Join the Fight for Montelukast Safety

Montelukast (brand name Singulair) is a prescription medication approved by the FDA for asthma and allergies

(1) to prevent asthma attacks and for long-term treatment of asthma in adults and children 1 year and older

(2) to prevent exercise-induced asthma in patients 6 years and older

(3) to help control the nasal symptoms of seasonal outdoor allergies in patients 2 years and older and year-round indoor allergies in those 6 months and older.

Montelukast helps improve symptoms of asthma and allergic rhinitis by blocking substances in the body called leukotrienes.

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

Montelukast is not effective for everyone. Research indicates that response is partly due to genetic differences.

Prescribing Information and Medication Guide for Montelukast (Singulair)

An FDA approved Medication Guide is 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

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

“The U.S. Food and Drug Administration (FDA) is strengthening existing warnings about serious behavior and mood-related changes with montelukast (Singulair and generics), which is a prescription medicine for asthma and allergy.

We are taking this action after a review of available information led us to reevaluate the benefits and risks of montelukast use. Montelukast prescribing information already includes warnings about mental health side effects, including suicidal thoughts or actions; however, many health care professionals and patients/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, and therefore determined that a Boxed Warning was appropriate.

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.”

Montelukast may cause various neuropsychiatric side effects, including:

agitation
aggressive behavior or hostility
anxiousness
depression
disorientation
disturbance in attention
dream abnormalities
dysphemia (stuttering)
hallucinations (seeing/hearing/feeling things that aren’t there)
insomnia
irritability
memory impairment
obsessive-compulsive symptoms
restlessness
somnambulism (sleep walking)
suicidal thinking and behavior (including suicide)
tic (repetitive movement or sound that is difficult to control)

tremor

It is essential that patients/caregivers monitor for mood and behavioral changes while taking montelukast and contact their healthcare provider immediately if these happen.

Other side effects may include:

increased bleeding tendency, thrombocytopenia

hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration

drowsiness, paraesthesia/hypoesthesia, seizures

palpitations

epistaxis (nosebleed), pulmonary eosinophilia

diarrhea, dyspepsia, nausea, pancreatitis, vomiting

cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury

angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticaria

arthralgia, myalgia including muscle cramps

enuresis in children

edema

Patients with asthma on therapy with montelukast may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These reactions have been sometimes associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.

Prescribing Information for montelukast (Singulair)

Parents have reported to us that:

(1) side effects began days, weeks, months or more after treatment began.

(2) side effects began or worsened after a dosage increase.

(3) side effects began after stopping and re-starting montelukast.

(4) side effects began after changing from brand name to generic or from one brand of generic to another.

(5) side effects took days, weeks, months or more to resolve after stopping montelukast.
(6) side effects worsened/began after stopping montelukast.

FDA recognizes that side effects may occur during or after montelukast use: “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.”

Continuing 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.“

Withdrawal from Montelukast is documented in the medical literature. Neuropsychiatric Event on Withdrawal of Montelukast

According to FDA, the risk of side effects is unknown. Only an estimated 10% of side effects from medications are reported to FDA, and healthcare professionals are not required to report them.

A 2019 study found that “Children with asthma who experienced a new-onset neuropsychiatric event had nearly twice the odds of having been prescribed montelukast in the year before their event.”

A 2022 study suggests that adverse drug reactions are more likely to occur in children, due to the early maturation stage of their brains.

Montelukast crosses the blood-brain barrier and interferes with brain receptors it was not intended to target.

According to FDA: “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.”

NIH Guidelines for the Diagnosis and Management of Asthma

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

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.