Montelukast side effects: what patients need to know

Montelukast (brand name Singulair) is a leukotriene receptor antagonist used for asthma and allergic rhinitis.

It works by blocking leukotriene D4 receptors, reducing airway inflammation and bronchoconstriction.

Common side effects in adults (affecting 1 in 10 to 1 in 100 people):

• Headache: the most frequently reported side effect, typically mild
• Abdominal pain: usually mild and transient
• Upper respiratory tract infection: reported in clinical trials, though causation is not always clear

Common side effects in children:

• Headache
• Abdominal pain
• Thirst
• Hyperkinesia: increased activity or restlessness
• Diarrhoea and nausea

Less common but recognised effects:

• Dizziness
• Drowsiness or fatigue
• Skin rash or urticaria
• Dry mouth
• Dyspepsia
• Muscle and joint pain
• Raised liver enzymes (usually transient and asymptomatic)

The overall tolerability profile of montelukast is good. In clinical trials, the incidence of side effects with montelukast was broadly similar to placebo for most reported symptoms.

The BNF notes that it is generally well tolerated when used at recommended doses.

The most important safety issue with montelukast is its potential to cause neuropsychiatric side effects. The MHRA has issued specific safety communications about this risk.

Reported neuropsychiatric effects:

• Sleep disturbances: insomnia, vivid dreams, nightmares and sleepwalking
• Agitation and restlessness
• Aggressive behaviour and irritability
• Anxiety
• Depression and low mood
• Attention and memory difficulties
• Hallucinations and disorientation (rare)
• Suicidal thoughts and behaviour (rare but serious)
• Obsessive-compulsive symptoms (rare)
• Stuttering (rare)

MHRA warnings:

In 2019 and again in 2020, the MHRA issued Drug Safety Updates emphasising that prescribers should inform patients and carers about the risk of neuropsychiatric reactions.

The warning states that these effects can occur from the first dose and may resolve after stopping the medicine.

How common are these effects?

The exact frequency is difficult to determine. Post-marketing surveillance suggests the rate may be between 1 in 100 and 1 in 1,000 patients, but under-reporting is likely.

Children and adolescents appear to be particularly susceptible.

What patients and carers should do:

• Be aware of the potential for mood and behaviour changes from the start of treatment
• Monitor children closely for sleep disturbance, nightmares, behavioural changes or aggression
• Report any new neuropsychiatric symptoms to your prescriber promptly
• Stop the medicine and seek medical advice if significant mood changes, depression or suicidal thoughts develop

Montelukast is commonly prescribed for children aged 6 months and above with asthma or allergic rhinitis. Parents and carers should be particularly vigilant about side effects.

Why children may be more affected:

• Children may be less able to describe changes in mood or perception
• Behavioural changes may be attributed to other causes (school stress, developmental phases) before the medicine is considered
• The developing brain may be more sensitive to leukotriene receptor blockade in the central nervous system

What to watch for in children:

• Nightmares or night terrors: a frequent concern reported by parents
• New-onset bedwetting in previously dry children
• Behavioural changes: increased aggression, defiance or emotional outbursts that are out of character
• Anxiety or fearfulness: new fears, separation anxiety or reluctance to go to school
• Sleep difficulties: trouble falling asleep or frequent waking
• Mood changes: unusual sadness, tearfulness or withdrawal from activities

Practical advice for parents:

• Start montelukast at a time when you can closely observe your child for 2 to 4 weeks
• Keep a brief daily diary of mood, behaviour and sleep quality
• Inform teachers and childminders that the medicine has been started, so they can report any changes they observe
• If troublesome effects develop, contact your GP. In most cases, symptoms resolve within days of stopping the medicine

NICE guidance for paediatric asthma (BTS/SIGN 2019 guideline) positions montelukast as an add-on option at steps 2 and 3 of the treatment ladder, acknowledging both its benefits and the neuropsychiatric risk.

Although uncommon, montelukast can cause allergic and dermatological reactions that patients should be aware of.

