FDA Issues Safety Alert for Drug Linked to Potential Birth Defects

Serious cases of neural tube birth defects, including spina bifida, have been reported in babies born to women with HIV being treated with dolutegravir. In response, safety alerts have been issued by the FDA, and the European Medicines Agency (EMA).

According to an ongoing observational study in Botswana, women who received dolutegravir at the time of becoming pregnant or early in the first trimester appear to be at higher risk for birth defects involving the brain, spine, and spinal cord.^1-2 The study has looked at babies born to 11,558 women with HIV in Botswana. The study’s current data suggest that 0.9% of these babies (4 of 426) whose mothers became pregnant while taking dolutegravir had a neural tube defect, compared with 0.1% of babies (14 of 11,173) whose mothers were taking other HIV medications.²

There are no reported cases of babies born with neural tube defects to women that started dolutegravir later in the pregnancy cycle, but the FDA is continuing to investigate the safety issue.¹ Final results of the Botswana study are expected in about a year.²

Dolutegravir is an antiretroviral medicine used in combination with other antiretroviral drugs to treat HIV. On the market for the 5 years, dolutegravir was approved by the FDA in 2013. It is available as a single ingredient product (Tivicay), and as a fixed dose combination tablet (Juluca, and Triumeq) with other medicines.¹

The treatment works by blocking integrase, an HIV enzyme, to prevent the virus from multiplying, and can reduce the amount of HIV in the body.¹ According to the FDA and the EMA, patients should not stop taking dolutegravir without first speaking with a prescriber, as stopping the treatment can cause the HIV infection to become worse.

In addition, both agencies have warned that in women who are pregnant, stopping a regimen containing dolutegravir without switching to alternative HIV medicines could cause the amount of their virus to increase, and spread HIV to their baby.

The FDA and EMA recommend that women of childbearing age speak with their healthcare professionals about antiretroviral medicines that do not contain dolutegravir, even if they are not pregnant. The recommendation was made due to the early development of neural tube birth defects that have been shown in studied cases, which sometimes occur before a woman knows she is pregnant.

The FDA also recommends that women of childbearing age who choose to take a drug regimen containing dolutegravir consistently use effective contraception while on the HIV treatment. A pregnancy test should be taken prior to starting a dolutegravir-containing medication.

Healthcare professionals should inform women of childbearing age about the potential risk of neural tube birth defects when dolutegravir is taken at the time of conception and early in pregnancy. The risks and benefits of dolutegravir should be weighed when prescribing the drug, and alternative antiretroviral medications should be considered.

References

• U.S. Food and Drug Administration. FDA drug safety communication: FDA to evaluate potential risk of neural tube birth defects with HIV medicine dolutegravir (Juluca, Tivicay, Triumeq). FDA website. https://www.fda.gov/Drugs/DrugSafety/ucm608112.htm?utm_campaign=HIV%20Updates%20-%20FDA%20to%20evaluate%20potential%20risk%20of%20neural%20tube%20birth%20defects&utm_medium=email&utm_source=Eloqua&elqTrackId=be4c6a24b0774719b5bc9ad87ed43ccf&elq=ba13947022e. Published May 18, 2018. Accessed May 21, 2018.
• European Medicines Agency. New study suggests risk of birth defects in babies born to women on HIV medicine dolutegravir [news release]: London, England; May 18, 2018. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2018/05/WC500249225.pdf. Accessed May 21, 2018.