Summary Safety Review - Isotretinoin - Assessing the Potential Risk of Sexual Dysfunction, Including Persistent Sexual Dysfunction After Drug Discontinuation

Isotretinoin-containing products

Sexual dysfunction [including erectile dysfunction (trouble getting and maintaining an erection), vulvovaginal dryness (dryness of the vulva and/or vagina), and reduced libido (low sexual desire)], and persistent sexual dysfunction after drug discontinuation

• Health Canada’s safety review concluded that a link between isotretinoin and the risk of sexual dysfunction, including persistent sexual dysfunction after drug discontinuation, could not be ruled out.

• Health Canada reviewed the potential risk of sexual dysfunction, including persistent sexual dysfunction after drug discontinuation, with the use of isotretinoin, a prescription drug authorized for the treatment of severe forms of acne in patients 12 years of age and older that should be used when other treatments did not work.

• The safety review was triggered by a published report from the United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency (MHRA) on isotretinoin and the risk of sexual dysfunction.

• As a precautionary measure, Health Canada will work with the manufacturers to update and align the product safety information in the Canadian product monograph (CPM) for all isotretinoin-containing products to include the potential risk of sexual dysfunction, including persistent sexual dysfunction after drug discontinuation. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

In 2016, Health Canada completed a safety review on oral retinoids and erectile dysfunction. The review found that there may be a link between the use of oral isotretinoin products and the risk of erectile dysfunction. At the time of the review, the CPM for Epuris already included this risk. The CPMs for the other isotretinoin-containing products that were on the market were subsequently updated to include erectile dysfunction, thereby aligning the product safety information for all isotretinoin products.

In 2023, following the publication of a report by the UK MHRA on the risk of sexual dysfunction with the use of isotretinoin, Health Canada reviewed the potential risk of additional sexual dysfunction-related events, including persistent sexual dysfunction after drug discontinuation. At the time of this review, the CPMs for isotretinoin-containing products were not consistently labelled for these additional events.

Sexual dysfunctions are a group of disorders that can affect a person’s ability to engage in sexual activity. Sexual dysfunction-related events include, but are not limited to, erectile dysfunction, vulvovaginal dryness, and reduced libido.

• Isotretinoin is a prescription drug authorized for sale in Canada for the treatment of severe forms of acne in patients 12 years of age and older that should be used when the acne fails to respond to other treatments.

• Isotretinoin has been marketed in Canada since 1983. It is currently available as an oral capsule under the brand names Accutane Roche, Clarus, Epuris, and Absorica LD. A generic version of isotretinoin is also approved in Canada.

• Approximately 2 million isotretinoin prescriptions were dispensed by Canadian retail pharmacies between August 2017 and July 2023. During this time period there was a slight increase in the number of prescriptions dispensed, peaking in 2021.

• Health Canada reviewed the available information from searches of the Canada Vigilance database^a and the scientific literature.

• Health Canada identified 111 cases (11 Canadian and 100 international) reporting 1 or more events of sexual dysfunction, including persistent sexual dysfunction after drug discontinuation, related to the use of isotretinoin. In just over half of the events, the sexual dysfunction was reported as persisting for months to years following drug discontinuation. The average age was 23 years in cases where age was provided. These cases overall did not include sufficient clinical information, including details on mental health at the time of sexual dysfunction, to definitively determine a link between isotretinoin use and sexual dysfunction. However, given the timing of the events, a link could not be ruled out.

• Health Canada also reviewed 6 articles published in the scientific literature. The level of evidence in these articles was considered limited, but some reported sexual dysfunction with isotretinoin use, including those which continued after drug discontinuation.

• Based on the totality of the evidence reviewed, a link between isotretinoin and sexual dysfunction, including persistent sexual dysfunction after drug discontinuation, could not be ruled out. The evidence reported was primarily for erectile dysfunction, reduced libido, and vulvovaginal dryness.

• Despite the limited available evidence, the young age of the intended population, the number of reported cases, and the significant impact of the adverse events are factors that warrant a precautionary approach for this risk.

• Health Canada’s review of the available information concluded that a link between isotretinoin and the risk of sexual dysfunction, including persistent sexual dysfunction after drug discontinuation, could not be ruled out.

• Health Canada will work with the manufacturers to update and align the CPM for all isotretinoin-containing products to include this potential risk.

• Health Canada will also work with the manufacturers to implement additional measures to inform patients of this potential risk.

• Health Canada will inform healthcare professionals about this update through a Health Product InfoWatch communication.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of isotretinoin, and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving isotretinoin, 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 should new health risks be identified.

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

For additional information, contact the Marketed Health Products Directorate.

1. Canadian reports can be accessed through the Canada Vigilance Online Database.