Animal studies have failed to reveal evidence of embryofetal toxicity at doses resulting in exposures about 2 times (rats) and 0.8 times (rabbits) human exposures at maximum recommended human dose (MRHD) of this drug alone or 0.7 times (rats) and 0.3 times (rabbits) human exposures at MRHD of this drug plus ritonavir; the incidence of abortion was increased in rabbits administered a maternally toxic dose of this drug. In rabbits administered lower oral doses of amprenavir (producing about 1/20th the exposure observed at MRHD), increased abortions and increased incidence of minor skeletal variations (deficient ossification of femur, humerus, trochlea) were observed. There are no controlled data in human pregnancy.

Placental transfer to the fetus has been reported as low (cord blood/maternal delivery plasma drug ratio less than 0.3). In 2 small studies of women using this drug during pregnancy, the ratio of amprenavir level in cord blood to amprenavir level in maternal plasma at time of delivery was 0.24 (range: 0.06 to 0.93) in 1 study and 0.27 in the other study.

With ritonavir boosting, the AUC was lower during the third trimester; however, exposure was higher during the third trimester with boosting than in nonpregnant adults without boosting, and trough levels were adequate during the third trimester for patients without protease inhibitor resistance mutations. According to some experts, this drug must be used with low-dose ritonavir boosting during pregnancy (using the twice-daily regimen).

To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com

The APR has received prospective reports of 143 exposures to regimens containing this drug (107 exposed in the first trimester; 36 exposed in the second/third trimester) resulting in live births; 4 birth defects have been reported. Too few exposures to this drug have been monitored to accurately calculate prevalence of birth defects in exposed cases.

During a retrospective study, fosamprenavir-based highly active antiretroviral therapy was well-tolerated in 9 pregnant women and most achieved favorable immunologic and virologic responses. Good birth outcomes and no significant side effects were reported in infants. No mother-to-child transmission of HIV was detected.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus; use of unboosted fosamprenavir or once-daily dosing with ritonavir boosting is not recommended during pregnancy.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk summary: Insufficient data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-A pregnancy exposure registry is available.
-Females of Reproductive Potential: Use of this drug may reduce the efficacy of combined hormonal contraceptives; patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method.

See references

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug may be preferred.

Excreted into human milk: Unknown
Excreted into animal milk: Yes (amprenavir)

Comments:
-The effects in the nursing infant are unknown; potential for HIV-infected infants developing viral resistance and breastfed infants developing serious side effects
-The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected.
-Local guidelines should be consulted if replacement feeding is not an option.

See references