Breast-feeding:

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.

Fertility:

There is no information on the effect of aciclovir 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.

See Clinical Studies in section 5.2

4.7 Effects on ability to drive and use machines
Not applicable

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.

Immune system disorders:

Very rare

• Immediate hypersensitivity reactions including angioedema and urticaria.

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.

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 contents of a 10 gram tube of Zovirax Cream containing 500 mg of aciclovir were ingested orally. However the accidental, repeated overdose of oral aciclovir, over several days has resulted in gastrointestinal effects (nausea and vomiting) and neurological effects (headache and confusion). Aciclovir is dialysable by haemodialysis.

5. Pharmacological properties
5.1 Pharmacodynamic properties
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

In two large, double blind, randomised clinical studies involving 1,385 subjects treated over 4 days for recurrent herpes labialis, Zovirax Cream 5% was compared to vehicle cream. In these studies, time from start of treatment to healing was 4.6 days using Zovirax Cream and 5.0 days using vehicle cream (p<0.001). Duration of pain was 3.0 d