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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

Protease Inhibitors

Fosamprenavir (Lexiva, FPV)

(Last updated: August 6, 2015; last reviewed: August 6, 2015)

Fosamprenavir is classified as Food and Drug Administration Pregnancy Category C.

Animal Studies

Fosamprenavir and amprenavir were neither mutagenic nor clastogenic in a series of in vitro and animal in vivo screening tests. Carcinogenicity studies of fosamprenavir showed an increase in the incidence of hepatocellular adenomas and hepatocellular carcinomas at all doses tested in male mice and at the highest dose tested in female mice. In rats, the incidence of hepatocellular adenomas and thyroid follicular cell adenomas in males (all doses tested) and in females (two highest doses tested) was also increased. Repeat dose studies in rats produced effects consistent with enzyme activation, which predisposes rats, but not humans, to thyroid neoplasms. In rats only, there was an increase in interstitial cell hyperplasia at higher doses and an increase in uterine endometrial adenocarcinoma at the highest dose tested. The incidence of endometrial findings was slightly increased over concurrent controls but was within background range for female rats. Thus, the relevance of the uterine endometrial adenocarcinomas is uncertain. Exposures in the carcinogenicity studies were 0.3- to 0.7 (mice) and 0.7- to 1.4 (rats) times those in humans given 1,400 mg twice daily of fosamprenavir alone and were 0.2- to 0.3 (mice) and 0.3- to 0.7 (rats) times those in humans given 1,400 mg once daily of fosamprenavir plus 200 mg ritonavir once daily or 0.1- to 0.3 (mice) and 0.3- to 0.6 (rats) times those in humans given 700 mg fosamprenavir plus 100 mg ritonavir twice daily.

No impairment of fertility or mating was seen in rats at doses providing 3 to 4 times the human exposure to fosamprenavir alone or exposure similar to that with fosamprenavir and ritonavir dosing in humans. No effect was seen on the development or maturation of sperm in rats at these doses.

Teratogenicity/Developmental Toxicity
Fosamprenavir was studied in rabbits at 0.8 times and in rats at twice the exposure in humans to fosamprenavir alone and at 0.3 (rabbits) and 0.7 (rats) times the exposure in humans to the combination of fosamprenavir and ritonavir. In rabbits administered fosamprenavir (alone or in combination), the incidence of abortion was increased. In contrast, administration of amprenavir at a lower dose in rabbits was associated with abortions and an increased incidence of minor skeletal variations from deficient ossification of the femur, humerus, and trochlea. Fosamprenavir administered to pregnant rats (at twice human exposure) was associated with a reduction in pup survival and body weights in rats. F1 female rats had an increased time to successful mating, an increased length of gestation, a reduced number of uterine implantation sites per litter, and reduced gestational body weights, compared to controls. 

Placental and Breast Milk Passage
Amprenavir is excreted in the milk of lactating rats.

Human Studies in Pregnancy

Data on fosamprenavir in pregnant women are very limited. Fosamprenavir pharmacokinetic data have been reported in 26 women during pregnancy and postpartum. Following standard dosing with fosamprenavir 700 mg and ritonavir 100 mg, fosamprenavir area under the curve and 12-hour trough concentration were somewhat lower during pregnancy and higher postpartum, compared to historical data. Fosamprenavir exposure during pregnancy appeared to be adequate for patients without protease inhibitor resistance mutations.
 Placental and Breast Milk Passage
 In a small study of women receiving fosamprenavir during pregnancy, the median (range) amprenavir concentration in cord blood was 0.27 (0.09–0.60) µg/mL, and the median (range) ratio of amprenavir concentration in cord blood to that in maternal plasma at the time of delivery was 0.24 (0.06–0.93).1 A second small study in pregnancy yielded a similar mean ratio (95% confidence interval) of amprenavir concentration in cord blood to that in maternal plasma at the time of delivery of 0.27 (0.24, 0.30).2 Whether amprenavir is excreted in human breast milk is unknown.

Teratogenicity/Developmental Toxicity
The number of first-trimester exposures to fosamprenavir that have been monitored to date in the Antiretroviral Pregnancy Registry is insufficient to allow conclusions to be drawn regarding the risk of birth defects.3


  1. Capparelli EV, Stek A, Best B, et al. Boosted fosamprenavir pharmacokinetics during pregnancy. Presented at: 17th Conference on Retroviruses and Opportunistic Infections. 2010. San Francisco, CA.
  2. Cespedes MS, Castor D, Ford SL, et al. Steady-state pharmacokinetics, cord blood concentrations, and safety of ritonavir-boosted fosamprenavir in pregnancy. J Acquir Immune Defic Syndr. 2013;62(5):550-554. Available at
  3. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry international interim report for 1 Jan 1989 - 31 July 2014. Wilmington, NC: Registry Coordinating Center. 2014. Available at

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