Antiviral
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
One 1992 review suggested that foscarnet would be a first-line agent for pregnant HIV-positive patients with sight-threatening cytomegalovirus (CMV) retinitis (1). Because of the frequent occurrence of renal toxicity experienced with foscarnet in adults, however, the reviewer recommended frequent antepartum testing of the fetus and close monitoring of the amniotic fluid volume to observe for fetal renal toxicity.
FETAL RISK SUMMARY
Foscarnet has antiviral in vitro activity against all known herpes viruses, including CMV, herpes simplex virus (HSV) types 1 and 2, human herpesvirus 6, Epstein–Barr virus, and varicella–zoster virus (2). The drug is also active in vitro against HIV (3). It is used in patients with AIDS who have CMV retinitis or in immunocompromised patients with mucocutaneous acyclovir-resistant HSV infections.
Reproductive studies in pregnant rats with SC doses of 150 mg/kg/day, approximately one-eighth the estimated maximum daily human exposure based on AUC comparison, caused an increase in the frequency of skeletal malformations or variations. Administration to pregnant rabbits with 75 mg/kg/day, approximately one-third the human dose (AUC comparison), produced similar skeletal defects or variations. In addition, dose-related genotoxic effects were seen in two in vitro tests and in one in vivo test in mice (2).
It is not known if foscarnet crosses the human placenta. The molecular weight (about 300 for the sodium salt) is low enough that passage to the fetus should be expected.
Only one report describing the use of foscarnet during human pregnancy has been located. A 21-year-old woman at 18 weeks’ gestation was treated with an 8-day course of IV foscarnet (total dose 43.8 g) for severe, genital acyclovir-resistant HSV type 2 (3). The patient also had a 3-year history of HIV disease that was being treated with saquinavir, lamivudine, and zidovudine. After discharge from the hospital, repeat cultures yielded HSV type 2 sensitive to acyclovir and she was treated with oral doses of this antiviral agent for the remainder of her pregnancy. She underwent a cesarean section at term to deliver a healthy, HIV-negative, female infant who was developing normally at 1 year of age. The authors, citing information received from the manufacturer, briefly reviewed two other cases of IV foscarnet therapy. In one case, a HIV-negative woman with acyclovir-resistant HSV encephalitis and retinitis had been treated with foscarnet (60 mg/kg IV every 8 hours) for 17 days starting at 32 weeks’ gestation. She eventually delivered a healthy infant at term. The second case involved a HIV-positive patient who was treated with foscarnet (40 mg/kg IV every 8 hours) for genital HSV type 2 beginning at 29 weeks’ gestation. No further information was available on this case (3).
BREASTFEEDING SUMMARY
No reports describing the use of foscarnet during human lactation have been located. Because excretion into human milk most likely occurs, and because of the potentially severe toxicity that might occur in a nursing infant, women receiving foscarnet should not breastfeed.
References
1.Watts DH. Antiviral agents. Obstet Gynecol Clin North Am 1992;19:563–85.
2.Product information. Foscavir. AstraZeneca, 2001.
3.Alvarez-McLeod A, Havlik J, Drew KE. Foscarnet treatment of genital infection due to acyclovir-resistant herpes simplex virus type 2 in a pregnant patient with AIDS: case report. Clin Infect Dis 1999;29:937–8.