Montelukast, an oral leukotriene receptor antagonist marketed under the brand name Singulair® (Organon Pharma), was the subject of a pharmacovigilance alert in 2019, in which the MHRA warned prescribers to be alert to neuropsychiatric reactions and to “ carefully consider the benefits and risks of continuing treatment if they occur. » This alert follows a review by the European Medicines Agency (European Medicines Agency) who identified “ cases where neuropsychiatric reactions were recognized late as a possible adverse drug reaction ».
In 2020, the ANSM also reminded healthcare professionals of this risk.
A 2022 review conducted by the University of Oxford found an 11% increase in the risk of incident neuropsychiatric diagnoses while taking montelukast. It was noted that, in some cases, adverse symptoms disappeared after stopping treatment, but recurred after restarting the drug.
Families say they were not warned of the risks
This latest decision follows pressure from families who claim they were not properly warned of the risks associated with this drug, with children as young as three years old having suffered “ traumatic side effects » such as night terrors, depression and, in rare cases, hallucinations or suicidal behavior.
In the United States, the Food and Drug Administration (Food and Drug Administration) has insisted since 2020 that the drug carry a black boxed safety warning about serious mental health side effects, including suicidal thoughts and actions.
A UK Montelukast Action Group, which claims to represent almost 3,500 families, has also campaigned for more visible warnings in the UK, as well as tighter controls and support for those affected. The group includes a couple, whose son committed suicide at the age of 14 while taking the drug, and who want the investigation reopened. Other parents reported that people affected by the drug walked in front of vehicles, jumped out of cars and windows in extreme distress, and used knives to harm themselves or threaten others.
Thousands of reports of adverse reactions
Alison Cave, chief safety officer at the MHRA, told the magazine BMJ : « We listened to patients’ experiences and learned from them. This information forms an important part of our evaluations and decision-making. » She encouraged patients and caregivers to report any adverse reactions via the yellow card program (Yellow Card), which received a record 143 reports of psychiatric conditions associated with the drug in 2023. Since the drug’s launch in 1998, the program has received a total of 3,274 spontaneous reports of adverse reactions, including 1,876 classified as serious, with 25 deaths.
Anna Murphy, Consultant Respiratory Pharmacist at University Hospitals of the National Health Service Leicester (University Hospitals of Leicester NHS Trust), declared this week to the magazine Pharmaceutical Journal that some asthma phenotypes appeared to be particularly sensitive to montelukast. She advised prescribers to initiate the drug as a 4- to 6-week trial and to continue it only if the benefit is judged to outweigh the risk.
The 2019 alert also advised doctors to be alert to the newly recognized neuropsychiatric reactions of slurred speech (stuttering) and obsessive-compulsive symptoms. A freedom of information request to the MHRA in 2022 found that montelukast was then the second most commonly reported drug cause of obsessive-compulsive disorder.
Other known neuropsychiatric reactions to montelukast include sleep disturbances, depression and agitation which may affect up to 1 in 100 users, nightmares, aggression and behavioral changes, particularly in children; and attention or memory problems.
The MHRA review is currently being finalized.
This article was translated from Medscape.co.uk using multiple editorial tools, including AI, in the process. The content was reviewed by the editorial staff before publication.
