Acyclovir ointment is intended for cutaneous use only and should not be used in the eye.

General

The recommended dosage, frequency of applications, and length of treatment should not be exceeded (see DOSAGE AND ADMINISTRATION.) There exist no data which demonstrate that the use of acyclovir ointment 5% will either prevent transmission of infection to other persons or prevent recurrent infections when applied in the absence of signs and symptoms. Acyclovir ointment 5% should not be used for the prevention of recurrent HSV infections. Although clinically significant viral resistance associated with the use of acyclovir ointment 5% has not been observed, this possibility exists.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Acyclovir was tested in lifetime bioassays in rats and mice at single daily doses of 50, 150 and 450 mg/kg/day given by gavage. These studies showed no statistically significant difference in the incidence of benign and malignant tumors produced in drug-treated as compared to control animals, nor did acyclovir induce the occurrence of tumors earlier in drug-treated animals as compared to control. In two in vitro cell transformation assays, used to provide preliminary assessment of potential oncogenicity in advance of these more definitive lifetime bioassays in rodents, conflicting results were obtained. Acyclovir was positive at the highest dose used in one system and the resulting morphologically transformed cells formed tumors when inoculated into immunosuppressed, syngeneic, weanling mice. Acyclovir was negative in another transformation system.

No chromosome damage was observed at maximum tolerated parenteral doses of 100 mg/kg acyclovir in rats or Chinese hamsters; higher doses of 500 and 1000 mg/kg were clastogenic in Chinese hamsters. In addition, no activity was found in a dominant lethal study in mice. In 9 of 11 microbial and mammalian cell assays, no evidence of mutagenicity was observed. In two mammalian cell assays (human lymphocytes and L5178Y mouse lymphoma cells in vitro), positive response for mutagenicity and chromosomal damage occurred, but only at concentrations at least 1000 times the plasma levels achieved in humans following topical application.

Acyclovir does not impair fertility or reproduction in mice at oral doses up to 450 mg/kg/day or in rats at subcutaneous doses up to 25 mg/kg/day. In rabbits given a high dose of acyclovir (50 mg/kg/day SC), there was a statistically significant decrease in implantation efficiency.

Pregnancy

Teratogenic Effects: Pregnancy Category C: Acyclovir was not teratogenic in the mouse (450 mg/kg/day, P.O.), rabbit (50 mg/kg/day, S.C. and I.V.), or in standard tests in the rat (50 mg/kg/day S.C.). In a non-standard test in rats, fetal abnormalities, such as head and tail anomalies, were observed following subcutaneous administration of acyclovir at very high doses associated with toxicity to the maternal rat. The clinical relevance of these findings is uncertain. There are no adequate and well-controlled studies in pregnant women. Acyclovir should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether topically applied acyclovir is excreted in breast milk. After oral administration of acyclovir, concentrations have been documented in breast milk in two women and ranged from 0.6 to 4.1 times the corresponding plasma levels. Caution should be exercised when acyclovir ointment is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children have not been established.

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