New safety warnings for isotretinoin (Roaccutane)

Summary

Isotretinoin, originally sold as Roaccutane, is a prescription medicine used to treat patients with severe cystic acne who have not seen improvement after conventional therapy, including systemic antibiotics.

Additional safety information will be added to all isotretinoin products, further highlighting the recognised potential risks of mood-related changes and sexual disorders. The update includes:

• new advice to conduct a mental health assessment for all patients before starting isotretinoin
• what to do if mood-related changes develop
• new warnings and advice added regarding sexual health-related side effects.

This safety update follows a TGA safety investigation conducted in 2024 after international regulators strengthened warning about psychiatric and sexual disorders for isotretinoin. As a result, the Product Information (PI) and Consumer Medicine Information (CMI) are being updated as a precautionary measure and to align with international regulatory advice.

What health professionals should do

Health professionals should be alert to the potential psychiatric and sexual disorders associated with isotretinoin. These side effects can result in serious consequences, especially considering that isotretinoin is often used in adolescents.

You should be alert to patients who show signs of:

• depression
• psychotic behaviours
• suicidal thoughts and actions (rare)
• sexual dysfunction, including erectile dysfunction
• decreased sex drive (libido)
• vulvovaginal dryness
• feeling numb or indifferent (anhedonia)
• enlarged breasts in males (gynaecomastia).

Before initiating isotretinoin, prescribers are advised to assess patients’ mental health as well as their family history of mental health conditions.

Health professionals should monitor for depression and sexual disorders both before and during treatment. If these symptoms occur, cease treatment immediately. It is possible that discontinuation of treatment may not alleviate symptoms and further specialist evaluation may be necessary.

There is a range of generic isotretinoin products on the market, subsidised by the Pharmaceutical Benefits Scheme as “authority required (streamlined)” with different requirements in various jurisdictions. All generics will be required to align their PI and CMI documents with Roaccutane.

Background

According to the Australasian College of Dermatologists, patients with acne may suffer from poor body image, low self-esteem, experience social isolation and avoid participating in daily activities, which persist long after the active lesions have disappeared. Increased levels of anxiety, anger, depression, and frustration are also observed among patients with acne, often a result of the emotional impact. The college advises that isotretinoin is effective in treating mild-moderate, severe, persistent and/or scarring acne. The college updated its position statement on the use of isotretinoin for the treatment of acne in October 2024.

We initially investigated the association between isotretinoin and psychiatric adverse reactions in 2016, concluding that the then-current warnings in the Australian PI were appropriate. We published an MSU to remind prescribers of the risks and the need for careful psychological assessment prior to and during isotretinoin treatment.

The UK Commission on Human Medicines Isotretinoin Expert Working Group published a report on isotretinoin and the risk of psychiatric and sexual disorders in April 2023. Health Canada published a summary safety review in June 2024 regarding isotretinoin and the potential risk of sexual dysfunction, including persistent sexual dysfunction after drug discontinuation.

We undertook an investigation to review all current information on these safety signals. The investigation concluded that an association between isotretinoin and psychiatric/sexual disorders could not be ruled out. Given the reported cases of severe and sometimes persisting adverse events and that isotretinoin is commonly used to treat severe cystic acne in adolescent populations, it was recommended the PI be updated as a precautionary measure and to align with international regulators.

Adverse events reported to us

A search of our publicly available Database of Adverse Event Notification (DAEN) on 28 January 2025 identified 117 cases of psychiatric adverse event associated with isotretinoin identified by the reporter as serious. Reported adverse events in these cases include: depression (48 cases), suicidal ideation (28 cases), completed suicide (26 cases) suicide attempt (18 cases), psychotic disorder (15 cases) and anxiety (14 cases). Some reports may include more than one of these adverse events.

There are also 24 reports of sexual dysfunction-related adverse events, including: erectile dysfunction (5 cases) reduced sense of touch (hypoaesthesia) (4 cases), vulvovaginal dryness (3 cases), libido decreased (2 cases), loss of libido (2 cases) and sexual dysfunction (2 cases).

It is important to note that inclusion in the DAEN does not mean that the details of the reported event have been confirmed, or that the event has been determined to be related to a medicine.

Updates to the PI

Changes to the isotretinoin PI are highlighted below (Roaccutane is used as the example and all other products will be required to align with this text).

Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Psychiatric Disorders

Depression, psychotic symptoms, and, rarely, suicide, suicidal ideation and attempts have been reported with Roaccutane. All patients should have an assessment of their mental health, and of family history of mental health conditions, before starting treatment with Roaccutane.  Particular care needs to be taken in patients with a history of depression and all patients should be monitored for signs of depression. If symptoms of depression develop or worsen, the drug should be discontinued promptly and the patient referred for appropriate psychiatric treatment. Although no mechanism of action for these events has been established, discontinuation of Roaccutane may not alleviate symptoms and therefore further psychiatric or psychological evaluation may be necessary.

Sexual Disorders

Erectile dysfunction, decreased libido, vulvovaginal dryness, anhedonia and gynaecomastia have been reported with Roaccutane. Patients should be asked about signs or symptoms of sexual dysfunction prior to starting therapy, and monitored for development of new sexual disorders during treatment. Although no mechanism of action for these events has been established, discontinuation of Roaccutane may not alleviate symptoms and therefore further specialist evaluation may be necessary. 

Section 4.8 ADVERSE EFFECTS (UNDESIRABLE EFFECTS)

Post-marketing experience

Reproductive system and breast disorders

Sexual dysfunction including erectile dysfunction, and decreased libido, vulvovaginal dryness, anhedonia and gynaecomastia. A causal association with these adverse effects has not been established.

Further reading

• Therapeutic Goods Administration. Medicines Safety Update Volume 7, Number 4, August 2016.
• Medicines and Healthcare products Regulatory Agency Commission on Human Medicines. Report of the Commission on Human Medicines Isotretinoin Expert Working Group. 26 April 2023.
• Health Canada. Summary Safety Review - Isotretinoin - Assessing the Potential Risk of Sexual Dysfunction, Including Persistent Sexual Dysfunction After Drug Discontinuation. Updated 27 January 2025.
• The Australasian College of Dermatologists. Position Statement. Isotretinoin for the treatment of acne. Updated October 2024.

Disclaimer

Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, that takes into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.

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Medicines Safety Update is written by staff from our Pharmacovigilance Branch.

Editor: Dr Megan Hickie

Deputy Editor: Aaron Hall

Contributors: Rachel Holland, Tuong-Vi Phan and Albert Cui