Health Canada, a federal department responsible for helping Canadians maintain and improve their health, issued a letter to health care professionals in June, warning them about the risk of congenital anomalies when modafinil is used during pregnancy. Modafinil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder.
Modafinil Pregnancy Registry
According to the Health Canada letter, after developmental toxicity was observed in animal studies, the U.S. Food and Drug Administration requested the initiation of the Nuvigil/Provigil Pregnancy Registry to characterize the pregnancy and fetal outcomes associated with Provigil (modafinil) and Nuvigil (armodafinil, the R-enantiomer of modafinil; not marketed in Canada) exposure during pregnancy. Teva Canada Innovation informed Health Canada in February 2019 of the results of the 2018 annual report of the ongoing registry. Teva Canada Limited and Teva Canada Innovation are part of Teva Pharmaceutical Industries Ltd., the world’s largest generic drug maker.
Registry Report
Health Canada indicated that this report documented cases of spontaneous abortion and of major congenital anomalies, including cardiac congenital anomalies. The frequency of major congenital anomalies (17.3%) and cardiac anomalies (4%) associated with the exposure to modafinil and/or armodafinil was above the frequency observed in the general population (3% and 1%, respectively). There have also been post-marketing reports of congenital malformations and of low fetal growth, as well as cases of babies who failed to thrive (poor physical development).
Health Canada Actions
Based on these findings, Health Canada updated the Canadian Product Monograph (CPM) to include a contraindication to the use of modafinil in pregnancy. Health Canada recommends that women who are pregnant, or plan to become pregnant, must not use modafinil in order to avoid the risk of birth defects.
Information for Health Care Professionals
Health Canada advises health care professionals to discuss the potential risks to a fetus with all female patients who are treated or to be treated with modafinil. Providers also should ensure that all female patients of reproductive potential have a negative pregnancy test within a week before starting treatment with modafinil and use effective contraception during therapy and for two months after discontinuation.
AASM Response
The AASM has reached out to Teva to gather more information and is contacting the FDA to request additional guidance for health care professionals in the U.S.
Read more clinical sleep medicine news from the AASM.
