The upper layer of the epidermis on average showed a 48-fold higher concentration following topical application of Aciclovir ointment or cream 5% than after oral dosing, but the drug concentration in the basal epidermis – the site of herpes virus infection – was 2 to 3 times lower following topical application than after oral dosing.

On the basis of continuous absorption the concentration increased as a function of time (higher drug concentrations being found 48 hours post-topical dose than 24 hours post-topical dose).

Thus short dosing intervals appear rational for the special treatment of herpes simplex virus (HSV) infections.

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
For 24 days, PEG-based Aciclovir Cream 5% or 10% was applied to the shaved (intact and grazed) skin of guinea-pigs. The treated area corresponded to 10% of the body surface. There were neither systemic nor local toxic symptoms. This is also confirmed by histological studies and autopsy. According to the test carried out by Draize, who eva luated the allergic sensitising potential of a substance, there were no pathogenic findings.

Studies carried out in swine showed that 5% Aciclovir cream in a PEG vehicle caused an only minimal (quantitative) delay in epidermal wound healing.

Rabbits had 1%, 3% or 6% Aciclovir cream in a white petrolatum vehicle introduced directly into both eyes 5 times daily at 90-minute intervals for 3 weeks. Neither autopsy nor inspection nor histological examination revealed any pathological changes in the rabbit eyes.

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
Stearoyl macrogoglycerides

Dimeticone

Cetyl alcohol

Liquid paraffin

White soft paraffin

Propylene glycol

Purified water

6.2 Incompatibilities
Not applicable.

6.3 Shelf life
3 years (unopened)

6 weeks (open)

6.4 Special precautions for storage
Do not store above 25°C. Do not refrigerate.

6.5 Nature and contents of container
Aluminium tube with polyethylene screw cap.

Pack size: 2 g

6.6 Special precautions for disposal and other handling
Not applicable

7. Marketing authorisation holder
Pinewood Laboratories Limited

Ballymacarbry

Clonmel

Co. Tipperary

Ireland

8. Marketing authorisation number(s)
PL 04917/0056

9. Date of first authorisation/renewal of the authorisation
31 December 2002 / 30 January 2009

10. Date of revision of the text
07/07/2014