Modafinil and Armodafinil Throughout Being pregnant Related to Elevated Threat of Malformations

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Modafinil (model title Provigil) and armodafinil (Nuvigil) are wake-promoting brokers used to deal with sleepiness as a consequence of narcolepsy, shift work sleep problem, or obstructive sleep apnea. They’re additionally utilized in different settings, usually together with different medicines, to deal with ADHD signs, depressive signs, fatigue, and cognitive dysfunction.  

Danish Examine of fifty Modafinil-Uncovered Infants

In 2020, a Danish research reported a serious malformation charge of 12% (n = 6) in 50 modafinil-exposed pregnancies, in comparison with a charge of 4.5% in methylphenidate-exposed pregnancies and three.9% in unexposed pregnancies. After adjusting for potential confounders, modafinil was related to a considerably elevated danger for malformation in comparison with methylphenidate or no publicity.

Information from the Swedish and Norwegian Examine of 133 Modafinil-Uncovered Infants

Researchers have used Swedish and Norwegian delivery registers to establish ladies utilizing modafinil in being pregnant.  All singleton pregnancies leading to dwell births have been recognized within the nationwide medical delivery registers from Norway (2005- 2017) and Sweden (2006-2016).  

On this cohort of almost 2 million pregnancies, researchers used nationwide prescribed drug registries to establish 133 pregnancies uncovered to modafinil throughout early being pregnant. In comparison with pregnant ladies who had not obtained modafinil, pregnant ladies utilizing modafinil have been extra prone to be chubby or overweight, had greater charges of smoking, and have been extra prone to be identified with narcolepsy, a number of sclerosis, or ADHD.

Total, the speed of main malformations within the unexposed group was 2.1%.  Within the modafinil group, there have been three infants identified with a serious malformation, leading to a prevalence charge of two.6% and a crude danger ratio of 1.06 (95% CI, 0.35-3.26). 

Information from the Provigil/Nuvigil Being pregnant Registry

The US Provigil/Nuvigil Being pregnant Registry was established in February 2010 and has collected information from ladies uncovered to modafinil and/or armodafinil inside 6 weeks previous to conception or throughout being pregnant.  Collected data is classed as potential if enrollment happens earlier than data of the being pregnant end result or detection of a congenital malformation via prenatal testing.  

In distinction to hostile occasions reporting carried out by drug producers which might overestimate the prevalence of malformations, these information have been collected as a part of a being pregnant registry which recruited pregnant sufferers previous to the detection of a congenital malformation. In 2018, preliminary information from the registry launched information indicating a prevalence of 15% for main malformations in infants uncovered to modafinil throughout being pregnant.  After these findings have been launched, regulatory our bodies in a number of nations issued warnings concerning the usage of modafinil in ladies of reproductive age.

In the latest report from the registry, researchers analyzed information from 148 pregnancies uncovered to modafinil (Provigil) or armodafinil (Nuvigil) which have been prospectively adopted (n = 122) or retrospectively ascertained (n = 26).  On this cohort, 81 ladies obtained modafinil, 67 obtained armodafinil, and one affected person obtained each medicine. Narcolepsy was indicated in 70% of prescriptions.  

Amongst  the 97 potential dwell births with first trimester publicity, 13% (n = 13) had main malformations, which is properly above the prevalence of about 3%-4% noticed within the basic inhabitants.  Of those dwell births with malformations, 4 had congenital torticollis, 2 had hypospadias, and three had congenital coronary heart defects.  Including within the retrospective circumstances didn’t change the prevalence of malformations.  

These findings are just like these noticed within the Danish research revealed in 2020 which demonstrated a serious malformation charge of 12% (n = 6) in 49 modafinil-exposed pregnancies.  Nevertheless, these information and the present research should not per a more moderen report from Sweden and Norway, which demonstrated an general danger of main malformations of two.3% (3 out of 133 uncovered pregnancies).  There may be not a selected sample of malformations related to publicity to modafinil, though it’s notable that 4 of the 13 infants within the present research had congenital torticollis.  The sort of malformation is comparatively uncommon within the basic inhabitants and is a malformation not sometimes reported in these publicity research.  

Advising Sufferers on the Use of Modafinil Throughout Being pregnant

Primarily based on these findings, we’d not suggest the usage of modafinil or armodafinil throughout being pregnant.  Ideally we want to have information from 600-700 exposures to get a greater estimate of danger; basing choices concerning security on small pattern sizes can result in miscalculations of danger in both route.  Nonetheless, within the absence of ample information, it will be clever to train warning when utilizing modafinil and armodafinil in ladies of reproductive age, provided that half of all pregnancies are unplanned. In these conditions the place the usage of modafinil is indicated in a lady of reproductive age, efficient contraception is important.

Vital Reminder: Modafinil and armodafinil are inducers of the CYP-3A4 hepatic enzymes and improve the metabolism of hormonal contraceptives, thus they might lower the effectiveness of hormonal contraception, together with contraception capsules, injections, implants, transdermal patches, and vaginal rings.   Ladies who plan to take modafinil or armodafinil ought to be recommended to make use of an alternate, more practical, technique of contraception, equivalent to a barrier technique or an IUD.

Well being Canada has issued the next suggestions concerning the usage of modafinil.     

  • Ladies who’re pregnant, or plan to grow to be pregnant, shouldn’t use modafinil.
  • As a result of hormonal contraception strategies, equivalent to contraception capsules, could not work as properly when used similtaneously modafinil, ladies utilizing some of these contraception could have a better probability of getting pregnant whereas taking modafinil. Different modes of contraception ought to be thought-about.  
  • Ladies ought to take a being pregnant check inside every week earlier than beginning remedy with modafinil to make sure they aren’t pregnant.

Ruta Nonacs, MD PhD

Cesta CE, Engeland A, Karlsson P, Kieler H, Reutfors J, Furu Ok.  Incidence of Malformations After Early Being pregnant Publicity to Modafinil in Sweden and Norway. JAMA. 2020 Sep 1;324(9):895-897.

Damkier P, Broe A.  First-Trimester Being pregnant Publicity to Modafinil and Threat of Congenital Malformations.  JAMA Psychiatry, January 2020.

Kaplan S, Braverman DL, Frishman I, Bartov N.  Being pregnant and Fetal Outcomes Following Publicity to Modafinil and Armodafinil Throughout Being pregnant.  JAMA Intern Med. 2020 Oct 19.

ALERTEC (modafinil) and the Threat of Congenital Anomalies (Well being Canada)

US Provigil/Nuvigil Being pregnant Registry

Kaplan S, Braverman DL, Frishman I, Bartov N.  Being pregnant and Fetal Outcomes Following Publicity to Modafinil and Armodafinil Throughout Being pregnant.  JAMA Intern Med. 2020 Oct 19.

ALERTEC (modafinil) and the Threat of Congenital Anomalies (Well being Canada)

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