FDA Must Warn About Major Fetal Harm for Two Common Wakefulness-Promoting Drugs
WASHINGTON, D.C. – The U.S. Food and Drug Administration (FDA) should require an explicit warning against the use of two widely prescribed oral wakefulness-promoting drugs during pregnancy – modafinil (Provigil and generics) and armodafinil (Nuvigil and generics) – both of which have been linked to major congenital malformations, Public Citizen reiterated today in a supplemental petition submitted to the agency.
The filing is based on the latest results from an industry-funded analysis of final, 14-year data from the Nuvigil and Provigil Pregnancy Registry. The analysis found that 13% of an overall 156 fetuses exposed to modafinil or armodafinil during pregnancy and followed prospectively developed major congenital malformations, compared with just 3% in the general U.S. population. The malformations involved the musculoskeletal system, central nervous system, male genitalia, heart, cleft lip or palate, chromosomal anomalies, and other structural abnormalities.
“Drug regulators in Australia, Canada, Ireland, and the U.K. took the lead years ago on warning against the use of modafinil and armodafinil during pregnancy. It is inconceivable that the FDA has not followed suit, especially now that the drugs have been linked to a fourfold higher rate of major congenital malformations,” said Azza AbuDagga, Ph.D., health services researcher for Public Citizen, who prepared the petitions. “The FDA cannot afford any additional delay in mandating revisions to the labeling of the two drugs to warn patients and clinicians, consistent with the precautionary principle of public health.”
In its original petition filed on May 28, 2025, Public Citizen discussed preliminary analyses from the registry, which had consistently shown higher rates of major congenital malformations among exposed fetuses. For example, a 2021 analysis of the registry data found that 13% of 119 live births with prenatal exposure to modafinil or armodafinil had major congenital malformations. The initial petition also outlined evidence from animal studies that led FDA reviewers to conclude that modafinil and armodafinil should be labeled as developmental toxicants, and recommended the establishment of the pregnancy registry.
Additional requests in Public Citizen’s 2025 petition included promptly requiring a warning against the use of modafinil and armodafinil in females of reproductive potential who are not using effective contraceptives. Public Citizen also recommended adding boxed warnings – the most prominent warnings that the FDA can require – on the labeling of both drugs regarding their potential risk of fetal harm.