MHRA safety update on modafinil and congenital malformations

  • Medicines and Healthcare products Regulatory Agency

  • curated by Dawn O'Shea
  • UK Medical News
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The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a drug safety update on the potential risk of congenital malformations with the use of the narcolepsy drug modafinil during pregnancy.

The update follows a European review of the evidence which concluded that there was a possible increased risk of congenital malformations in the children of women treated with modafinil during pregnancy. The review considered data from the prospective, observational US Nuvigil and Provigil 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 product information, including the patient information leaflet, has been updated to reflect this finding.

Interim data ascertained from the 2018 Annual Registry report estimated that the prevalence of major congenital malformations was approximately 14.75 per cent (95% CI, 5.85-23.65%), compared with 3 per cent in the general population. The estimated prevalence of cardiac anomalies of 4.92 per cent (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 nine presented with major 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.

The MHRA says it 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 agency’s advice is that health care professionals should ensure that 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 foetus. Effective contraception is needed during treatment and for two months after stopping treatment. Women of childbearing potential planning a pregnancy should be advised on the need to discuss other narcolepsy treatment options with their doctor before stopping contraception, the safety update states.

Health professionals are also reminded that modafinil may reduce the effectiveness of steroidal contraceptives, including oral contraceptives, therefore alternative or concomitant methods of contraception are required.