8.1 Pregnancy:
Risk Summary
A prospective epidemiologic registry of acyclovir use from 1984 to 1999 indicated that the occurrence rate of birth defects inwomen exposed to systemically administered acyclovir during the first trimester of pregnancy (period of organogenesis)approximated that found in the general population. Likewise, oral and subcutaneous administration of acyclovir to pregnant mice,rats, and rabbits during organogenesis did not produce teratogenicity at clinically relevant doses [see Animal Data].
Data
Human Data
A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999.
There were 749 pregnancies followed in women exposed to systemically administered acyclovir during the first trimester ofpregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximates that found in the general population.
However, the small size of the registry is insufficient to eva luate the risk for less common defects, or to permit reliable ordefinitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses. The human maternalplasma level of acyclovir following ocular administration is unknown.
Animal Data
In published animal reproduction studies, acyclovir was not maternally toxic and did not produce teratogenicity in the mouse atoral doses up to 450 mg/kg/day (1100 times the maximum recommended human ophthalmic dose [RHOD] on a mg/m2 basis,assuming 100% absorption), or in the rat and rabbit at subcutaneous doses up to 50 mg/kg/day (approximately 250 and 500times the RHOD, respectively) when administered throughout the period of organogenesis.
Administration of acyclovir from postnatal days 3 to 21 did not produce adverse effects in neonatal rats at subcutaneous dosesless than or equal to 20 mg/kg/day (100 times the RHOD).
8.3 Lactation:
Risk Summary
Acyclovir concentrations have been documented in breast milk following oral administration of acyclovir There is no informationregarding the presence of acyclovir in human milk following ocular administration, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for acyclovir, and any potential adverse effects on the breast-fed child from acyclovir or from theunderlying maternal condition.
8.4 Pediatric Use: Safety and efficacy of Acyclovir ophthalmic ointment in pediatric patients below the age of two years has notbeen established.
8.5 Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adultpatients..
10 OVERDOSAGE
Overdosage of topical application of acyclovir 3% is unlikely because of minimal absorption.
11 DESCRIPTION
Acyclovir is a synthetic herpes simplex virus nucleoside analog DNA polymerase inhibitor. The drug substance is a whitecrystalline powder with the molecular formula of C8H11N5O3 and a molecular weight of 225.2. The maximum solubility in water at25°C is 1.41 mg/mL. The pka’s of acyclovir are 2.52 and 9.35.
The chemical name of acyclovir is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]6H-purin-6-one, it has the following chemicalstructure:
AVACLYR is a sterile ointment for topical administration in eyes. Each gram of ointment contains 30 mg of acyclovir in a whitepetrolatum base.
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