Medicines Healthcare Products Regulatory Agency
Advice for healthcare professionals:
- the warnings in the Patient Information Leaflet and Summary of Product Characteristics for all montelukast products in the UK have been strengthened and highlighted with a black box for greater emphasis
- be alert for neuropsychiatric reactions in patients taking montelukast; events have been reported in adults, adolescents, and children
- discontinue montelukast if patients experience new or worsening symptoms of neuropsychiatric reactions
- advise patients and their caregivers to carefully read the list of neuropsychiatric reactions in the Patient Information Leaflet and to seek medical advice immediately should they occur
- report all suspected adverse drug reactions associated with montelukast to the Yellow Card scheme
Advice for healthcare professionals to give to patients and caregivers:
- infrequently, some patients may experience new or worsening changes in mood, sleep or behaviour such as nightmares, aggression, anxiety or thoughts about self-injury while using montelukast
- you should seek immediate medical attention if you or your child experiences these symptoms; your prescriber is best placed to advise you on stopping this medicine if needed
- it is very important to tell your friends and family that you are taking montelukast and that this medicine is associated with infrequent neuropsychiatric side effects. This is because you may not notice some changes in your mood, sleep and behaviour. Other people may notice changes or new symptoms that you need to talk to your prescriber about
- the Patient Information Leaflet that comes with all montelukast products now includes warnings and advice about these psychiatric side effects in a black box
- it is important to read the Patient Information Leaflet that comes with your medicine or your childs medicine
- talk to a healthcare professional if you or your child are experiencing any problems with the medicine
- patients, parents, and caregivers can report suspected adverse drug reactions to montelukast via the Yellow Card scheme
Review of neuropsychiatric reactions with montelukast
To increase awareness of the risks of neuropsychiatric effects with montelukast, new boxed warnings will be introduced to the Summary of Product Characteristics (SmPC) and Patient Information Leaflet (PIL) to make these risks more prominent to the reader. These warnings have been updated with the current evidence on the risk. Healthcare professionals and patients should familiarise themselves with this information.
It is well established that neuropsychiatric reactions may infrequently occur in association with montelukast. These are documented in the SmPC and PIL of all marketed montelukast products in the UK. A Drug Safety Update was published in September 2019 to remind healthcare professionals and patients of the risk of neuropsychiatric reactions with montelukast.
Since these actions were implemented, the MHRA has continued to receive Yellow Card reports and queries from patients and caregivers. The MHRA has therefore conducted a further review to evaluate the new evidence, taking into consideration the experiences of patients and caregivers and independent clinical advice from paediatricians, specialists in mental health and respiratory health, as well as experts in medicines safety at Expert Advisory Groups of the Commission on Human Medicines.
Review of the Yellow Card data has indicated a potential lack of awareness of the risk of neuropsychiatric reactions with montelukast amongst healthcare professionals, patients and their caregivers. Based on the overall evidence, the Pharmacovigilance Expert Advisory Group (PEAG) advised that montelukast should be immediately withdrawn due to the nature of the neuropsychiatric reactions, and that immediate withdrawal may help prevent escalation to more serious events. Therefore, updates to the product information have been implemented to ensure patients and healthcare professionals are aware of these risks and what action should be taken.
UK reports of neuropsychiatric reactions with montelukast
A range of neuropsychiatric reactions have been reported in association with montelukast. Among these are:
- sleep disturbances, depression and agitation including aggressive behaviour (may affect up to 1 in 100 people taking montelukast)
- disturbances of attention or memory (up to 1 in 1,000 people)
- very rarely, hallucinations and suicidal thinking and behaviour (up to 1 in 10,000 people).
See the SmPC (section 4.8) and the PIL (section 4) for full details.
Since first authorised in the UK in 1998, there have been approximately 44 million prescriptions of montelukast issued. During this time, the MHRA has received 1,223 reports of suspected neuropsychiatric adverse reactions. Information on neuropsychiatric reactions with montelukast was first introduced in the SmPC in 2008 and a detailed warning was added in 2019.
Of these, the most frequently reported suspected neuropsychiatric reactions associated with montelukast for all age groups were sleep disorders, hallucinations, anxiety and depression, as well as changes in behaviour and mood. The most frequently reported reactions in younger children (up to and including 12 years old) were aggression, nightmares and anxiety while in older children (13 years old up to and including 17 years old) the most commonly reported were anxiety, suicidal ideation and depression.
About montelukast
Montelukast sodium is an oral leukotriene receptor antagonist. It is indicated for patients 6 months and older:
- for the treatment of asthma as add-on therapy in those patients with mild to moderate persistent asthma who are inadequately controlled on inhaled corticosteroids and in whom as-needed short acting beta-agonists provide inadequate clinical control of asthma
- for the prophylaxis of asthma in which the predominant component is exercise-induced bronchoconstriction.
Report any suspected adverse reactions on a Yellow Card
Please continue to report suspected adverse drug reactions to the?Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
- the?Yellow Card website
- the Yellow Card app; download from the?Apple App Store?or?Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
Article citation: Drug Safety Update volume 17, issue 9: April 2024: 2