Dolutegravir (Tivicay▼, Triumeq▼, Juluca▼): updated advice on increased risk of neural tube defects

Updated safety recommendations have been issued as part of the European review evaluating cases of neural tube defects in babies born to mothers who became pregnant while taking the HIV medicine dolutegravir. Evidence collected as more women have given birth while on dolutegravir treatment shows a smaller increased risk than previously thought, almost comparable to other HIV drugs. The previous restrictions against use in pregnancy are no longer in place – inform women of the potential risk of neural tube defects with dolutegravir and discuss the benefits and risks of continuing treatment if a woman plans pregnancy.

From:
Medicines and Healthcare products Regulatory Agency
Published
22 October 2020
Therapeutic area:
Infectious disease and Pregnancy

Advice for healthcare professionals:

  • counsel women of childbearing potential about the possible risk of neural tube defects with dolutegravir, including consideration of effective contraceptive measures

  • discuss the benefits and the risks of continuing treatment with dolutegravir to women who are trying to become pregnant

  • if a pregnancy is confirmed in the first trimester while a patient is on dolutegravir, the benefits and risks of continuing dolutegravir versus switching to another antiretroviral regimen should be discussed with the patient, taking into account the gestational age and the critical time period of neural tube defect development

  • report any suspected adverse drug reactions associated with dolutegravir to the Yellow Card scheme

Risk of neural tube defects

In June 2018 preliminary results from an observational study suggested an increased risk of neural tube defects in infants born to women who took dolutegravir at the time of conception. While a review of this signal was ongoing, we issued a Drug Safety Update article asking healthcare professional not to prescribe dolutegravir to women who are trying to become pregnant. The product information for dolutegravir was amended with these recommendations and a letter was sent to healthcare professionals by the manufacturer.

The study is ongoing and since the article in 2018, additional women were included in the continuing analysis. For a total of 19,361 babies born to women with HIV in Botswana, updated data showed 0.19% (95% CI 0.09–0.40) of babies (7 of 3,591) whose mothers became pregnant while taking dolutegravir had a neural tube defect, compared with 0.11% (0.07–0.17) of babies (21 of 19,361) whose mothers took other HIV medicines.

The latest review also investigated cases of birth defects in babies born to women who took dolutegravir during pregnancy reported from the Antiretroviral Pregnancy Registry with 660 women exposed to dolutegravir during pregnancy. These data do not indicate an increased risk of major birth defects associated with dolutegravir treatment (absolute risk difference of neural tube defects between dolutegravir and other HIV treatment at conception of 0.08 [95% –CI 0.03 to 0.30]). However, because of the rarity of the neural tube defects, these data are insufficient to completely rule out any risk. Changes will be made to product information advice to reflect the latest review of data.

The review of the study is ongoing. Further advice will be communicated as appropriate as important new information becomes available.

Background

▼Dolutegravir is an integrase inhibitor indicated in combination with other anti-retroviral medicinal products for the treatment of HIV in adults, adolescents, and children older than 6 years. In the EU, dolutegravir has been authorised since 2014. It is marketed on its own as Tivicay and in combination with lamivudine and abacavir as Triumeq or in combination with rilpivirine hydrochloride as Juluca. Further information on these medicines can be found in the Summaries of Product Characteristics.

Report on a Yellow Card

Any suspected adverse drug reactions with dolutegravir (Tivicay▼, Triumeq▼, Juluca▼) should be reported without delay on a Yellow Card.

Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

Please report to the Yellow Card scheme suspected adverse reactions associated with medicines taken during pregnancy or breastfeeding experienced by women or the baby or child.

Any patients, caregivers, or healthcare professionals can report a Yellow Card when they suspect a medication used during pregnancy has caused an adverse reaction or abnormal pregnancy outcome.

Article citation: Drug Safety Update volume 14, issue 3: October 2020: 4.

Updates to this page

Published 22 October 2020
Contents