SUMMARY: Modafinil is a psychostimulant medication used to improve wakefulness in adults with narcolepsy, for fatigue related to multiple sclerosis, and for the treatment of attention deficit hyperactivity disorder (ADHD). Armodafinil is the R-enantiomer of modafinil and possesses the same pharmacodynamic effects; although this medication is not licensed for clinical use in the UK, some of the available pregnancy data are provided from studies using this medication.
Published data regarding maternal modafinil/armodafinil use in pregnancy are limited, consisting of a small number of uncontrolled case reports/series and two population-based cohort studies. Together these studies describe approximately 290 exposed pregnancies, of which 230 were in the first trimester.
The available data, although limited and conflicting, provide evidence that modafinil/armodafinil use in pregnancy may increase the risk of congenital malformation. Of the three largest studies currently available (each describing <100 first trimester-exposed pregnancies), two identified increased risks, with the controlled study indicating an approximate 3-fold increased risk attributable to modafinil exposure. The remaining study found no increase in the rate of malformation following first trimester modafinil exposure. Due to the limited and conflicting nature of the available evidence, it is currently unclear if first trimester modafinil exposure truly increases the risk of fetal malformation. If the evidence indicating an increased risk of malformation is accurate, the data suggest that approximately 4 to 6 additional malformed infants could be expected for every 100 modafinil-exposed pregnancies (relative to an expected background rate of 2 to 3 per 100). A single uncontrolled study described a rate of miscarriage consistent with the expected background rate following maternal modafinil/armodafinil use in early pregnancy. However, the available data are provided by a single uncontrolled case series and therefore additional studies are required.
No studies have investigated the risk of stillbirth, preterm delivery, growth restriction, neurodevelopmental impairment or neonatal complications following modafinil use in pregnancy. Although the risk of neonatal withdrawal has not been formally studied, as modafinil is a centrally acting medication, symptoms of withdrawal may be experienced following its use in the latter stages of pregnancy.
It is important to ensure that the maternal condition for which modafinil is prescribed is appropriately treated during pregnancy. It is strongly recommended that the potential risks and benefits of continued use, as well as any potential alternatives, are discussed with UKTIS.
Detailed anomaly scans are recommended following first trimester modafinil exposure. The anomalies described in the literature include congenital torticollis, unspecified cardiac defects and hypospadias, which may not always be detectable by prenatal ultrasound. Exposure to modafinil at any stage in pregnancy would not be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.