Provigil, Nuvigil Birth Defect Risks Warrant Contraindication for Pregnant Women: FDA Petition

Manufacturer warns about a 15% birth defect rate linked to the drugs, leading Public Citizen to call for the FDA to contraindicate use of Provigil and Nuvigil during pregnancy.

According to a citizen petition filed last week with the U.S. Food and Drug Administration (FDA), stronger warnings should be provided to medical providers indicating that the narcolepsy drugs Provigil and Nuvigil should not be given to pregnant women, due to the risks of birth defects.

The prominent consumer watchdog group Public Citizen filed the Petition on May 28, asking the federal regulators to restrict the use of the medications among women of childbearing age and to add a black box warning about the Provigil and Nuvigil birth defect risks, which would be the strongest warning the FDA can require.

Provigil and Nuvigil Birth Defect Concerns

Provigil (modafinil) and Nuvigil (armodafinil) are stimulants first approved in 2013 for the treatment of narcolepsy, which is a chronic sleep disorder that causes overwhelming daytime drowsiness. However, the medications are also often used off-label to improve cognitive performance.

Both drugs are controlled substances in the U.S. due to the risk of abuse and addiction. In addition, they are pregnancy category C drugs, due to the risk of spontaneous abortions and other potential pregnancy risks.

However, recent studies have also linked the two medications to an increased risk of major congenital birth defects. Teva Pharmaceuticals, the manufacturer, issued a warning to healthcare professionals in June 2019, indicating that Provigil birth defects occurred in 15% of children whose mothers took the medication during pregnancy. That compares to a birth defect rate of only 3% among the general population.

Public Citizen’s petition argues that there is enough evidence, both from human and animal tests, to merit contraindication for women of reproductive age not on birth control, and a black box warning label indicating the drugs are toxic to unborn children.

“Since 2019 this evidence has led regulators in several countries — including Australia, Canada, Ireland, and the United Kingdom — to require contraindicating these drugs during pregnancy and in females of reproductive potential who are not using effective nonhormonal contraceptives and to add this contraindication in the labeling of both drugs,” the petition states. “In contrast, the FDA has not yet taken a similar action to warn U.S. clinicians and patients.”

The group also indicates that off-label use is common, with women taking the drugs to treat attention-deficit hyperactivity disorder, chronic fatigue, multiple sclerosis and Parkinson’s disease.

The petition urges the FDA to move quickly, due to the potential health risks linked to Provigil and Nuvigil’s use by pregnant women.

“The FDA cannot afford any further delay in doing the same to warn patients and clinicians, following the precautionary principle of public health,” Dr. Azza AbuDagga, a health services researcher with Public Citizen said in a press release. “Such action is critically important for the FDA given the severity of the congenital malformations reported due to the use of modafinil and armodafinil so far, the extensive off-label use of these drugs and the fact that nearly half of U.S. pregnancies are unplanned.”

The FDA legally has 180 days to give some kind of response to the petition.