Antiviral
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of cidofovir during human pregnancy have been located. It is not known whether the drug crosses the placenta to the fetus, but because of its relatively low molecular weight (approximately 315) passage to the fetus should be expected. Because of the lack of human data, the risk to the human embryo and fetus cannot be assessed. Some risk may exist because of the adverse effects observed at very low doses in the limited animal studies. Despite this risk, the use of cidofovir after the 1st trimester in a pregnant HIV-positive woman with sight-threatening cytomegalovirus (CMV) retinitis may be a rational decision.
FETAL RISK SUMMARY
Cidofovir (HPMPC) is used in the treatment of CMV retinitis in patients with AIDS. The antiviral agent is converted to the active metabolite, cidofovir diphosphate, by intracellular enzymes. In animals, cidofovir is carcinogenic, embryotoxic, and teratogenic.
Cidofovir was carcinogenic in female rats, producing mammary adenocarcinoma at doses as low as about 0.04 times the recommended human dose based on AUC (RHD). Reproductive studies with cidofovir have been conducted with rats and rabbits (1). Both maternal toxicity and embryotoxicity (reduced fetal body weights) were observed at daily IV doses in rats and rabbits that were about 0.12 and 0.24 times the RHD, respectively, administered during organogenesis. The no-observable-effect doses for embryotoxicity in rats and rabbits were about 0.04 and 0.05 times the RHD, respectively. Teratogenic effects, consisting of external, soft tissue, and skeletal malformations (meningocele, short snout, and short maxillary bones), were observed in the fetuses of rabbits given a dose that was about 0.24 times the RHD during organogenesis.
Pregnant mice inoculated intranasally with equine herpesvirus 1 in the 2nd or 3rd week of gestation were treated with a single dose of cidofovir 50 mg/kg SC 1 day prior to inoculation (2). A noninfected, control group of pregnant mice was also treated at a similar gestational time with the same dose of cidofovir. In the infected group, cidofovir significantly reduced the incidence of virus transfer to the fetus and subsequent abortion, a predictable effect of the virus. No obvious toxic effects were observed in either group.
BREASTFEEDING SUMMARY
No reports describing the use of cidofovir during lactation have been located. This antiviral agent should not be used during breastfeeding because of the potential severe toxicity in a nursing infant. Moreover, although no studies have been reported in lactating humans, cidofovir has induced mammary cancer with very low doses in female rats.
In addition, the mother’s clinical status will usually preclude the use of cidofovir during breastfeeding. The only approved indication for this drug is for the treatment of CMV retinitis in patients infected with HIV type 1 (HIV-1). Because HIV-1 is transmitted in milk, breastfeeding is not recommended in developed countries where there are available affordable milk substitutes (3–5).
References
1.Product information. Vistide. Gilead Sciences, 1997.
2.Awan AR, Field HJ. Effects of phosphonylmethoxyalkyl derivatives studied with a murine model for abortion induced by equine herpesvirus 1. Antimicrob Agents Chemother 1993;37:2478–82.
3.Brown ZA, Watts DH. Antiviral therapy in pregnancy. Clin Obstet Gynecol 1990;33:276–89.
4.de Martino M, Tovo P-A, Pezzotti P, Galli L, Massironi E, Ruga E, Floreea F, Plebani A, Gabiano C, Zuccotti GV. HIV-1 transmission through breast-milk: appraisal of risk according to duration of feeding. AIDS 1992;6:991–7.
5.Van de Perre P. Postnatal transmission of human immunodeficiency virus type 1: the breast-feeding dilemma. Am J Obstet Gynecol 1995;173:483–7.