Animal studies have failed to reveal evidence of adverse developmental outcomes with exposures up to about 4 times the maximal recommended human dose (MRHD) of 1200 mg; an increased incidence of fetal supernumerary ribs was seen in offspring of rats at dose of 600 mg/kg/day (systemic exposures about 3 times higher than exposures at MRHD of 1200 mg), but not at dose of 1000 mg/kg/day in rabbits (systemic exposures about 4 times higher than exposures at MRHD of 1200 mg). There are no controlled data in human pregnancy; however, a moderate amount of data in pregnant women (between 300 and 1000 pregnancy outcomes from first trimester exposure) showed no malformations, fetotoxicity, or neonatal toxicity with the 400 mg film-coated tablets twice a day.

Placental transfer to the fetus has been reported as high (cord blood/maternal delivery plasma drug ratio greater than 0.6) with this drug; in 3 studies, cord blood/maternal plasma ratios were 1.5, 1.48 (range: 0.32 to 4.33), and 1.21.

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 over 775 exposures to raltegravir-containing regimens (over 400 exposed in the first trimester; over 375 exposed in the second/third trimester) resulting in live births; there was no difference between this drug and overall birth defects 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 with first trimester and second/third trimester exposures was 3.1% and 3.8%, respectively.

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.

400 mg film-coated tablets, chewable tablets, and granules for oral suspension: This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.
600 mg film-coated tablets: Use is not recommended.

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

Risk summary: Available data show no difference in rate of overall 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.
-No data available on the use of the chewable tablets or granules for oral suspension in pregnant patients.
-No data available on the use of 1200 mg (using the 600 mg film-coated tablets) once a day in pregnant patients; once-daily dosing (i.e., two 600 mg film-coated tablets) is not recommended during pregnancy.

See references

In rats administered 600 mg/kg/day orally from gestation day 6 to lactation day 14, drug levels in milk were about 3 times that of maternal plasma drug levels at 2 hours after dosing on lactation day 14.

Breastfeeding is not recommended during use of this drug.

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

Comments:
-No published data available on use of this drug during breastfeeding.
-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.

See references