The FDA Must Require Contraindicating the Use of Two Commonly Prescribed Stimulants During Pregnancy
Modafinil and armodafinil can cause major fetal malformations
WASHINGTON, D.C. — The Food and Drug Administration (FDA) must require contraindicating the use of modafinil (Provigil and generics) and armodafinil (Nuvigil and generics) during pregnancy, both of which can cause major fetal malformations, Public Citizen urged today in a petition to the agency.
The FDA approved modafinil and armodafinil to diminish sleepiness in adults with shift work disorders and those with narcolepsy or obstructive sleep apnea. These drugs also are commonly taken for many unapproved uses, including treating symptoms of attention-deficit hyperactivity disorder, chronic fatigue, multiple sclerosis and Parkinson’s disease. The current U.S. labels on both drugs fail to contraindicate the use of these drugs during pregnancy.
Public Citizen’s petition stresses that the contraindication should also include females who can become pregnant and are using hormonal contraceptives, because modafinil and armodafinil can reduce the effectiveness of these contraceptives. Additionally, the FDA should require boxed (prominent) warnings in the labels of both drugs to highlight their risk of embryofetal toxicity.
“Fetal developmental toxicity and death due to modafinil and armodafinil exposure during pregnancy occurred at clinically relevant doses in animal studies,” said Azza AbuDagga, Ph.D., health services researcher at Public Citizen’s Health Research Group. “This likely explains the increased prevalence of congenital malformations in the interim results of the U.S pregnancy registry. FDA action to protect U.S. babies of modafinil and armodafinil users from harm is unacceptably long overdue. As early as 2019, regulatory agencies in other countries (including Australia, Canada, Ireland, and the United Kingdom) have contraindicated the use of these drugs during pregnancy. The FDA cannot afford any further delay in doing the same to warn patients and clinicians, following the precautionary principle of public health.”
“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,” added AbuDagga.
Data from an FDA-mandated U.S. registry, called the Nuvigil and Provigil Pregnancy Registry, found a higher prevalence of major congenital malformations among babies born to female users of modafinil or armodafinil than that in the general U.S. population:
- A 2018 interim report of the pregnancy registry submitted to the U.K.’s Medicines and Healthcare Products Regulatory Agency indicated the estimated prevalence of major congenital malformations was approximately 15% among babies of modafinil or armodafinil users, compared with just 3% among the general U.S. population. The estimated prevalence of heart anomalies among live births exposed to the drugs in utero was approximately 5%, compared with 1% in the general U.S. population.
- A 2021 industry-funded data analysis from the same registry found that 13% and 3% of 119 pregnancies with live births (that had known fetal outcomes) had major congenital malformations (including congenital torticollis and hypospadias) as well as heart malformations, respectively.