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PLEASE CONTINUE TO REPORT ALL PROBLEMS WITH MONTELUKAST TO THE US FOOD AND DRUG ADMINISTRATION'S MEDWATCH ADVERSE EVENT REPORTING PROGRAM

FILE A MEDWATCH REPORT

Adverse Event Reports are used by the FDA to identify and evaluate safety issues with medications.

If you/your child experience/s withdrawal symptoms or long term (protracted) side effects with montelukast please include this information in your report.

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DSB SCIENTISTS AND CDER’s OFFICE OF NEW DRUGS FORM MONTELUKAST WORKING GROUP

Concerns of neuropsychiatric events with montelukast were discussed at the September 2019 Pediatric Advisory Committee and Drug Safety and Risk Management Advisory Committee meeting. To address these concerns and coordinate research investigating drug-related neurological effects, a Montelukast Working Group (MWG) was formed between DSB scientists and CDER Pharmacology and Toxicology nonclinical reviewers in the Office of New Drugs.

The MWG designed studies will investigate potential mechanisms of central nervous system (CNS) effects, CNS exposure, drug accumulation potential, blood brain barrier transport, withdrawal and long-term sequelae with chronic montelukast administration. The cumulative scientific information obtained by this work will directly address the regulatory neuropsychiatric safety concerns, may impact labeling decisions for montelukast products, and will better inform healthcare providers and patients of the associated risks that should be considered for individual disease management and treatment action plans with chronic montelukast treatments.

PAGE 36 https://www.fda.gov/media/148670/download


FDA REQUIRES BOXED WARNING ABOUT SERIOUS MENTAL HEALTH SIDE EFFECTS FOR ASTHMA AND ALLERGY DRUG MONTELUKAST (SINGULAIR); ADVISES RESTRICTING USE FOR ALLERGIC RHINITIS

In March 2020, the FDA issued a Drug Safety Communication about montelukast, which included the following:

"Because of the risk of mental health side effects, the benefits of montelukast may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with other medicines.

For allergic rhinitis, also known as hay fever, we have determined that montelukast should be reserved for those who are not treated effectively with or cannot tolerate other allergy medicines.

For patients with asthma, we recommend that health care professionals consider the benefits and risks of mental health side effects before prescribing montelukast."

"Counsel all patients receiving montelukast about mental health side effects, and advise them to stop the medicine and contact a health care professional immediately if they develop any symptoms included but not limited to those listed in the table above. Be aware that some patients have reported neuropsychiatric events after discontinuation of montelukast."

"We continue to receive reports of mental health side effects reported with montelukast use. Consistent with our prior evaluations, 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."

Read the entire communication HERE


FDA PANELS ADDRESS PERSISTENT CONCERNS ABOUT MONTELUKAST SAFETY IN KIDS

September 27, 2019 - The joint meeting of the FDA's Pediatric Advisory Committee (PAC) and its Drug Safety and Risk Management Advisory Committee was held to address safety concerns voiced in a letter from Parents United for Pharmaceutical Safety and Accountability and Montelukast (Singulair) Side Effects Support and Discussion Group to the Office of Pediatric Therapeutics. In the letter, parents expressed concern about the connection between neuropsychiatric adverse events and montelukast.

https://www.medscape.com/viewarticle/919218

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WHAT IS MONTELUKAST?

Montelukast (brand name Singulair in the U.S.) is a leukotriene receptor antagonist indicated for the prophylaxis (prevention) and chronic treatment of:

- Asthma in adults and pediatric patients 12 months of age and older
- Exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older
- Seasonal allergic rhinitis in patients 2 years of age and older
- Perennial (year round) allergic rhinitis in patients 6 months of age and older


USAGE GUIDELINES FOR ALLERGIC RHINITIS WERE UPDATED IN 2020

Because the benefits of SINGULAIR may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see Warnings and Precautions (5.1)], reserve use for patients who have an inadequate response or intolerance to alternative therapies. 
1 INDICATIONS AND USAGE 1.3 Allergic Rhinitis


The 10 mg strength is NOT approved for use in children under age 15.

Montelukast is not effective for everyone. Research shows that response is partly due to genetic differences. The inter-patient variability in response is substantial (25%-60% response rate). Genetic variation in leukotriene pathway candidate genes contributes to variability in montelukast response.

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MONTELUKAST'S MENTAL HEALTH SIDE EFFECTS

Mental health (neuropsychiatric) side effects include:

agitation
aggressive behavior or hostility
anxiousness
depression
disorientation
disturbance in attention
dream abnormalities
dysphemia (stuttering)
hallucinations
insomnia
irritability
memory impairment
obsessive-compulsive symptoms
restlessnes
somnambulism (sleep walking)
suicidal thinking and behavior (including suicide)
tic (uncontrolled movements or sounds)
tremor

CLICK HERE FOR MORE INFORMATION ABOUT MONTELUKAST SIDE EFFECTS

This information is current as of March 2020.
Check dailymed for the most up to date information.
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=montelukast

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WHY DOES MONTELUKAST CAUSE MENTAL HEALTH SIDE EFFECTS?

Key findings of New Research from Portugal

Eighteen new MTK metabolites were identified. MTK's ability to react with glutathione was confirmed. The multi-omics approach employed confirmed that montelukast interferes with the glutathione detoxification system in the brain. Moreover, montelukast is also able to dysregulate various neurotransmitter and neurosteroid pathways, particularly those involved in regulation of the hypothalamic–pituitary–adrenal axis, also interfering with mitochondrial function in neuronal cells.

Results clearly indicate that montelukast therapeutic effects are accompanied by a strong modulation of specific processes in the central nervous system that may explain the observed neuropsychiatric reactions. Moreover, the results also suggest that adverse drug reactions are more likely to occur in children, due to the early maturation stage of their brains.

The mechanisms underlying montelukast's neuropsychiatric effects - new insights from a combined metabolic and multiomics approach


Montelukast crosses the blood-brain barrier.

It interferes with brain receptors it was not intended to target.

FDA proposes that "montelukast inhibition of GPR17 function on neurons and/or glial cells may contribute to the biologic processes underlying the observed neuropsychiatric events associated with montelukast treatment."

Pediatric Advisory Committee Meeting September 27, 2019 Neuropsychiatric Events with Use of Montelukast in Pediatric Patients page 14

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WHAT IS THE RISK OF SIDE EFFECTS?

According to FDA, the risk of side effects is unknown.

As of March 11, 2020, the FDA has received 14,485 reports from patients who experienced side effects. More than 10,000 of those are considered serious.

Only an estimated 10% of side effects from medications are reported to FDA, and healthcare professionals are NOT required to report them.

Children prescribed montelukast were almost twice as likely to experience a new-onset neuropsychiatric event, compared to controls on a different asthma maintenance therapy.

Montelukast and Neuropsychiatric Events in Children with Asthma: A Nested Case–Control Study

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WHEN DO SIDE EFFECTS BEGIN?

Delayed onset of side effects has been acknowledged by the FDA in an interview with Medscape, Montelukast's Underrecognized Adverse Drug Events.

"Events were noted in both adults and children, and the onset of events varied."

"In terms of timing, we have reports following initiation of montelukast and after chronic use."
 

Parents have reported to us that:

- children began experiencing side effects days, weeks, months, and even years after treatment with montelukast began.

- children experienced side effects only after a dosage increase.

- side effects intensified and/or additional side effects manifested after a dosage increase.

- side effects manifested only after stopping and re-starting the medication.

- side effects manifested after changing from brand name Singulair to generic montelukast or from one brand of generic to another.

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HOW LONG DO SIDE EFFECTS LAST?

 In many cases, symptoms resolved after stopping SINGULAIR therapy; however, in some cases symptoms persisted after discontinuation of SINGULAIR.
Singulair's Prescribing Information (5 WARNINGS AND PRECAUTIONS 5.1)


Parents have been reporting that side effects can take days, weeks, months, or years to completely resolve after stopping montelukast.

According to FDA: "Most reported cases of neuropsychiatric events occurred during montelukast treatment, but some occurred after discontinuation. In many cases, symptoms resolved after stopping montelukast; however, in some cases symptoms persisted after discontinuation from therapy or were reported after discontinuation of therapy."


PROTRACTED SIDE EFFECTS after stopping montelukast are documented on page 20 of the FDA 2000 Medical Review for Montelukast Application Number 20-830/S008.

A four year old girl developed paresthesia (sensation of ants walking on her hands and feet) two weeks into treatment with montelukast. This took 5.5 months to completely resolve after discontinuing montelukast.

PLEASE REPORT PROTRACTED (LASTING LONGER THAN EXPECTED) SIDE EFFECTS TO FDA.

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DOES MONTELUKAST CAUSE WITHDRAWAL SYMPTOMS?

Serious neuropsychiatric (NP) events have been reported with use of SINGULAIR. These postmarketing reports have been highly variable and included, but were not limited to, agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal thoughts and behavior (including suicide), tic, and tremor. NP events have been reported in adult, adolescent, and pediatric patients with and without a previous history of psychiatric disorder. NP events have been reported mostly during SINGULAIR treatment, but some were reported after SINGULAIR discontinuation. Singulair's Prescribing Information (5 WARNINGS AND PRECAUTIONS 5.1)


Neuropsychiatric Event on Withdrawal of Montelukast (March 2022)

PLEASE REPORT WITHDRAWAL FROM MONTELUKAST TO FDA.

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WHAT ARE THE ALTERNATIVES TO MONTELUKAST?

NIH updates guidelines for asthma management for first time in over a decade (December 2020)

The National Asthma Education and Prevention Program (NAEPP)
recommends that for all age groups, inhaled corticosteroids are the most effective medication for long-term control. Leukotriene receptor antagonists (including montelukast/Singulair) are considered adjunct (additional) therapy with inhaled corticosteroids, and omalizumab for severe asthma.* (Inhaled corticosteroids are not side effect free.) Reference section 3, Component 4: Medications

Diagnosis and management of rhinitis: An updated practice parameter
Intranasal corticosteroids are the preferred treatment for allergic rhinitis and when given in recommended doses are not generally associated with clinically significant systemic side effects.Page S22 [Summary Statements 74-80]

AAAAI ALLERGY AND ASTHMA DRUG GUIDE
American Academy of Allergy Asthma & Immunology

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WHERE CAN I GET SUPPORT?

Parents United for Pharmaceutical Safety and Accountability Advocates are members of the Montelukast Side Effects Support and Discussion Group, created by a Canadian mom in 2008, not long after we established PUPSA in the US. The group has since grown into an international support and advocacy group.

Join us there if you or your child experienced side effects while taking montelukast, or after stopping it, and you need support or additional information.

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WHAT ELSE SHOULD I KNOW?

The content of "consumer information leaflets" voluntarily distributed by pharmacies with prescription medications is not regulated/approved by FDA. They may not contain the most up to date information. An FDA approved MEDICATION GUIDE will be required for distribution with all prescriptions for montelukast. Read it every time you get it. If you don't get one, ask for it. The information may change if new safety issues with montelukast are identified.

A reliable source of accurate medication information is the National Library of Medicine's DailyMed website. This database includes FDA approved Prescribing Information for prescription drugs. For the most current side effect information, visit the website of the medication manufacturer and read the patient and prescribing information.

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*The EPR 3 Guidelines on Asthma were developed by an expert panel commissioned by the National Asthma Education and Prevention Program (NAEPP) Coordinating Committee (CC), coordinated by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

**Developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology, published in the Journal of Allergy and Clinical Immunology, August 2008.

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Disclaimer: Parents United for Pharmaceutical Safety and Accountability is a volunteer patient advocacy group. Consult a licensed health care professional before making any medical decisions. Do not stop administering an asthmatic child's medications without the supervision of the child's healthcare provider. The information on this site is intended for educational purposes and should not be construed as medical advice. It is accurate to the best of our knowledge. If you discover an inconsistency, please bring it to our attention.