New research raises questions about the potential pregnancy side effects of Provigil for unborn children, indicating that use of the narcolepsy drug during the first trimester of pregnancy may increase the risk of congenital malformations.
In findings outlined last week in a research letter published in the Journal of the American Medical Association (JAMA), researchers from Denmark indicate that postmarketing surveillance detected major malformations and birth defects from Provigil pregnancy use. The study came as a result of an alert issued by the drug maker Teva last summer.
According to data provided by Teva, major malformations were seen among 15% of the children exposed to Provigil (modafinil) during pregnancy, compared to only 3% among the general population. The drug maker announced the findings in a Dear Healthcare Professionals letter (PDF) issued on June 7, 2019.
Provigil (modafinil) is a stimulant that was first approved in the U.S. in 1998 for the treatment of daytime sleepiness associated with narcolepsy. It is also frequently used off-label for the treatment of fatigue due to multiple sclerosis.
In this latest study, researchers looked at data on all pregnancies from 2004 through 2017 using the Danish national health registries, to see if they could confirm Teva’s findings. The results indicate that there were at least 49 pregnancies where the mother took Provigil during the first trimester, out of more than 800,000 pregnancies total.
Six of those pregnancies resulted in major congenital malformations, for a Provigil birth defect rate of 12%. That compares to a 3.9% rate of malformations among women who were not exposed. The researchers also looked at mothers who had taken Ritalin (methylphenidate), another stimulant used to treat narcolepsy and attention deficit disorder (ADD) and found a malformation rate of 4.5%.
“In this nationwide study, first-trimester in utero exposure to modafinil compared with methylphenidate or no medication was significantly associated with an increased risk of congenital malformations,” the researchers concluded. “Although further research is needed,women contemplating pregnancy should currently avoid or discontinue modafinil.”
In its Dear Healthcare Professionals letter, Teva also urged women not to use Provigil during pregnancy, and said women of childbearing potential should use effective contraception during Provigil treatment and for two months after stopping its use.