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 days after start of treatment in the Zovirax Cream group and 3.4 days in the vehicle group (p=0.002). Overall, approximately 60% of patients started treatment at an early lesion stage (prodrome or erythema) and 40% at a late stage (papule or blister). The results were similar in both groups of patients.
Pharmacology studies have shown only minimal systemic absorption of aciclovir following repeated topical administration of Zovirax Cream.
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 only at 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.
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.