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.
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.
FDA REQUIRES BOXED WARNING ABOUT SERIOUS MENTAL HEALTH SIDE EFFECTS FOR ASTHMA AND ALLERGY DRUG MONTELUKAST (SINGULAIR); ADVISES RESTRICTING USE FOR ALLERGIC RHINITIS
"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."
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.
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.
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.
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."
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.
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."
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.
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)
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]
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.
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.
*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.
Disclaimer: Parents United for Pharmaceutical Safety and Accountabilityis 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.
