Fertility

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses greatly in excess of those employed therapeutically. Two generation studies in mice did not reveal any effect of orally administered Aciclovir on fertility. See Clinical Studies in section 5.2.

There is no experience of the effect of Aciclovir tablets on human female fertility. Aciclovir tablets have been shown to have no definite effect upon sperm count, morphology or motility in man.

Lactation

Following oral administration of 200 mg Aciclovir five times a day, Aciclovir has been detected in breast milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma levels. These levels would potentially expose breast fed infants to Aciclovir doses of up to 0.3 mg/kg/day.

4.7 Effects on ability to drive and use machines
The medicinal product has no influence on the ability to drive or operate machinery.

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

Common

- Mild drying or flaking of the skin

Uncommon

- 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.

After application of the cream, transient burning or stinging of the treated skin areas may occur.

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
Overdose is unlikely to occur, if the cream is applied locally as indicated. There are no reports concerning an overdose of Aciclovir cream.

No unwanted effects would be expected if the entire contents of a 2.0 g tube of the cream were ingested. Doses of 800 mg five times daily (4 g per day), have been administered without adverse effects. Single intravenous doses of up to 80 mg/kg have been inadvertently administered without adverse effects. Aciclovir is dialyzable.

5. Pharmacological properties
5.1 Pharmacodynamic properties
Aciclovir is a pharmacologically inactive substance. After penetration into cells which are infected with herpes simplex virus types I and II (HSV I & HSV II) or varicella-zoster virus (VSV), Aciclovir is converted into a virostatic agent. The conversion of Aciclovir is catalysed by viral HSV- or VZV- thymidine kinase. Human thymidine kinase does not use Aciclovir effectively as a substrate; hence the toxicity to mammalian host cells is low.

In the infected cell, Aciclovir is phosphorylated by viral thymidine kinase to Aciclovir monophosphate, which is further converted by cellular enzymes to Aciclovir triphosphate. Aciclovir triphosphate has a greater affinity f