New Public Citizen Filing Reiterates Need to Warn About Fetal Harm of Modafinil, Armodafinil

On May 18, 2026, Public Citizen and Public Citizen’s Health Research Group submitted a supplemental petition to the Food and Drug Administration (FDA) urging the agency to promptly require an explicit warning against using two widely prescribed oral wakefulness-promoting drugs during pregnancy: modafinil (PROVIGIL and generics) and armodafinil (NUVIGIL and generics).[1]

The filing is based on the final analysis of 14 years of data from an FDA-mandated U.S. registry,[2] called the Nuvigil and Provigil Pregnancy Registry, which strengthens a May 2025 petition that we submitted to the agency.[3],[4] This analysis demonstrates a fourfold higher rate of major congenital malformations among fetuses exposed during pregnancy to modafinil or armodafinil than in the general U.S. population. It was published in the Dec. 2025 issue of Neurology: Clinical Practice and funded by Teva, the former manufacturer of Provigil and Nuvigil.

Yet, as of early June 2026, the registry findings had not been incorporated into the U.S. labeling of the two drugs.[5],[6] Instead, the current modafinil labeling continues to indicate that the drug “should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus” and armodafinil’s medication guide continues to state that “[i]t is not known if [the drug] will harm [the] unborn baby.”[7] The labeling for both drugs indicates only that, based on animal data, the drugs may cause fetal harm.

About modafinil and armodafinil

In 1998 and 2007, respectively, the FDA approved the centrally acting, structurally similar drugs modafinil and armodafinil to improve wakefulness in adults with excessive sleepiness associated with narcolepsy (a rare sleep disorder characterized by excessive daytime sleepiness and brief involuntary sleep episodes).

Subsequently, the FDA extended the approved wakefulness-promoting uses of modafinil and armodafinil to include adults with obstructive sleep apnea (blockage of the upper airway during sleep) and shift work disorder (excessive sleepiness or insomnia in people who work shifts or irregular schedules during the typical sleep period).

Both drugs also are commonly used for unapproved (off-label) uses, such as treating symptoms of attention-deficit hyperactivity disorder, chronic fatigue, jet lag, multiple sclerosis and Parkinson’s disease.

Our original petition

Our 2025 petition urged the FDA to require a warning in the labeling of modafinil and armodafinil to contraindicate their use in women who are pregnant or planning to become pregnant. The warning also applies to females who are relying on hormonal contraceptives as their sole method of birth control, because the two drugs decrease the effectiveness of such contraceptives.

Moreover, we asked the FDA to mandate boxed warnings (the most prominent warnings the agency can require) to highlight the potential risk of embryofetal toxicity in the labeling of both drugs.

Our petition was based on animal studies and post-marketing observational studies, including interim analyses of the U.S. registry.

For example, an FDA-required post-marketing animal study examining exposure to modafinil in pregnant rabbits linked the drug to increased rates of resorption (disintegration) in exposed fetuses, fetal alterations (including skeletal malformations and abnormal variations), a reduced number of live fetuses and decreased fetal body weight.

Similarly, a preapproval study involving the use of armodafinil in pregnant rats linked the drug to a slight but statistically significant increase in fetal resorption and reduced body weight. Moreover, this study found abnormal alterations in exposed fetuses, including dilation of the kidney and certain reduced bone ossification.

Since fetal harm in the animal studies occurred at clinically relevant doses, FDA reviewers recommended establishing the U.S. pregnancy registry for the two drugs.[8],[9]

Various interim analyses of the post-marketing U.S. registry documented higher rates of major congenital malformations among infants exposed to either of the two drugs during pregnancy. For example, a 2021 industry-funded analysis found that 13% of 119 live births with prenatal exposure to modafinil or armodafinil involved major congenital malformations, compared with just 3% in the general U.S. population.[10] Moreover, the rate of heart malformations among exposed live births was approximately 3%, compared with 1% in the general U.S. population.