Skin reactions:

• Urticaria (hives): itchy, raised welts on the skin
• Pruritus: generalised itching without a visible rash
• Eczema exacerbation: some patients report worsening of existing eczema
• Erythema nodosum: painful red lumps, usually on the shins (rare)

Rare but serious allergic reactions:

• Angioedema: swelling of the face, lips, tongue or throat. This requires immediate medical attention
• Anaphylaxis: an extremely rare but life-threatening allergic reaction. Symptoms include difficulty breathing, widespread rash, rapid pulse and collapse. Call 999 immediately

Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis):

This is a rare vasculitis that has been reported in patients taking montelukast, particularly when oral corticosteroids are being tapered. Symptoms include:

• Worsening asthma
• Numbness or tingling in the hands and feet
• Skin rash
• Flu-like symptoms with fever
• Sinusitis

The relationship between montelukast and Churg-Strauss syndrome is debated. It may reflect unmasking of a pre-existing condition as steroids are reduced rather than a direct effect of montelukast.

The BNF advises being alert to the possibility and investigating any systemic vasculitic symptoms.

Hepatic effects:

Raised liver enzymes have been reported rarely. Very rarely, hepatitis and liver failure have occurred. Report any unexplained nausea, fatigue, dark urine or jaundice to your prescriber.

Most patients tolerate montelukast well, but for those who experience side effects, there are practical management strategies.

For headache:

• Simple analgesia such as paracetamol is usually sufficient
• Headaches often settle within the first 1 to 2 weeks of treatment
• Ensure adequate hydration

For gastrointestinal symptoms:

• Taking montelukast with food may reduce abdominal discomfort
• Symptoms are usually mild and transient

For sleep disturbance:

• Consider the timing of the dose. Montelukast is usually taken in the evening, but if nightmares or insomnia are problematic, taking it in the morning may help (though evidence is anecdotal)
• Maintain good sleep hygiene: consistent bedtime, dark room, avoiding screens
• If nightmares persist, discuss stopping the medicine with your prescriber

For neuropsychiatric effects:

• These usually resolve within days to weeks of stopping montelukast
• There is no established way to predict who will be affected
• If symptoms are mild, your prescriber may suggest monitoring for a short period to see if they settle
• If symptoms are significant (depression, suicidal thoughts, severe behavioural changes), stop the medicine and seek medical review urgently

Alternatives to montelukast:

If montelukast is not tolerated, alternatives for asthma control include:

• Inhaled corticosteroids (the cornerstone of asthma treatment)
• Long-acting beta-agonists (e.g. salmeterol, formoterol)
• Combination inhalers
• For allergic rhinitis: antihistamines and intranasal corticosteroid sprays

NICE and BTS/SIGN guidelines provide step-wise approaches to asthma management that do not depend on montelukast.

Montelukast has been available since 1998, providing over 25 years of real-world safety data.

Long-term use data:

• Clinical trials lasting up to 2 years have not identified new safety concerns with prolonged use
• The side effect profile at 12 months is broadly similar to that seen in short-term trials
• No evidence of organ toxicity with long-term use at recommended doses
• No evidence of tolerance (the medicine continues to work over time)

Periodic review:

• NICE recommends reviewing asthma treatment regularly (at least annually)
• At each review, the need for montelukast should be reassessed. If asthma is well controlled, a trial of stepping down or stopping montelukast may be appropriate
• For allergic rhinitis, seasonal use may be sufficient rather than year-round treatment

Pregnancy and breastfeeding:

• The BNF states that montelukast may be used in pregnancy if the potential benefit outweighs the risk
• Limited human data are available, but animal studies have not shown teratogenicity
• Montelukast passes into breast milk in small amounts; specialist advice should be sought

Drug interactions:

Montelukast has relatively few clinically significant drug interactions:

• CYP3A4 inducers (e.g. phenytoin, rifampicin) may reduce montelukast levels
• CYP2C8 inhibitors (e.g. gemfibrozil) may increase montelukast levels
• It is generally safe to use alongside inhaled corticosteroids, beta-agonists and antihistamines

Overall, montelukast has a well-established safety profile for long-term use, provided neuropsychiatric symptoms are monitored and acted upon promptly.