Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States
Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors
Abacavir (Ziagen, ABC)
(Last updated:7/31/2012; last reviewed:7/31/2012)
Abacavir (Ziagen, ABC) is classified as Food and Drug Administration (FDA) Pregnancy Category C.
Animal carcinogenicity studies
Abacavir is mutagenic and clastogenic in some in vitro and in vivo assays. In long-term carcinogenicity studies in mice and rats, malignant tumors of the preputial gland of males and the clitoral gland of females were observed in both species, and malignant hepatic tumors and nonmalignant hepatic and thyroid tumors were observed in female rats. The tumors were seen in rodents at doses that were 6 to 32 times that of human therapeutic exposure.
Reproduction/fertility
No effect of abacavir on reproduction or fertility in male and female rodents has been seen at doses of up to 500 mg/kg/day (about 8 times that of human therapeutic exposure based on body surface area).
Teratogenicity/developmental toxicity
Abacavir is associated with developmental toxicity (decreased fetal body weight and reduced crown-rump length) and increased incidence of fetal anasarca and skeletal malformations in rats treated with abacavir during organogenesis at doses of 1000 mg/kg (about 35 times that of human therapeutic exposure based on area under the curve [AUC]). Toxicity to the developing embryo and fetus (increased resorptions and decreased fetal body weight) occurred with abacavir administration of 500 mg/kg/day to pregnant rodents. The offspring of female rats were treated with 500 mg/kg of abacavir, beginning at embryo implantation and ending at weaning. In these animals, an increased incidence of stillbirth and lower body weight was seen throughout life. However, in the rabbit, no evidence of drug-related developmental toxicity was observed and no increase in fetal malformations was observed at doses up to 700 mg/kg (about 8.5 times that of human therapeutic exposure).
In the Antiretroviral Pregnancy Registry, sufficient numbers of first-trimester exposures to abacavir in humans have been monitored to be able to detect at least a 2-fold increase in risk of overall birth defects. No such increase in birth defects has been observed with abacavir. Among cases of first-trimester abacavir exposure reported to the Antiretroviral Pregnancy Registry, the prevalence of birth defects was 3.0% (25 of 823 births; 95% confidence interval [CI], 2.0%–4.5%) compared with 2.7% in the U.S. population, based on Centers for Disease Control and Prevention (CDC) surveillance.1
Placental and breast milk passage
Abacavir crosses the placenta and is excreted into the breast milk of lactating rats.
Human studies in pregnancy
A Phase I study of abacavir in pregnant women indicates that the AUC drug concentration during pregnancy was similar to that at 6 to 12 weeks postpartum and in non-pregnant individuals.2 Thus, no dose adjustment for abacavir is needed during pregnancy. Serious hypersensitivity reactions have been associated with abacavir therapy in non-pregnant adults and have rarely been fatal; symptoms include fever, skin rash, fatigue, and gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain. Abacavir should not be restarted following a hypersensitivity reaction because more severe symptoms will occur within hours and may include life-threatening hypotension and death.
References
- Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral pregnancy registry international interim report for 1 Jan 1989 - 31 January 2012. Wilmington, NC: Registry Coordinating Center; 2012. Available at http://www.APRegistry.com.
- Best BM, Mirochnick M, Capparelli EV, et al. Impact of pregnancy on abacavir pharmacokinetics. AIDS. Feb 28 2006;20(4):553-560. Available at http://www.ncbi.nlm.nih.gov/pubmed/16470119.