For definition of Groups, see Preamble Evaluation.
VOL.: 76 (2000) (p. 47)
Chem. Abstr. Name: 2-Amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one
Chem. Abstr. Name: 2-Amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one, sodium salt
5.1 Exposure data
Aciclovir is an acyclic nucleoside analogue which was first approved for use as an antiviral agent in 1982. It is used in the treatment of herpes simplex, varicella and herpes zoster viral infections. Oral and topical forms of aciclovir are very widely used for mucocutaneous infections. Intravenous preparations are widely used for some infections including encephalitis associated with herpes simplex viral infection and neonatal herpesvirus infection.
5.2 Human carcinogenicity data
The results of one prospective study and an extended observational follow-up indicated no increased risk for cancer among patients with recurrent herpes simplex infection given aciclovir orally, but, as the studies were not designed to investigate cancer, no conclusion can be drawn.
5.3 Animal carcinogenicity data
Aciclovir was tested for carcinogenicity in one experiment in mice and one experiment in rats by oral administration. The tumour incidence was not increased in either species.
5.4 Other relevant data
The pharmacokinetics of intravenously administered aciclovir in humans is stable over a wide dose range. The bioavailability of orally administered aciclovir is 15–30%. It is widely distributed, can cross the placenta and is, relative to many other antiviral drugs, slowly removed from plasma. More than half the administered drug is excreted unchanged, while the metabolite 9-carboxymethoxymethylguanine constitutes 8–14% of the dose. Urinary excretion can be markedly reduced in patients with impaired renal function. The pharmacokinetics of aciclovir in dogs is similar to that in humans, but the drug is removed more rapidly from the plasma of rats. Virtually all of the drug is recovered unchanged from dosed rats.
Adverse effects of aciclovir have been reported extremely rarely in people who have received oral or topical formulations. Higher doses are given intravenously in cases of serious illness, and most of the side-effects have been reported after such usage. The most common serious adverse effects are neurotoxicity and nephrotoxicity. Dogs and rats also show nephrotoxicity when treated at high doses.
Insufficient human data were available on the reproductive and prenatal effects of aciclovir. No developmental toxicity was reported in mice, rats or rabbits given doses over several days during gestation.
The available mutagenicity data indicate that aciclovir is primarily clastogenic at high concentrations, consistent with its action as a DNA chain terminator.
There is inadequate evidence in humans for the carcinogenicity of aciclovir.
There is inadequate evidence in experimental animals for the carcinogenicity of aciclovir.
Overall evaluationAciclovir is not classifiable as to its carcinogenicity to humans (Group 3). For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations