Therapeutic Goods Administration Australia (2025)
Montelukast safety alert, Highlighted safety warnings about possible side effects, 16 January
https://www.tga.gov.au/news/safety-alerts/montelukast-safety-alert
Montelukast is a prescription medicine used to prevent and treat chronic asthma in adults and children aged 2 years and older. It is also used to treat the symptoms of seasonal allergic rhinitis (hay fever).
Extra safety information is being added to all montelukast products to highlight the existing warnings about serious behaviour and mood-related changes that have been reported in patients taking this medicine. The safety information includes:
- a new warning at the start of the Product Information and Consumer Medicine Information sheets
- additional information for doctors and patients on what to do if serious behaviour and mood-related changes happen.
Please note that this is not new information. It is a reminder to watch out for these possible side effects if taking montelukast.
What patients or their carers should do
You should immediately let your doctor know if you, your child or someone you care for who is taking montelukast starts to have:
- agitation, including aggressive behaviour and/or hostility (such as temper tantrums in children)
- suicidal thoughts and actions
- tremor (trembling or shaking)
- irritability, restlessness
- anxiousness, depression (sad mood)
- disorientation (can’t tell the correct time, where you/they are or who someone you/they know is)
- difficulty concentrating or remembering things
- hallucinations (seeing, feeling or hearing things that are not there)
- difficulty sleeping, episodes of sleep-walking.
What health professionals should do
Be alert to the updated warnings in the montelukast Product Information- external site.
Health professionals should:
- look out for neuropsychiatric reactions in patients taking montelukast and discontinue treatment if new or worsening symptoms occur
- advise patients and their carers to be alert for changes in behaviour or for new neuropsychiatric symptoms and to seek medical advice immediately if they occur
- provide the Consumer Medicine Information- external site to patients to remind them of these effects, if needed.
For more detailed information written for health professionals, including the full text of the additional warnings, see the Medicine Safety Update article.
Therapeutic Goods Administration Australia (2025)
More prominent safety warnings about the neuropsychiatric effects of montelukast, 16 January
Summary
Montelukast is a prescription medicine used to prevent and treat chronic asthma in adults and children aged 2 years and older, and for symptomatic seasonal allergic rhinitis (hay fever).
Additional safety information is being added to all montelukast products to strengthen and highlight existing warnings about serious neuropsychiatric events. These include behavioural changes, depression and suicidal thoughts and behaviour. The safety information includes:
- a new boxed warning
- additional guidance for prescribers and patients on the management of serious neuropsychiatric events.
This safety update follows a TGA safety investigation conducted in 2024 after international regulators strengthened warnings about neuropsychiatric events for montelukast products.
The update brings the Australian Product Information- external site (PI) and Consumer Medicine Information- external site (CMI) in line with international regulatory advice.
What health professionals should do
Health professionals are reminded about the potential neuropsychiatric effects associated with montelukast. These effects have been reported in all age groups taking montelukast, are generally mild and may occur by chance. However, symptoms can be serious and continue if treatment is not stopped. In rare cases, patients taking montelukast have died after experiencing suicidal behaviour.
Health professionals should be vigilant for neuropsychiatric reactions in patients taking montelukast and discontinue treatment if new or worsening symptoms occur.
Advise patients and their carers to be alert for changes in behaviour or for new neuropsychiatric symptoms and to seek medical advice immediately should they occur. Consider providing the CMI to remind patients of these effects.
Background
The risks of neuropsychiatric events with montelukast are already well documented in both the PI and CMI.
In July 2018, the TGA published a review of montelukast and neuropsychiatric adverse events. This evaluated the medical literature and included consultation with international regulators and expert advice from the Advisory Committee on Medicines (ACM).
In 2024, an updated TGA safety investigation was conducted after international regulators strengthened their warnings about neuropsychiatric events. Expert advice from the ACM concluded that up-to-date information did not identify any new neuropsychiatric risks and existing evidence for the association between montelukast and neuropsychiatric risks remained uncertain.
The expert group recommended adding a boxed warning in the Australian PI to align with international regulators.
Adverse events reported to us
A search of our publicly available Database of Adverse Event Notifications (DAEN) on 18 December 2024 identified 356 cases for montelukast and psychiatric disorders.
The most commonly reported symptoms were aggression (100 cases), anxiety (87 cases), suicidal ideation (72 cases), depression (71 cases), insomnia (52 cases) and nightmare (50 cases).
There were 91 reports that mentioned suicidal behaviours. Of these, 10 reported a fatal outcome.
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
The following boxed warning will be included in the Australian PIs for montelukast products.
WARNING:
Serious neuropsychiatric events
Neuropsychiatric events such as behavioural changes, depression and suicidality have been reported in all age groups taking montelukast (see sections 4.4 and 4.8). Events are generally mild and may be coincidental. However, the symptoms may be serious and continue if the treatment is not withdrawn. Therefore, the treatment with montelukast should be discontinued if neuropsychiatric symptoms occur during treatment. Advise patients and/or caregivers to be alert for neuropsychiatric events and instruct them to notify their physician if these changes in behaviour occur.
Additional advice to prescribers will also be included in the existing information on neuropsychiatric events in Section 4.4 Special warnings and precautions of the PI, as follows:
Neuropsychiatric events
Prescribers should discuss the benefits and risks of montelukast use with patients and caregivers when prescribing montelukast. Patients and/or caregivers should be advised to be alert for changes in behaviour or for new neuropsychiatric symptoms when taking montelukast. If changes in behaviour are observed, or if new neuropsychiatric symptoms or suicidal thoughts and/or behaviour occur, patients should be advised to discontinue montelukast and contact a healthcare provider immediately. In many cases, symptoms resolved after stopping montelukast therapy; however, in some cases symptoms persisted after discontinuation of montelukast. Therefore, patients should be monitored and provided supportive care until symptoms resolve. Prescribers should carefully evaluate the risks and benefits of continuing treatment with montelukast if such events occur.
Further reading
TGA Montelukast Safety Review, July 2018: Montelukast safety review
ACM April 2018 meeting: ACM meeting statement, Meeting 8, 5-6 April 2018
ACM August 2024 meeting: ACM meeting statement, Meeting 46, 1 and 2 August 2024
What to report? You don’t need to be certain, just suspicious!
We encourage the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, and herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines (look for the Black Triangle ▼ in PI and CMI documents – this symbol identifies medicines that are new or being used differently)
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
To report a suspected side effect or for more information about reporting, go to our ‘Report problem or side effect’ webpage or contact our Pharmacovigilance Branch ADR.Reports@health.gov.au.
Therapeutic Goods Administration Australia (2024)
Mountelukast and Neuropsychiatric Events
Montelukast is a medicine prescribed for asthma or allergic rhinitis.
The origin of this signal investigation was notification by the TGA’s international regulatory counterparts that their existing warnings about neuropsychiatric effects in montelukast product information documents will be strengthened. In addition, the TGA has been approached by consumer advocacy groups who have informed the TGA that in their view patients and prescribers are not adequately aware of the risks.
Montelukast and associated neuropsychiatric events were considered by the ACM in their 8th meeting, in April 2018. A safety alert on this issue was published by the TGA in July 2018.
At the 46th meeting, the ACM advised that the term ‘neuropsychiatric events’ encompasses too wide a range of symptoms and presentations to be meaningful and confuses symptoms with diagnosis. However, the ACM acknowledged that this term is used by international regulators. The ACM was asked to provide advice on the TGA’s current risk mitigation strategies for Montelukast and how these related to that of international regulatory counterparts. Specifically, the ACM was asked to advise whether a boxed warning should be added to the Australian PI regarding the association with neuropsychiatric adverse events.
The ACM advised that a 2024 review of the evidence did not identify any new neuropsychiatric risks associated with montelukast. The existing evidence for the potential association between montelukast and neuropsychiatric risks is uncertain, and has not changed.
However, on balance, the ACM advised that while the scientific and clinical evidence to 2024 does not demonstrate a causal association between montelukast and neuropsychiatric symptoms, alignment with international regulators in this case and in acknowledgment of consumer concerns, it would now be appropriate to implement a boxed warning.
In formulating the boxed warning, the ACM supported careful wording that neuropsychiatric events (with examples) are generally mild and may be coincidental.
The ACM also recommended additional changes to the Australian PI to add wording around discontinuation of montelukast if neuropsychiatric symptoms emerge, in line with wording found in the Canadian monograph.
UK Medicines and Healthcare Products Regulatory Agency (2024)
Montelukast: reminder of the risk of neuropsychiatric reactions
https://www.gov.uk/drug-safety-update/montelukast-reminder-of-the-risk-of-neuropsychiatric-reactions
Healthcare professionals prescribing montelukast should be alert to the risk of neuropsychiatric reactions in all patients including children and adolescents. Reported neuropsychiatric reactions include sleep disorders, hallucinations, anxiety and depression, as well as changes in behaviour and mood. Healthcare professionals should advise patients and their caregivers to be alert to these risks and seek medical advice as soon as possible if neuropsychiatric reactions occur.
Taiwan Food and Drug Administration (2021)
FDA limits drugs containing montelukast
Taipei Times, 8 December 2021
https://www.taipeitimes.com/News/taiwan/archives/2021/12/08/2003769221
“The Food and Drug Administration (FDA) has imposed restrictions on the prescription of drugs containing montelukast for people with allergic rhinitis, ruling that such medications should only be prescribed after other drugs have been used and failed to be effective. Drugs containing montelukast could affect a person’s mental health while they are taking the medication or after treatment has stopped, with side effects including changes in behavior, unusual movements or suicidal thoughts, the FDA said in a statement yesterday.
Hung Kuo-teng (洪國登), head of the FDA’s Medicinal Products Division, told reporters that there are 31 drug permit licenses that have been issued in Taiwan for medications containing montelukast, which is used to treat asthma and allergic rhinitis, a type of nasal inflammation that occurs when the immune system overreacts to allergens in the air. Citing National Health Insurance data, Hung said that each year, about 900,000 prescriptions of medication containing montelukast are given out.
Last year, the US Food and Drug Administration issued a warning against drugs containing montelukast, saying that their clinical effectiveness was not shown to be greater than the potential risk they posed to people’s mental health. It then determined that they should not be used until other medications for allergic rhinitis have been used and found to be ineffective, Hung said.
In light of the warning, Taiwan’s FDA re-evaluated the effectiveness and risk of such medications, and its drug safety assessment panel determined that while drugs containing montelukast are effective in treating allergic rhinitis, they might also cause people to develop mental health problems, Hung said. As a result, the agency has decided to list those medications as “rear-line” drugs, meaning that they can only be prescribed when other medications for nasal inflammation caused by allergies have failed to be effective, Hung said, adding that there are other drugs for treating asthma.
The ruling went into effect immediately. The companies that hold permit licenses for drugs containing montelukast have been told to change the content of their package inserts before July 31 so that they state that the drugs can only be used when other medications for allergic rhinitis have failed to be effective, Hung said. Companies that fail to make the change before the deadline would have their drug permit license revoked, Hung said.”
Sri Lankan National Medicines Regulatory Authority (2021)
8 October 2021
NMRA requires box warning and information for patient/care giver about serious mental health and side effects for asthma and allergy drug Montelukast to be included in the package insert (PIL) of the each and every commercial pack of Montelukast products -all oral dosage forms. And, Amended package insert/product information leaflet (PIL) need to be submitted to the NMRA within three months of this notice.
| RISK OF NEUROPSYCHIATRIC REACTIONS: Healthcare professionals are advised to be alert for neuropsychiatric reactions, including changes in behavior, speech impairment, depression and obsessive-compulsive symptoms, in adults, adolescents, and children taking montelukast. The risks and benefits of continuing treatment should be evaluated if these reactions occur. Patients should be advised to read the list of neuropsychiatric reactions in the product information leaflet and seek immediate medical attention if they occur. |
US Food and Drug Adminstration (2020)
The FDA requires Boxed Warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis
“On March 4, 2020 FDA strengthened existing warnings about serious behavior and mood-related changes with montelukast (brand name Singulair), a prescription medicine for asthma and allergy. We are taking this action after a review of available information that led us to reevaluate the benefits and risks of montelukast use. Prescribing information already includes warnings about mental health side effects, including suicidal thoughts or actions; however, many health care professionals, patients and caregivers are not aware of the risk.
We decided a stronger warning is needed after conducting an extensive review of available information and convening a panel of outside experts. We are requiring a Boxed Warning, our most prominent warning, be added to the prescribing information to describe these serious mental health side effects. We are also requiring a new patient Medication Guide to educate patients about the medicine. We reviewed case reports submitted to FDA, conducted an observational study using data from the FDA’s Sentinel System, and reviewed observational and animal studies in the published literature. Given the available information, we also reevaluated the benefits and risks of use of montelukast and determined it should not be the first-choice treatment for mild allergic rhinitis.
Health care professionals should consider the risks and benefits of montelukast when deciding to prescribe or continue patients on the medicine. Counsel all patients about mental health side effects and advise them to stop the medicine and contact a health care professional immediately if they develop any symptoms. Only prescribe montelukast for allergic rhinitis in patients who have an inadequate response or intolerance to alternative therapies and for patients with asthma, we recommend that health care professionals consider the benefits, and risks of mental health side effects, before prescribing montelukast.
We continue to receive reports of mental health side effects with montelukast use. A wide variety of mental health side effects have been reported, including completed suicides. Some occurred during montelukast treatment and resolved after stopping the medicine. Other reports indicated that mental health side effects developed or continued after stopping montelukast.”
Health Canada (2020)
Key messages for healthcare professionals:
- Serious neuropsychiatric (NP) events have been reported in patients with and without a previous history of psychiatric disorder during Singulair treatment and after its discontinuation. The mechanisms underlying NP events associated with Singulair use are currently not well understood.
- Highly variable NP event types were reported with the use of Singulair including, but not limited to, agitation, aggression, depression, sleep disturbances, suicidal thoughts and behaviour (including suicide).
- The benefits of Singulair may not outweigh the risks in some patients due to the risk of serious NP events, particularly when the symptoms of the disease may be mild and adequately treated with alternative therapies.
- The use of Singular should be reserved for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies. In patients with asthma or exercise-induced bronchoconstriction, healthcare professionals should consider the benefits and risks before prescribing Singulair.
- Although in many cases NP symptoms resolved after stopping Singulair therapy, in some cases symptoms persisted after discontinuation of Singulair. Patients should be monitored and provided supportive care until NP symptoms resolve.
- Healthcare professionals are reminded to advise patients and/or caregivers to:
- be alert for changes in behaviour or new NP symptoms when taking Singulair;
- discontinue Singulair and contact a healthcare professional immediately if changes in behaviour are observed, or if new NP symptoms or suicidal thoughts and/or behaviour occur.
Health Sciences Authority Singapore (2020)
In March 2020, HSA initiated a safety review on montelukast in response to the regulatory actions taken by the US Food and Drug Administration (FDA)1 to include a Boxed Warning on serious behaviour and mood-related changes with montelukast and to restrict the use of montelukast in the treatment of allergic rhinitis in patients with inadequate response or intolerance to alternative therapies. FDA’s review did not identify new evidence regarding the known neuropsychiatric safety concern but highlighted a lack of awareness of healthcare professionals to this safety issue despite earlier communications by the agency.
Internationally, several regulatory agencies had also incorporated restrictions to the use of montelukast in allergic rhinitis. In July 2020, Health Canada adopted similar measures as the US FDA.2 In the United Kingdom, montelukast is only indicated for symptomatic relief of seasonal allergic rhinitis in patients with asthma.
HSA has received a small number of reports of neuropsychiatric events associated with the use of montelukast since its registration in Singapore in 1998. The events include aggressive behaviour, agitation, depression, tremor, hallucinations, hyperactivity, and sleep disturbances such as somnolence, insomnia and nightmares.
Healthcare professionals are advised of the following, when considering the use of montelukast:
- To consider the benefits of treatment with montelukast and its risks of neuropsychiatric effects before prescribing montelukast
- To discuss with their patients and/or caregivers on the benefits and risks of treatment when prescribing montelukast. Healthcare professionals may make use of the patient educational material available for montelukast (e.g. article on MOH Health Hub6) for patient counselling
- To advise their patients and/or caregivers to be alert to changes in behaviour or new neuropsychiatric symptoms when taking montelukast and to seek medical attention if neuropsychiatric symptoms occur
HSA has issued a Dear Healthcare Professional Letter on 30 October 2020 to inform healthcare professionals of the advisory on the new restriction on montelukast use and neuropsychiatric events.7 HSA is working with the product registrants of montelukast-containing products to update the local PIs with the new recommendations on the indicated use of montelukast in allergic rhinitis and additional safety information on the risk of neuropsychiatric AEs.
Healthcare professionals are encouraged to report any suspected serious AEs related to montelukast to the Vigilance and Compliance Branch of HSA.
Drug Regulatory Authority of Pakistan (2020)
Advice for Healthcare Professionals:
Health care professionals should consider the risks and benefits of montelukast when deciding to prescribe or continue patients on the medicine.
Only prescribe montelukast for allergic rhinitis in patients who have an inadequate response or intolerance to alternative therapies.
Consider the risks and benefits of montelukast when deciding to prescribe or continue patients on the medicine.
Advise all patients of the risk of neuropsychiatric events when prescribing montelukast.
Advise patients and parents/caregivers that the patient should stop taking montelukast and contact a health care professional immediately if changes in behavior or new neuropsychiatric symptoms, suicidal thoughts or behavior occur.
Monitor all patients treated with montelukast for neuropsychiatric symptoms. Events have occurred in patients with and without pre-existing psychiatric disease.
Report neuropsychiatric or any other suspected adverse drug reaction to Pakistan National Pharmacovigilance Centre, DRAP.
Advice for Patients/Caregivers and Relatives:
Serious mental health side effects have occurred in patients with and without a history of mental illness.
Stop taking montelukast and notify a health care professional right away if you or your child experience behavior or mood-related changes while taking the medicine. These may include: agitation, including aggressive behavior or hostility, attention problems, bad or vivid dreams, depression, disorientation or confusion, feeling anxious, hallucinations (seeing or hearing things that are not really there), irritability, memory problem, obsessive-compulsive symptom, restlessness, sleepwalking, stuttering, suicidal thoughts and actions, tremor or shakiness, trouble sleeping, uncontrolled muscle movements.
Talk to your health care professional about any history of mental illness before starting treatment.
You should take montelukast for allergic rhinitis or hay fever only if you cannot tolerate other medicines or they do not work for you. Many other safe and effective allergy medicines are widely available, talk to your healthcare professionals in case you intend to change montelukast for allergic rhinitis.
Italian Medicines Agency (2020)
ANSM France (2020)
Saudi Food and Drug Authority (2019)
https://www.sfda.gov.sa/sites/default/files/2020-11/MontelukastSafetyCommunication.pdf
SAFETY COMMUNICATION, 10 October 2019
Montelukast: reminder of the risk of neuropsychiatric reactions
The Saudi Food and Drug Authority (SFDA) would like to inform healthcare professionals about the occurrence of neuropsychiatric reactions in patients using montelukast.
> Be alert for neuropsychiatric reactions in patients using montelukast; events have been reported in adults, adolescents, and children
> Advise patients and their caregivers to read carefully the list of neuropsychiatric reactions in the patient information leaflet and seek medical advice immediately should they occur
> Evaluate carefully the risks and benefits of continuing treatment if neuropsychiatric reactions occur
> Be aware of newly recognised neuropsychiatric reactions of speech impairment (stuttering) and obsessive–compulsive symptoms
Neuropsychiatric reactions may occur in association with montelukast treatment, and these reactions are listed as possible side effects in the product information. A recent review confirmed the known risks of neuropsychiatric reactions and found that the magnitude of risk was unchanged. However, the review identified some cases in which there had been a delay in neuropsychiatric reactions being recognised as a possible adverse drug reaction. Therefore, we remind healthcare professionals about the possible risks with montelukast and the need to consider the benefits and risks of continuing treatment if they occur.
Health Products Regualtory Authority Ireland (2019)
Montelukast – Reminder of risk of neuropsychiatric reactions and product information update, August 2019
Therapeutic Goods Administration Australia (2018)
Montelukast Safety review, 12 July 2018
https://www.tga.gov.au/alert/montelukast
“The TGA is undertaking additional risk mitigation activities following a new safety review of montelukast. The review evaluated literature published since 2013 (when the issue was last reviewed) and included consultation with international regulators and obtaining expert advice from the Advisory Committee on Medicines (ACM). This approach has the support of the Royal Australian College of General Practitioners (RACGP) and the Australian Medical Association….
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 Product Information (PI) for montelukast contains a precaution about this risk. The Government requested the latest safety review following reports in the media of serious neuropsychiatric events occurring in association with montelukast in children and adolescents.
Expert advice and TGA actions
The ACM reviewed the issue on 5 April 2018 and offered the following advice (see meeting statement):
- In current clinical practice, montelukast is a useful first-line treatment for mild to moderate asthma in a small but well-defined population.
- It would be helpful if the TGA liaised with various authoring bodies of guidance documents used by prescribers and asthma nurse educators to insert advice similar to that in the Asthma Australia fact sheet, which provides one page of consumer-friendly advice on this issue. They also recommended
- liaison with relevant parties who provide templates for asthma management plans to include a prompt in these plans regarding counselling on potential neuropsychiatric events
- inclusion of the Consumer Medicine lnformation (CMI) in the packaging and encouraged active provision of the CMl to the parent/carer, with counselling, at the point of dispensing.
- Liaison with the Australian Paediatric Surveillance Unit may be useful to provide additional Australian data on the association between montelukast and neuropsychiatric events.
- Consideration could be given to developing a more general consumer educational activity using montelukast as an example.
In response to the ACM’s advice and the findings of its safety review, the TGA has:
- written to State and Territory health departments, NPS MedicineWise, Health Direct and Therapeutic Guidelines to formally request inclusion of advice regarding montelukast and neuropsychiatric events in relevant clinical guidelines and educational activities.
- written to all sponsors of montelukast to request inclusion of the CMI in the packaging with information regarding potential neuropsychiatric events
- contacted the Australian Paediatric Surveillance Unit about potentially including montelukast and neuropsychiatric events in their monthly survey of clinicians.
Information for consumers
If you or someone you provide care for takes montelukast, please be aware of the potential for neuropsychiatric events (such as agitation, sleep disturbance and depression) associated with this medicine. If you notice a change in behaviour, seek medical attention. If the patient is a child or adolescent, or the symptoms are severe (such as suicidal thinking or behaviour), seek urgent medical attention. If you have any questions or concerns about this issue, talk to your health professional.
Information for health professionals
You are reminded of the known association between montelukast and neuropsychiatric events, particularly when initiating therapy or increasing the dose. This is especially important if your patient is a child. Prescribers should consult the PI for further information on potential neuropsychiatric adverse events and carefully evaluate the risks and benefits of continuing treatment with montelukast if such events occur. When treating children with montelukast, the TGA recommends that you also educate caregivers about these potential adverse effects and consider providing them the CMI. Advise them to seek medical advice if they have any concerns.”