Pregnancy & Lactation : הריון/הנקה

4.6   Fertility, pregnancy and lactation

Women of childbearing potential
Women of childbearing potential should be counselled about the potential risk of neural tube defects with dolutegravir (a component of Juluca, see below), including consideration of effective contraceptive measures.

If a woman plans pregnancy, the benefits and the risks of continuing treatment with Juluca should be discussed with the patient.

Pregnancy

Lower exposures of dolutegravir and rilpivirine were observed during pregnancy (see sections 5.1, 5.2). In phase 3 studies, lower rilpivirine exposure, similar to that seen during pregnancy, has been associated with an increased risk of virological failure. The use of Juluca during pregnancy is not recommended.

The safety and efficacy of a dual regimen has not been studied in pregnancy.

Human experience from a birth outcome surveillance study in Botswana shows a small increase of neural tube defects; 7 cases in 3,591 deliveries (0.19%; 95% CI 0.09%, 0.40%) to mothers taking dolutegravir- containing regimens at the time of conception compared to 21 cases in 19,361 deliveries (0.11%: 95% CI 0.07%, 0.17%) to women exposed to non-dolutegravir regimens at the time of conception.

The incidence of neural tube defects in the general population ranges from 0.5-1 case per 1,000 live births (0.05-0.1%). Most neural tube defects occur within the first 4 weeks of embryonic development after conception (approximately 6 weeks after the last menstrual period).

Data analysed from the Antiretroviral Pregnancy Registry do not indicate an increased risk of major birth defects in over 600 women exposed to dolutegravir during pregnancy but are currently insufficient to address the risk of neural tube defects.

In animal reproductive toxicology studies with dolutegravir, no adverse development outcomes, including neural tube defects, were identified (see section 5.3).

More than 1000 outcomes from exposure to dolutegravir during second and third trimester pregnancy indicate no evidence of increased risk of foetal/neonatal toxicity.

Dolutegravir crosses the placenta in humans. In pregnant women living with HIV, the median foetal umbilical cord concentration of dolutegravir was approximately 1.3-fold greater compared with the maternal peripheral plasma concentration.

There is insufficient information on the effects of dolutegravir on neonates.

Animal studies with rilpivirine do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Breast-feeding

It is unknown if rilpivirine is excreted in human milk. Available toxicological data in animals has shown excretion of rilpivirine in milk. Dolutegravir is excreted in human milk in small amounts (a median dolutegravir breast milk to maternal plasma ratio of 0.033 has been shown). There is insufficent information on the effects of dolutegravir in newborns/infants.

It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.

Fertility

There are no data on the effects of dolutegravir or rilpivirine on human male or female fertility. Animal studies indicate no clinically relevant effects on male or female fertility (see section 5.3).