Fetal Risk Summary
Famciclovir is a prodrug administered orally for the treatment of infections involving herpes simplex virus types 1 and 2, or varicella zoster virus. After administration, the drug undergoes rapid biotransformation to penciclovir, the active antiviral compound. Specific indications are the treatment of recurrent episodes of genital herpes and the management of acute herpes zoster (shingles) (1).
Carcinogenic, but not embryotoxic or teratogenic, effects were observed in animal studies with famciclovir (1). A significant increase in the incidence of mammary adenocarcinoma was seen in female rats administered famciclovir 600 mg/kg/day, 1.59.0 times the levels achieved with the recommended human doses, based on area under the plasma concentration curve (AUC) comparisons for penciclovir. At this dose in female rats and at doses up to 2.4 times the human dose (AUC comparison) in male mice, marginal increases in the incidence of subcutaneous tissue fibrosarcomas and squamous cell carcinomas of the skin were observed. The tumors, however, were not observed in male rats and female mice. The reasons for these interesting gender differences are apparently unknown.
Both famciclovir and the active metabolite, penciclovir, were tested for teratogenicity in pregnant rats and rabbits (1). Based on the penciclovir levels achieved with the recommended human doses (AUC comparison), oral doses of famciclovir up to 21.6 times (rats) and 10.8 times (rabbits) those concentrations had no effect on embryo and fetal development. Intravenous famciclovir also had no effect on embryo and fetal development in either the rat or the rabbit at doses up to 12 and 9 times, respectively, the human dose, based on body surface area (BSA) comparisons. A similar lack of toxicity was observed with intravenous penciclovir at doses in pregnant rats and rabbits up to 2.6 and 4.2 times, respectively, the human dose (BSA).
It is not known whether famciclovir or its active metabolite, penciclovir, cross the placenta to the fetus. Because of the low molecular weight of famciclovir (about 321), passage to the fetus should be expected.
A 1998 non-interventional observational cohort study described the outcomes of pregnancies in women who had been prescribed one or more of 34 newly marketed drugs by general practitioners in England (2). Data were obtained by questionnaires sent to the prescribing physicians one month after the expected or possible date of delivery. Of 1,067 exposed pregnancies, famciclovir was taken during the 1st trimester in seven pregnancies. The outcomes of these pregnancies included one ectopic pregnancy, two missed abortions, and four normal, full-term infants.
The manufacturer (SmithKline Beecham) maintains a pregnancy registry to monitor the maternal-fetal outcomes of women exposed to famciclovir during pregnancy (1). Patients can be registered by calling (800) 366-8900, extension 5231.
Breast Feeding Summary
No studies describing the use of famciclovir during breast feeding, or measuring the amount of drug in human breast milk have been located. The drug is concentrated in the milk of lactating rats, achieving milk concentrations higher than those measured in the plasma (1). Because the drug is probably also excreted into human milk, and because of its tumorigenicity observed in rats and mice (see above) and its potential for other toxicity, women taking famciclovir should probably not breast-feed.
- Product information. Famvir. SmithKline Beecham Pharmaceuticals, 2001.
- Wilton LV, Pearce GL, Martin RM, Mackay FJ, Mann RD. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 1998;105:8829.