Overview

Montelukast is used to prevent and treat chronic asthma in adults and children above 12 months of age. It is also indicated in adults and children above 2 years of age for the relief of day-time and night-time symptoms of seasonal allergic rhinitis¹.

Background of Safety Issue

The National Pharmaceutical Regulatory Agency (NPRA) has received information from the United State Food and Drug Administration (US FDA) on the risk of neuropsychiatric adverse reactions (obsessive-compulsive symptoms) with the use of montelukast². It was found that there is a known association between montelukast and neuropsychiatric events (such as agitation, sleep disturbance and depression) including in rare cases, suicidal thinking and behaviour.

The package insert for montelukast has been updated with a precaution about these neuropsychiatric events but has not included obsessive-compulsive symptoms as one of the events¹. The US FDA is now evaluating the need to include obsessive-compulsive symptoms as part of the neuropsychiatric adverse reactions².

Upon review, the Australian regulatory agency Therapeutic Goods Administration (TGA) has recently published a safety review on montelukast and neuropsychiatric events³. The publication was aimed to strengthen the monitoring of montelukast and neuropsychiatric events. At present, the Australian package insert for montelukast containing products have not yet been updated with obsessive-compulsive symptoms as part of the neuropsychiatric adverse reactions.

In Malaysia, there are currently 58 registered products containing montelukast sodium. The product innovator (Singulair^®) has updated its package insert with neuropsychiatric events, but obsessive-compulsive symptoms is not listed⁴.

Adverse Drug Reaction Reports⁵

NPRA has received a total of 138 ADR reports with 233 adverse events suspected to be related to montelukast-containing products. The most reported neuropsychiatric adverse reactions are hallucination (16), followed by insomnia (8), aggression (7) and psychomotor hyperactivity (7). To date, no ADR related to obsessive-compulsive symptoms following the use of montelukast has been reported to the NPRA.

Advice for Healthcare Professionals

• Please be alert on this known association between montelukast and neuropsychiatric events, particularly during treatment initiation or dose increment, especially if the patient is a child.
• Educate the patient and his/her caregivers (if patient is a child) about the potential neuropsychiatric events and advise them to seek medical advice if there are any concerns.
• Please report all adverse events associated with the use of montelukast to the NPRA.

A directive [Ruj. Kami: (8) 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. Singulair^® Malaysian product package insert. [Last updated: August 2016]
2. United States Food and Drug Administration (August 2018). Potential signals of serious risks/new safety information identified from the FDA Adverse Event Reporting System (FAERS).
3. Therapeutic Goods Administration (July 2018). Safety review – Montelukast.
4. The NPRA QUEST 3+ database [Accessed: August 2018].
5. The Malaysian Adverse Drug Reaction database, NPRA [Accessed: August 2018].

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.