Pregnancy: Dolutegravir should be used during pregnancy only if the expected benefit justifies the potential risk to the foetus. Women of childbearing potential (WOCBP) should undergo pregnancy testing before initiation of dolutegravir and dolutegravir should be avoided in the first trimester. WOCBP who are taking dolutegravir should use effective contraception throughout treatment.
There are no adequate and well-controlled studies of dolutegravir in pregnant women. The effect of dolutegravir on human pregnancy is unknown.
In a preliminary analysis of an ongoing birth outcome surveillance study in Botswana there have been 4 cases (as of May 2018) of neural tube defects reported in 426 infants born to mothers who were exposed to dolutegravir-containing regimens from the time of conception. In the same study, no infant born to a woman who started dolutegravir during pregnancy had a neural tube defect, out of 2,824 women. A causal relationship of these events to the use of dolutegravir has not been established. The incidence of neural tube defects in the general population ranges from 0.5-1 case per 1,000 live births. As neural tube defects occur within the first 4 weeks of foetal development (at which time the neural tubes are sealed) this potential risk would concern women exposed to dolutegravir at the time of conception and in early pregnancy.
Although there is limited experience with the use of dolutegravir in pregnancy, the available data from other sources including the Antiretroviral Pregnancy Registry (including over 120 completed pregnancies as of May 2018 in mothers exposed to dolutegravir at the time of conception), clinical trials and post-marketing use has not indicated a similar potential safety issue.
In animal reproductive toxicity studies, no adverse development outcomes, including neural tube defects, were identified. Dolutegravir was shown to cross the placenta in animals (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Breast-feeding: It is unknown whether dolutegravir is excreted in human milk. Available toxicological data in animals has shown excretion of dolutegravir in milk. In lactating rats that received a single oral dose of 50 mg/kg at 10 days postpartum, dolutegravir was detected in milk at concentrations typically higher than blood. It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Fertility: There are no data on the effects of dolutegravir on human male or female fertility. Animal studies indicate no effects of dolutegravir on male or female fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).