A
Antiviral
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
The animal data suggest moderate risk. Although the human pregnancy experience does not suggest a risk of structural anomalies, other potential developmental toxicities require study. Antiretroviral nucleosides have been shown to have a direct dose-related cytotoxic effect on preimplantation mouse embryos (see Didanosine, Stavudine, Zalcitabine, and Zidovudine). This toxicity has not been studied in humans. Mitochondrial dysfunction in offspring exposed in utero or postnatally to nucleoside reverse transcriptase inhibitors (NRTIs) has been reported (see Lamivudine and Zidovudine), but these findings are controversial and require confirmation. However, if indicated, the drug should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Abacavir is a synthetic carbocyclic nucleoside analog that is converted by cellular enzymes to the active metabolite, carbovir triphosphate. It is an NRTI used for the treatment of HIV type 1 (HIV-1). Other drugs in this class are didanosine, lamivudine, stavudine, zalcitabine, and zidovudine (1).
In reproduction studies, doses of abacavir up to 8 times the human therapeutic dose (HTD) based on BSA had no effect on the fertility or mating performance of male and female rats. However, embryo toxicity (increased resorptions, decreased body weight) was observed. During organogenesis, doses up to 35 times the human exposure based on AUC (about 16 times the HTD) resulted in fetal growth restriction (reduced body weight and crown–rump length), as well as increased incidences of fetal anasarca and skeletal malformations. Offspring exposed from implantation through weaning had an increased incidence of stillbirth and survivors had decreased body weights throughout life. In contrast, no developmental toxicity or malformations were observed in rabbits at doses up to 8.5 times the human exposure based on AUC (1).
Abacavir crosses the human placenta. In four women being treated for multiple agents for HIV infection, the mean abacavir cord:maternal blood ratio was 1.03 at a mean of 3.5 hours (range 0.4–9.0 hours) after a dose (dose not specified) and the amniotic fluid concentration in one woman was 1.6 mg/L (2). These results are consistent with the relatively low molecular weight (about 671) and high lipophilic properties of abacavir. In an ex vivo human placental model, the antiviral agent readily crossed to the fetal side with a high clearance index of about 50% that of antipyrine (3). No accumulation of the drug was found on the fetal side.
The Antiretroviral Pregnancy Registry reported, for the period January 1989 through July 2009, prospective data (reported before the outcomes were known) involving 4702 live births that had been exposed during the 1st trimester to one or more antiretroviral agents (4
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
