This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B1
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 of birth defects and miscarriage.

Comments:
-A pregnancy exposure registry is available.
-This drug has not been studied in pregnant patients.
-While insufficient human data are available to assess the risk of neural tube defects with exposure to this drug during pregnancy, neural tube defects were reported with dolutegravir (another integrase inhibitor).
-The benefit-risk of using this drug should be discussed with patients of childbearing potential or during pregnancy.
-Cabotegravir has been detected in systemic circulation for up to 12 months or longer after administration of the last injection.

Animal studies have failed to reveal evidence of teratogenicity, but have revealed evidence of fetal harm at exposures higher than for therapeutic doses. After oral dosing to pregnant rabbits, at doses with exposures up to 0.66 times the exposure at the maximum recommended human dose (MRHD) of 30 mg (about 0.7 times the exposure in humans at the recommended human dose [RHD]), no adverse developmental outcomes or drug-related fetal toxicities were observed. In rats, at exposures 28 times the exposures at the MRHD of 30 mg oral or 400 mg IM (greater than 28 times the exposure in humans at the RHD), this drug was associated with decreased fetal weight, delayed onset of parturition, and increased number of stillbirths and neonatal mortalities immediately after birth, but there were no effects on fetal viability when fetuses were delivered by caesarean; a lower dose of this drug, at exposures greater than 10 times the exposure at the MRHD of 30 mg oral or 400 mg IM (about 13 times the exposure in humans at the RHD), showed no drug-related fetal toxicities and was not associated with delayed parturition or neonatal mortality in rats; no drug-related fetal malformations were observed at any dose. In rats, this drug crossed the placental barrier and was detected in fetal tissue. There are no controlled data in human pregnancy.

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

Data from a birth outcome surveillance study in Botswana showed that dolutegravir (another integrase inhibitor) was associated with increased risk of neural tube defects when administered at time of conception and in early pregnancy. Data from clinical trials are insufficient to address this risk with cabotegravir.

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.

See references

HIV-1 Treatment: Breastfeeding is not recommended during use of this drug.
HIV-1 Preexposure Prophylaxis: Benefit should outweigh risk.

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.
-If cabotegravir is present in human milk, residual exposures may remain for up to 12 months or longer after administration of the last injection.
-The effects in the nursing infant are unknown; potential for HIV-infected infants developing viral resistance and breastfed infants developing side effects similar to those in adults
-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