the systemic exposure to aciclovir from topical application of aciclovir cream is very low.

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 Cold Sore Cream would be expected to be insignificant.

Fertility

There is no information on the effect of aciclovir on human female fertility.

See Clinical Studies in section 5.2.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

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 base rather than aciclovir.

Immune system disorders

Very rare

– Immediate hypersensitivity reactions including angioedema and urticaria.

4.9 Overdose

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

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: D06 BB 03

Aciclovir is an antiviral agent which is highly active in vitro against herpes simplex virus (HSV) types 1 and 2. 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.

In two multicentre, double blind, randomised clinical studies involving 1,385 subjects treated over 4 days for recurrent herpes labialis, Zovirax Cold Sore Cream 5% was compared to vehicle cream. Based on the pooled dataset from the two studies the mean time from clinician-assessed start of treatment to healing (episode duration) was 4.6 days using Zovirax Cold Sore Cream and 5.0 days using vehicle cream (p<0.001). The median clinician-assessed episode duration was 4.0 days using aciclovir cream (25%-ile=3.0 days, 75%-ile=6.0 days) and 4.3 days using vehicle cream (25%-ile=3.1 days, 75%-ile=6.6 days), with a corresponding hazard ratio of 1.22 (p<0.001).

The median duration of subject-assessed pain was 2.9 days using aciclovir cream and 3.0 days using vehicle cream, with a corresponding hazard ratio of 1.21 (p<0.001).

Overall, approximately 60% of subjects started treatment at an early lesion stage (prodrome or erythema) and 40% at a late stage (papule or vesicle).

5.2 Pharmacokinetic properties

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

Clinical Studies

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.

5.3 Preclinical safety data

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 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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Poloxamer 407

Cetostearyl alcohol*

Sodium laurilsulfate*

White soft paraffin

Arlacel 165 (Macrogol stearate 100 and Glycerol monostearate)

Liquid paraffin

Dimeticone

Propylene glycol

Purified water

* Alternatively emulsifying wax

6.2

None known.

6.3

36 months in aluminium tubes.

24 months in pump container.

6.4 Special precautions for storage

Store below 25°C, do not refrigerate.

6.5 Nature and contents of container

Zovirax Cold Sore Cream is stored in two types of 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

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

Pack size: 2G

6.6 Special precautions for disposal

For external use only.