The malformations included torticollis (a condition with contracted neck muscles that twist the head to one side) and hypospadias (a congenital condition characterized by an abnormal location of the urethral opening in males).

Our original petition highlighted that the above evidence has already led regulators in several countries — including Australia,[11],[12] Canada,[13] Ireland[14] and the United Kingdom[15] — to require warnings against the use of modafinil and armodafinil during pregnancy and in females who may become pregnant and are not using effective contraceptives.

Final registry analysis

From February 2010 to January 2024, a total of 191 pregnancies were enrolled in the U.S. registry.[16] These pregnancies were associated with the use of modafinil (49%), armodafinil (48%), both drugs (2%) or an undetermined one of these drugs (1%) during pregnancy or within six weeks prior to pregnancy. Enrollment was voluntary and initiated by the participants. The mean age of the participants was 31 years. The most common reasons for taking the medications were to treat narcolepsy and idiopathic hypersomnia, a chronic sleep condition with unknown cause characterized by severe, uncontrollable daytime sleepiness despite normal sleep duration.

Pregnancy and fetal outcomes were known for 179 pregnancies, which resulted in 188 fetuses. Of those fetuses, 156 (83%) were prospective (enrolled in the registry before the pregnancy outcome was known or a congenital malformation was detected through prenatal testing), and the remaining 32 (17%) were retrospective (enrolled after either the pregnancy outcome or congenital malformation was known).

The 156 prospectively enrolled fetuses included 137 (88%) live births, 17 (11%) spontaneous abortions and 2 (1%) elective pregnancy terminations. The median gestational age for spontaneous abortions was 9 weeks.

Of the 156 prospectively enrolled fetuses exposed to modafinil or armodafinil during pregnancy, 13% had major congenital malformations, a rate much higher than that of the general population. The malformations involved the musculoskeletal system, central nervous system, male genitalia, heart, cleft lip or palate and other structural abnormalities, with some involving chromosomal anomalies.

Likewise, of the 137 prospective live-birth fetuses exposed to modafinil or armodafinil at any time during pregnancy, 13% had major congenital malformations; the rate was 14% among those exposed during the first trimester. Moreover, 17% of the prospective live-birth fetuses had at least one minor birth defect.

The U.S. registry is one of the largest available prospective data sources on exposure to modafinil or armodafinil during pregnancy, and analyses of its data have consistently demonstrated an increased risk of major congenital malformations associated with prenatal exposure to these drugs.

Therefore, our supplemental petition emphasized that the FDA cannot afford any further delay in following the public health precautionary principle by warning patients and clinicians about the potential risk of major congenital malformations associated with the use of modafinil and armodafinil during pregnancy.

This is especially important given the severity of these congenital malformations, the extensive off-label use of modafinil and armodafinil and the fact that nearly half of U.S. pregnancies are unplanned.[17]

What You Can Do

Do not use either modafinil or armodafinil if you are currently pregnant, planning to become pregnant or using hormonal contraceptives as your sole contraceptive method.

If you can become pregnant and need treatment with modafinil or armodafinil, consult your clinician to rule out pregnancy before initiating treatment with these drugs and use effective contraceptives during treatment and for two months after discontinuing these drugs.[18] For example, if you use a hormonal contraceptive, use an added barrier method or a nonhormonal contraceptive.

Because of their potentially serious adverse effects (including skin rashes), risk of abuse and other risks, we do not recommend the use of modafinil or armodafinil for any reason except managing narcolepsy symptoms, as advised by the European Medicines Agency.[19]
 

References

[1] Public Citizen. Supplemental petition to the FDA to require a pregnancy contraindication for modafinil and armodafinil. May 18, 2026. https://www.citizen.org/article/supplemental-petition-to-the-fda-to-require-a-pregnancy-contraindication-for-modafinil-and-armodafinil/.  Accessed May 29, 2026.

[2] Kaplan S, Carneal-Frazer N, Braverman DL, et al. Pregnancy and fetal outcomes following prenatal exposure to modafinil and/or armodafinil: A 14-year registry study. Neurol Clin Pr. 2025;15(6):e200551.

