Overview:

Oral retinoids are vitamin A derivatives which are used to treat severe acne, severe forms of psoriasis, and other skin conditions¹. There are three (3) types of oral retinoids registered in Malaysia, namely isotretinoin, tretinoin and acitretin.

Background:

NPRA has received information from the European Medicines Agency (EMA) regarding the possible risk of neuropsychiatric symptoms such as depression, anxiety and suicidal behavior associated with the use of oral retinoids.

Severe skin disorders are known to have a correlation to the increase in risk of psychiatric disorders². EMA has recently completed a safety review based on the link of oral retinoids use with neuropsychiatric disorders. The review was conducted by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) which evaluated data from published literature, post-marketing reports, written submissions and additional information received from stakeholder meetings. It was found that the available data had several important limitations that prevented the establishment of a clear causal association – whether the risk of neuropsychiatric symptoms was due to the use of retinoids. However, patients with severe skin conditions may be more susceptible to develop neuropsychiatric symptoms due to the nature of the disease.

Considering the target patient population and possible underlying risk of psychiatric disorders, and that the existing product information on the risk of neuropsychiatric disorders is inconsistent across the entire class of oral retinoids, EMA has affirmed that an update to the prescribing information for this class should include a warning about this risk. Topical retinoids do not carry a risk of neuropsychiatric side effects, therefore no additional warning to the prescribing information is required.

Adverse Drug Reaction Reports:

NPRA has received 74 ADR reports related to oral retinoids. To date, there is no report of neuropsychiatric symptoms associated with the use of oral retinoids received³.

Advice for Healthcare Professionals:

• Rare cases of depression, depression-aggravated anxiety and mood alterations have been reported in patients taking oral retinoids.
• Patients taking oral retinoids and their caretakers should be advised to be alert on changes in mood and/or behaviour and to seek medical advice if this occurs.
• Special precautions should be taken in prescribing oral retinoids in patients with history of depression.
• Monitor for signs and symptoms of depression and refer patients for appropriate treatment if necessary.
• Topically applied retinoids have negligible systemic absorption, therefore are unlikely to cause psychiatric disorders.
• Healthcare professionals are encouraged to report all adverse drug reactions associated with retinoids to NPRA.

A directive [Ruj. Kami: (6) dlm. BPFK/PPP/07/25 Jld. 3] has been issued by NPRA for updates to the local product packaging insert and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) related to this safety issue. Please refer to the directive for more information.

References:

1. European Medicines Agency (2018). Updated measures for pregnancy prevention during retinoid use. EMA/165360/2018.
2. European Medicines Agency (2018). Assessment report: Referral under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data: Retinoids containing medicinal products. EMA/254364/2018.
3. The Malaysian Adverse Drug Reactions database, NPRA [Accessed: January 2019].

DISCLAIMER
This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.