Tivicay Use In Pregnancy & Lactation

Pregnancy: TIVICAY should be used during pregnancy only if the expected benefit justifies the potential risk to the foetus. Women of childbearing potential (WOCBP) should be informed about the potential risk of neural tube defects with dolutegravir and counselled about the use of effective contraception. It is recommended that pregnancy testing is conducted prior to initiation of TIVICAY. If there are plans to become pregnant or if pregnancy is confirmed within the first trimester while on TIVICAY, the risks and benefits of continuing TIVICAY versus switching to another antiretroviral regimen should be discussed with the patient. Factors to consider should include feasibility of switching, tolerability, ability to maintain viral suppression, actual gestational age, risk of transmission to the infant and the available data around the potential risk of neural tube defects and other pregnancy outcomes for dolutegravir and alternative antiretroviral drugs.
In a birth outcome surveillance study in Botswana, numerically higher rate of neural tube defects was identified with exposure to dolutegravir compared to non-dolutegravir-containing antiretroviral regimens at the time of conception, however, the difference was not statistically significant. Seven cases of neural tube defects were reported in 3,591 deliveries (0.19%) to mothers taking dolutegravir-containing regimens at the time of conception, compared with 21 cases in 19,361 deliveries (0.11%) to mothers taking non-dolutegravir-containing regimens at the time of conception (Prevalence Difference 0.09%; 95% CI 0.03, 0.30).
In the same study, an increased risk of neural tube defects was not identified in women who started dolutegravir during pregnancy. Two out of 4,448 deliveries (0.04%) to mothers who started dolutegravir during pregnancy had a neural tube defect, compared with five out of 6,478 deliveries (0.07%) to mothers who started non-dolutegravir-containing regimens during pregnancy.
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 most neural tube defects occur within the first 4 weeks of foetal development (approximately 6 weeks after the last menstrual period) this potential risk would concern women exposed to dolutegravir at the time of conception and in early pregnancy.
Data analysed to date from other sources including the Antiretroviral Pregnancy Registry, clinical trials, and post-marketing data are insufficient to address the risk of neural tube defects with dolutegravir.
More than 1,000 outcomes from second and third trimester exposure in pregnant women indicate no evidence of increased risk of adverse birth outcomes.
In animal reproductive toxicity studies, no adverse development outcomes, including neural tube defects, were identified (see Pharmacology: Toxicology: Preclinical safety data under Actions).
TIVICAY use during pregnancy has been evaluated in the Antiretroviral Pregnancy Registry (APR) in over 600 women (as of July 2019). Available human data from the APR do not show an increased risk of major birth defects for dolutegravir compared to the background rate (see Pharmacology: Pharmacodynamics under Actions).
Dolutegravir readily crosses the placenta in humans. In HIV-infected pregnant women, the median (range) foetal umbilical cord concentrations of dolutegravir were 1.28 (1.21 to 1.28) fold greater compared with maternal peripheral plasma concentrations.
There is insufficient information on the effects of TIVICAY on neonates.
Breast-feeding: Dolutegravir is excreted in human milk in small amounts. In an open-label randomised study in which HIV-infected treatment-naïve pregnant women were administered a dolutegravir-based regimen until two weeks post-partum, the median (range) dolutegravir breast milk to maternal plasma ratio was 0.033 (0.021 to 0.050). 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).