[3] Public Citizen petitions the FDA to contraindicate use of two wakefulness-promoting drugs during pregnancy. Worst Pills, Best Pills News. September 2025. https://www.worstpills.org/newsletters/view/1681. Accessed May 4, 2026.

[4] Public Citizen. FDA Petition to require contraindicating use of modafinil (PROVIGIL and generics) and armodafinil (NUVIGIL) during pregnancy. May 28, 2025. https://www.citizen.org/article/fda-petition-to-require-contraindicating-use-of-modafinil-provigil-and-generics-and-armodafinil-nuvigil-during-pregnancy/. Accessed May 4, 2026.

[5] Apotex Corp. U.S. label: modafinil (PROVIGIL). February 2025. https://www.provigil.com/pdf/provigil-prescribing-information.pdf. Accessed May 4, 2026.

[6] Apotex Corp. U.S. label: armodafinil (NUVIGIL). February 2025. https://www.nuvigil.com/pdf/nuvigil-prescribing-information.pdf. Accessed May 4, 2026.

[7] Apotex Corp. U.S. medication guide: armodafinil (NUVIGIL). February 2025. https://www.nuvigil.com/pdf/nuvigil-medication-guide.pdf. Accessed May 4, 2026.

[8] Food and Drug Administration. Medical review, Part 1, NDA 21-875, armodafinil (Nuvigil). June 2, 2007. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021875s000_MedR_P1.pdf. Accessed May 4, 2026.

[9] Food and Drug Administration. Review and evaluation of pharmacology and toxicology (by J. Edward Fisher, Ph.D. et al.), armodafinil (Nuvigil), NDA: 21-875. April 28, 2006. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021875s000_PharmR.pdf. Accessed May 4, 2026.

[10] Kaplan S, Braverman DL, Frishman I, Bartov N. Pregnancy and fetal outcomes following exposure to modafinil and armodafinil during pregnancy. JAMA Intern Med. 2021;181(2):275-277.

[11] Arrotex Pharmaceuticals. Australian label: Modafinil (APO-MODAFINIL). September 2025. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-PI-01696-1&d=20260415172310101. Accessed May 4, 2026.

[12] Arrotex Pharmaceuticals. Australian label: armodafinil (NUVIGIL). April 2026. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2026-PI-01403-1&d=20260415172310101. Accessed May 4, 2026.

[13] Teva Canada. Canadian label: Modafinil (ALERTEC). July 2023. https://pdf.hres.ca/dpd_pm/00071543.PDF. Accessed May 4, 2026.

[14] Bluefish Pharmaceuticals. Irish label: modafinil. September 2022. https://assets.hpra.ie/products/Human/19717/Licence_PA1436-031-002_08092022120619.pdf. Accessed May 4, 2026.

[15] Teva Pharma B.V. U.K. label: modafinil (PROVIGIL). June 2021. https://www.medicines.org.uk/emc/product/5412/smpc/print. Accessed May 4, 2026.

[16] Kaplan S, Carneal-Frazer N, Braverman DL, et al. Pregnancy and fetal outcomes following prenatal exposure to modafinil and/or armodafinil: A 14-year registry study. Neurol Clin Pr. 2025;15(6):e200551.

[17] Rossen LM, Hamilton BE, Abma JC, et al. Updated methodology to estimate overall and unintended pregnancy rates in the United States. National Center for Health Statistics. Vital Health Stat 2(201). 2023. https://www.cdc.gov/nchs/data/series/sr_02/sr02-201.pdf. Accessed May 4, 2026.

[18] Arrotex Pharmaceuticals. Australian label: Modafinil (APO-MODAFINIL). September 2025. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-PI-01696-1&d=20260415172310101. Accessed May 4, 2026.

[19] European Medicines Agency. European Medicines Agency recommends restricting the use of modafinil. July 22, 2010. https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-restricting-use-modafinil. Accessed May 4, 2026.