Modafinil (model title Provigil) and armodafinil (Nuvigil) are wake-promoting brokers used to deal with sleepiness resulting from narcolepsy, shift work sleep problem, or obstructive sleep apnea. They’re additionally utilized in different settings, usually together with different drugs, to deal with ADHD signs, depressive signs, fatigue, and cognitive dysfunction.
Danish Research of fifty Modafinil-Uncovered Infants
In 2020, a Danish study 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 Research of 133 Modafinil-Uncovered Infants
Researchers have used Swedish and Norwegian birth registers to determine girls utilizing modafinil in being pregnant. All singleton pregnancies leading to stay births had been recognized within the nationwide medical start registers from Norway (2005- 2017) and Sweden (2006-2016).
On this cohort of almost 2 million pregnancies, researchers used nationwide prescribed drug registries to determine 133 pregnancies uncovered to modafinil throughout early being pregnant. In comparison with pregnant girls who had not acquired modafinil, pregnant girls utilizing modafinil had been extra more likely to be obese or overweight, had greater charges of smoking, and had been extra more likely to be recognized 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 recognized 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 Pregnancy Registry was established in February 2010 and has collected knowledge from girls uncovered to modafinil and/or armodafinil inside 6 weeks previous to conception or throughout being pregnant. Collected info is classed as potential if enrollment happens earlier than information of the being pregnant consequence or detection of a congenital malformation by means of prenatal testing.
In distinction to adversarial occasions reporting carried out by drug producers which might overestimate the prevalence of malformations, these knowledge had 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 knowledge from the registry launched knowledge indicating a prevalence of 15% for main malformations in infants uncovered to modafinil throughout being pregnant. After these findings had been launched, regulatory bodies in several countries issued warnings concerning using modafinil in girls of reproductive age.
In the most recent report from the registry, researchers analyzed knowledge from 148 pregnancies uncovered to modafinil (Provigil) or armodafinil (Nuvigil) which had been prospectively adopted (n = 122) or retrospectively ascertained (n = 26). On this cohort, 81 girls acquired modafinil, 67 acquired armodafinil, and one affected person acquired each medication. Narcolepsy was indicated in 70% of prescriptions.
Amongst the 97 potential stay births with first trimester publicity, 13% (n = 13) had main malformations, which is nicely above the prevalence of about 3%-4% noticed within the common inhabitants. Of those stay 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 study printed in 2020 which demonstrated a serious malformation charge of 12% (n = 6) in 49 modafinil-exposed pregnancies. Nevertheless, these knowledge and the present research are usually not in line with a newer report from Sweden and Norway, which demonstrated an total danger of main malformations of two.3% (3 out of 133 uncovered pregnancies). There’s 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 common inhabitants and is a malformation not usually reported in these publicity research.
Advising Sufferers on the Use of Modafinil Throughout Being pregnant
Primarily based on these findings, we’d not suggest using modafinil or armodafinil throughout being pregnant. Ideally we want to have knowledge from 600-700 exposures to get a greater estimate of danger; basing selections concerning security on small pattern sizes can result in miscalculations of danger in both path. Nonetheless, within the absence of ample knowledge, it might be sensible to train warning when utilizing modafinil and armodafinil in girls of reproductive age, on condition that half of all pregnancies are unplanned. In these conditions the place using modafinil is indicated in a girl of reproductive age, efficient contraception is important.
Necessary Reminder: Modafinil and armodafinil are inducers of the CYP-3A4 hepatic enzymes and enhance 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. Girls who plan to take modafinil or armodafinil needs to be endorsed to make use of an alternate, more practical, methodology of contraception, resembling a barrier methodology or an IUD.
Health Canada has issued the next suggestions concerning using modafinil.
- Girls who’re pregnant, or plan to turn into pregnant, shouldn’t use modafinil.
- As a result of hormonal contraception strategies, resembling contraception capsules, could not work as nicely when used similtaneously modafinil, girls utilizing all these contraception could have a better likelihood of getting pregnant whereas taking modafinil. Different modes of contraception needs to be thought-about.
- Girls ought to take a being pregnant take a look at inside every week earlier than beginning therapy with modafinil to make sure they don’t seem to be pregnant.
Ruta Nonacs, MD PhD
Cesta CE, Engeland A, Karlsson P, Kieler H, Reutfors J, Furu Okay. Incidence of Malformations After Early Pregnancy Exposure to Modafinil in Sweden and Norway. JAMA. 2020 Sep 1;324(9):895-897.
Damkier P, Broe A. First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations. JAMA Psychiatry, January 2020.
Kaplan S, Braverman DL, Frishman I, Bartov N. Pregnancy and Fetal Outcomes Following Exposure to Modafinil and Armodafinil During Pregnancy. JAMA Intern Med. 2020 Oct 19.
ALERTEC (modafinil) and the Risk of Congenital Anomalies (Well being Canada)
US Provigil/Nuvigil Pregnancy Registry
Kaplan S, Braverman DL, Frishman I, Bartov N. Pregnancy and Fetal Outcomes Following Exposure to Modafinil and Armodafinil During Pregnancy. JAMA Intern Med. 2020 Oct 19.
ALERTEC (modafinil) and the Risk of Congenital Anomalies (Well being Canada)
