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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard.
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
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 large, 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. In these studies, time from start of treatment to healing was 4.6 days using Zovirax Cold Sore Cream and 5.0 days using vehicle cream (p<0.001). Duration of pain was 3.0 days after start of treatment in the Zovirax Cold Sore Cream group and 3.4 days in the vehicle group (p=0.002). Overall, ap