其 他 安 全 警 示
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| The United Kingdom: Modafinil (Provigil): increased risk of congenital malformations if used during pregnancy (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that modafinil potentially increases the risk of congenital malformations when used in pregnancy.
A European review concluded that there was a possible increased risk of congenital malformations in the children of women treated with modafinil during pregnancy. The product information, including the patient information leaflet, has been updated.
The review considered data from a prospective United States registry and spontaneous reports of major congenital malformations including congenital heart defects, hypospadias, and orofacial clefts, for which causal relationship with modafinil was considered possible. The MHRA has considered the European review and other safety data, which support the suggestion of an increased risk of major congenital malformations with use of modafinil in pregnancy.
The Nuvigil and Provigil registry, a prospective, observational study in the United States, was established in 2010 to characterise the pregnancy and foetal outcomes associated with exposure to modafinil and related drug armodafinil from 6 weeks before conception and/or during pregnancy.
Interim data ascertained from the 2018 Annual Registry report (considered by the review that led to the most recent changes to product information) estimated that the prevalence of major congenital malformations was approximately 14.75% (95% CI 5.85–23.65), compared with 3% in the general population. The estimated prevalence of cardiac anomalies of 4.92% (0–10.34) was also higher than reported in the general population (1%). These rates are based on prospective data from 78 pregnancy cases; 61 of these reported a live birth outcome, of which 9 presented with major congenital anomalies (including 3 cardiac congenital anomalies). While the target sample size for the registry has not yet been reached, this interim analysis has shown that the prevalence of major congenital malformations is above the background rate in the general population. In addition to the registry findings, studies in animals have shown reproductive toxicity.
Before starting modafinil, women of childbearing potential must be informed of the risk of teratogenicity. Patients must use effective contraception during treatment with modafinil and for 2 months after stopping. Modafinil may reduce the effectiveness of steroidal contraceptives, including oral contraceptives, through the induction of CYP3A4/5. Alternative or concomitant methods of contraception are required.
Advice for healthcare professionals:
- Modafinil potentially increases the risk of congenital malformations (including congenital heart defects, hypospadias, and orofacial clefts); modafinil should not be used in pregnancy and alternative treatment options for narcolepsy should be considered.
- Women of childbearing potential must use effective contraception during treatment and for 2 months after stopping modafinil.
- Modafinil may reduce the effectiveness of steroidal contraceptives, including oral contraceptives, therefore alternative or concomitant methods of contraception are required.
- Ensure all female patients of childbearing potential taking modafinil are informed and fully understand that: modafinil should not be used during pregnancy due to the increased risk to the fetus; effective contraception is needed during treatment with modafinil and for 2 months after stopping modafinil treatment; and they should discuss plans for pregnancy early with their doctor and continue contraception for 2 months after stopping modafinil.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/modafinil-provigil-increased-risk-of-congenital-malformations-if-used-during-pregnancy#history
In Hong Kong, there is no registered pharmaceutical product containing modafinil or armodafinil. Related news was previously issued by Health Canada, and was posted on the Drug Office website on 21 Jun 2019.
Ends/Tuesday, Nov 17, 2020
Issued at HKT 16:00
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