Animal studies have failed to reveal evidence of embryofetal toxicity, an effect on reproductive function, or clinically significant teratogenicity; after oral administration, no evidence of significant embryofetal toxicity was observed at exposures 15 (rats) and 70 (rabbits) times higher than the exposure in humans at the recommended dose (25 mg/day). There are limited controlled data in human pregnancy; a moderate amount of data on pregnant women (between 300 and 1000 pregnancy outcomes) showed no malformative toxicity, fetotoxicity, or neonatal toxicity.

Placental transfer to the fetus has been reported as moderate to high (cord blood/maternal delivery plasma drug ratio at least 0.3); in studies of pregnant women using this drug, the cord blood-to-maternal plasma ratio ranged from 0.3 to 0.98.

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

The APR has received prospective reports of over 800 exposures to rilpivirine-containing regimens (over 600 exposed in the first trimester; over 200 exposed in the second/third trimester) resulting in live births; there was no significant difference in the overall risk of birth defects for this drug compared with the background birth defect rate of 2.7% in the US reference population. Enough first-trimester exposures have been monitored to detect at least a 2-fold increased risk of overall birth defects; no such increases detected. The prevalence of birth defects/live births with first trimester and second/third trimester exposures was 1.6% and 1.4%, respectively.

In a clinical trial, this drug (in combination with background regimen) was evaluated in 19 HIV-1-infected pregnant women (who were using a rilpivirine-based regimen at time of enrollment) during the second and third trimesters and postpartum; 12 patients completed the trial through postpartum period (6 to 12 weeks after delivery) and 6 pregnancy outcomes were missing. Total drug exposure was about 30% to 40% lower during pregnancy compared with postpartum (6 to 12 weeks); protein binding was similar (greater than 99%) during the second and third trimester and postpartum. One patient discontinued the trial after spontaneous termination of pregnancy at 25 weeks gestation due to suspected premature rupture of membranes. Of the 12 patients who were virologically suppressed at baseline (less than 50 copies/mL), virologic response was sustained in 10 patients (83.3%) through the third trimester visit and in 9 patients (75%) through the 6- to 12-week postpartum visit; virologic outcomes during the third trimester visit were missing for 2 patients who were withdrawn (1 was nonadherent to study drug; 1 withdrew consent). Of the 10 infants with HIV test results available (born to 10 HIV-1-infected pregnant patients), all had negative HIV-1 test results at time of delivery and up to 16 weeks postpartum; all 10 infants received antiretroviral prophylaxis with zidovudine. Rilpivirine was well tolerated during pregnancy and postpartum (no new safety findings compared with known safety profile in HIV-1-infected adults).

AU TGA pregnancy category B1: 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 not shown evidence of an increased occurrence of fetal damage.

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 clearly needed and the benefit outweighs the risk to the fetus.
-IM injection: This drug should not be used during pregnancy unless the benefit outweighs the risk.

AU TGA pregnancy category: B1
US FDA pregnancy category: Not assigned.

Risk summary: Available data show no difference in overall risk of birth defects for this drug compared with background rate for major birth defects in the US reference population.

Comments:
-A pregnancy exposure registry is available.
-In a clinical trial, total drug exposures were usually lower during pregnancy compared to postpartum; viral load should be monitored closely.
-According to some authorities: Women of childbearing potential should use adequate contraception; this drug is unlikely to decrease the efficacy of oral contraceptives.
-IM injection: An alternative oral regimen should be considered (according to current treatment guidelines); this drug may remain in systemic circulation for up to 4 years in some patients after stopping this formulation.

See references

Breastfeeding is not recommended during use of this drug.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-No published data available regarding use during breastfeeding; an alternate agent may be preferred.
-The effects in the nursing infant are unknown; potential for HIV-infected infants developing viral resistance and breastfed infants developing 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.
-Secretion into human milk is expected based on animal data but has not been confirmed in humans; this drug may be present in human milk for up to 4 years in some patients after stopping the IM injection.

See references