Summary Safety Review - Oral Retinoid Products - Assessing the Potential Risk of Impotence (erectile dysfunction)

January 10, 2017

Product

Oral retinoid products (isotretinoin, tretinoin, alitretinoin and acitretin)

Potential Safety Issue

Impotence (erectile dysfunction)

Key Messages

• Oral retinoids are a group of prescription drugs authorized for sale in Canada to treat various skin conditions like severe acne, chronic eczema and psoriasis. Tretinoin is also used to treat a type of blood cancer.
• Health Canada reviewed the potential risk of impotence because of an article in the scientific literature suggesting that treatment with isotretinoin can cause this side effect.
• Health Canada’s review of the available information concluded that there may be a link between the use of oral isotretinoin products and the risk of impotence, but could not draw the same conclusion for the other drugs in the class. Health Canada recommended that the product information for all isotretinoin products be made consistent by listing impotence as a side effect.

Overview

Health Canada reviewed the potential risk of impotence (erectile dysfunction) with the use of oral retinoids because of a publication from the Netherlands that linked isotretinoin use with this side effect.^{Footnote 1} Health Canada also reviewed the related evidence regarding all oral retinoids available in Canada. Impotence is when a man cannot achieve or maintain an erect penis for sexual activity.

Use in Canada

• Oral retinoids (in capsules taken by mouth) are prescription drugs authorized for sale in Canada to treat various skin conditions like severe acne, chronic eczema and psoriasis. Tretinoin is also authorized for sale in Canada to treat a type of cancer of the blood (acute promyelocytic leukemia).
• At the time of the review, there were 3 oral isotretinoin-containing products marketed in Canada: Accutane, Clarus, Epuris. The other oral retinoid products include Toctino (alitretinoin), Vesanoid (tretinoin) and Soriatane (acitretin). Oral retinoid products first entered the Canadian market in 1983.
• In 2015 there were over 300 000 prescriptions (new and refills) for oral retinoids in Canada. The most commonly prescribed was isotretinoin with approximately 265 000 prescriptions.

Safety Review Findings

• At the time of the review, Health Canada had received a total of 9 unique Canadian reports^{Footnote a} of impotence with oral isotretinoin use. There were no relevant Canadian reports for the other oral retinoid products. There were no instances that showed with certainty that the use of isotretinoin caused impotence because there were other factors that may have played a role, such as depression.
• The review found 215 international reports of erectile dysfunction where retinoids were used. There were also published cases of oral isotretinoin use leading to impotence.
• A review of the scientific literature showed that there were several animal studies which reported that retinoids may have an effect on the male sex organs (testes). One theory proposed in the scientific literature is that retinoids may have an effect on testes leading to a decrease in testosterone and a decrease in sexual function.
• At the time of the review, erectile dysfunction was specifically mentioned in the product information for Epuris (isotretinoin) and Soriatane (acitretin).
• All oral retinoids mention depression as a side effect in their product information. Depression may contribute to impotence.

Conclusions and Actions

• Health Canada’s review of the available information concluded that there may be a link between the use of oral isotretinoin products and the risk of impotence, but could not draw the same conclusion for the other drugs in the class.
• Health Canada recommended that the product information for all isotretinoin products be made consistent to include this risk by adding erectile dysfunction as a side effect in the product information for Accutane and Clarus, as it already appears in the product information for Epuris.
• Health Canada will continue to monitor safety information involving oral retinoid products, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References