EMA Strengthens Warnings For Retinoids, Starts Probe Into Omega-3 Fatty Acid Medicines
Executive Summary
Package leaflets and boxed warnings on the outer packaging of retinoid medicines in the EU will need to be updated to strengthen measures for pregnancy prevention. Meanwhile, the European Medicines Agency has started to explore whether omega-3 fatty acid medicines that are used to prevent heart disease and stroke after a heart attack actually work.
The European Medicines Agency has completed its review of retinoid medicines and has confirmed that labeling and other measures for pregnancy prevention need to be strengthened and that awareness must be raised about possible neuropsychiatric risks.
In addition, the agency has begun reviewing the use of omega-3 fatty acid medicines in patients who have had a heart attack after research showed that these oral products might not prevent the recurrence of heart disease or stroke as intended.
Package leaflets and boxed warnings on the outer packaging of retinoid medicines will need to convey that these products, used mainly to treat skin conditions such as severe acne, are harmful to an unborn baby if taken during pregnancy, the EMA said.
They will need to state that oral retinoids must not be used during pregnancy. In addition, the oral retinoids acitretin, alitretinoin and isotretinoin must not be taken by women who are able to have children unless the conditions of a new pregnancy prevention program are met, the agency said.
The review of retinoids was initiated by the EMA’s Pharmacovigilance Risk Assessment Committee in July 2016 at the request of the UK. The PRAC assessed the available data on teratogenicity and neuropsychiatric disorders with retinoid medicines, and its recommendations were adopted by the agency’s main scientific committee, the CHMP, last week.
The EMA warned that there may be a possible risk of conditions such as depression and anxiety and mood changes in patients taking oral retinoids. “The limitations of the available data did not allow to clearly establish whether this risk was due to the use of retinoids,” it said. “However, considering that patients with severe skin conditions may be more vulnerable to neuropsychiatric disorders due to the nature of the disease, the prescribing information for oral retinoids will be updated to include a warning about this possible risk.” Warnings will be included in the package leaflet of oral retinoids, as will signs and symptoms that patients and their families should look out for.
As for topical retinoids, the EMA said that while these were less likely to harm the unborn child, as a precaution they also must not be used during pregnancy or by women planning to have a baby. No additional warnings about neuropsychiatric disorders will need to be added to the prescribing information though, because the “available data suggest that topical retinoids do not carry a risk of neuropsychiatric side effects,” the agency said.
Some of the retinoids affected by the review – acitretin, adapalene, alitretinoin, isotretinoin, tazarotene and tretinoin – have been authorized nationally in a number of member states. Alitretinoin has also been authorized centrally as Panretin for the treatment of skin lesions in AIDS patients with the skin cancer, Kaposi’s sarcoma. Another retinoid, bexarotene, has also been authorized centrally, as Targretin, for the treatment of cutaneous T-cell lymphoma. Eisai is the marketing authorization holder for both centrally authorized products.
The CHMP’s opinion regarding retinoids is being forwarded to the European Commission, which will issue a legally binding decision applicable in all EU member states in due course.
Do Omega-3 Fatty Acid Medicines Work?
The EMA’s decision to start reviewing the use of omega-3 fatty acid medicines in patients who have had a heart attack was also announced last week.
Omega-3 fatty acid medicines are used in most EU countries to prevent heart disease and stroke after a heart attack, in combination with other medicines. However, the EMA said that a recent analysis of 10 studies in around 78,000 patients found that adding omega 3-fatty acid medicines to standard treatment did not significantly reduce heart attacks, stroke or other heart and circulatory problems. “These findings were similar to those from other studies published in 2012, which also found no significant reduction in heart disease.”
The EMA noted that the data available when these products were approved showed some benefits in reducing heart attacks, stroke and deaths, although the benefits were considered small.
The review, which will be conducted by the CHMP, was requested by the Swedish medicines agency. It began on March 22, and the CHMP’s opinion will be forwarded to the commission for a legally binding decision
From the editors of Scrip Regulatory Affairs.