Montelukast side effects: what patients need to know

Montelukast (brand name Singulair) is a leukotriene receptor antagonist. Doctors prescribe it for asthma and allergic rhinitis (hay fever). It blocks leukotriene D4 receptors.

This calms swelling in the airways and stops them from tightening.

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

• Headache: the most often reported side effect, and usually mild
• Abdominal pain: stomach pain that is usually mild and short-lived
• Upper respiratory tract infection: a cold or chest infection reported in trials, though the cause is not always clear

Common side effects in children:

• Headache
• Abdominal pain
• Thirst
• Hyperkinesia: being more active or restless than usual
• Diarrhoea and nausea

Less common but recognised effects:

• Dizziness
• Drowsiness or tiredness
• Skin rash or urticaria (hives)
• Dry mouth
• Dyspepsia (indigestion)
• Muscle and joint pain
• Raised liver enzymes (usually short-lived, with no symptoms)

Montelukast is well tolerated overall. In clinical trials, side effects happened about as often with montelukast as with a placebo (a dummy pill) for most symptoms.

The BNF says it is generally well tolerated at the recommended doses.

The main safety issue with montelukast is that it can affect the mind and mood. These are called neuropsychiatric side effects. The MHRA has sent out specific safety warnings about this risk.

Reported neuropsychiatric effects:

• Sleep problems: trouble sleeping, vivid dreams, nightmares and sleepwalking
• Agitation and restlessness
• Aggressive behaviour and irritability
• Anxiety
• Depression and low mood
• Trouble with attention and memory
• Hallucinations and disorientation (rare)
• Suicidal thoughts and behaviour (rare but serious)
• Obsessive-compulsive symptoms (rare)
• Stuttering (rare)

MHRA warnings:

The MHRA issued Drug Safety Updates in 2019 and again in 2020. They told prescribers to warn patients and carers about the risk of these reactions.

The warning says these effects can start from the very first dose. They may also clear up after you stop the medicine.

How common are these effects?

The exact rate is hard to pin down. Reports after the medicine went on sale suggest it may affect between 1 in 100 and 1 in 1,000 patients. The true rate is likely higher, as many cases go unreported.

Children and teenagers seem to be most at risk.

What patients and carers should do:

• Watch for changes in mood or behaviour from the start of treatment
• Watch children closely for sleep problems, nightmares, behaviour changes or aggression
• Tell your prescriber promptly about any new neuropsychiatric symptoms
• Stop the medicine and seek medical advice if you notice major mood changes, depression or suicidal thoughts

Doctors often prescribe montelukast for children aged 6 months and above. It is used for asthma or allergic rhinitis (hay fever). Parents and carers should keep a close eye out for side effects.

Why children may be more affected:

• Children may find it harder to describe changes in how they feel or what they see
• People may blame behaviour changes on other things, like school stress or a growth phase, before they think of the medicine
• A child's brain is still developing, so it may be more sensitive when leukotriene receptors are blocked in the central nervous system (the brain and spinal cord)

What to watch for in children:

• Nightmares or night terrors: a worry that parents often report
• New bedwetting in children who were previously dry
• Behaviour changes: more aggression, defiance or emotional outbursts that are not like them
• Anxiety or fearfulness: new fears, clinginess or not wanting to go to school
• Trouble sleeping: finding it hard to fall asleep, or waking often
• Mood changes: unusual sadness, tearfulness or losing interest in activities

Practical advice for parents:

• Start montelukast when you can watch your child closely for 2 to 4 weeks
• Keep a short daily diary of mood, behaviour and how well they sleep
• Tell teachers and childminders that your child has started the medicine, so they can report any changes they see
• Contact your GP if troublesome effects appear. In most cases, symptoms clear up within days of stopping the medicine

NICE guidance for paediatric asthma (the BTS/SIGN 2019 guideline) lists montelukast as an add-on option at steps 2 and 3 of the treatment ladder.

It weighs up both the benefits and the neuropsychiatric risk.

Montelukast can cause allergic and skin reactions, though these are uncommon. It helps to know the signs.

Skin reactions:

• Urticaria (hives): itchy, raised welts on the skin
• Pruritus: itching all over without a visible rash
• Eczema flare-up: some people find their eczema gets worse
• 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 needs medical help right away
• Anaphylaxis: a very rare but life-threatening allergic reaction. Signs include trouble breathing, a widespread rash, a fast pulse and collapse. Call 999 at once

Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis):

This is a rare type of vasculitis (inflamed blood vessels). It has been reported in people taking montelukast, mostly when oral steroid tablets are being reduced. Signs include:

• Asthma that gets worse
• Numbness or tingling in the hands and feet
• Skin rash
• Flu-like symptoms with a fever
• Sinusitis

Experts still debate the link between montelukast and Churg-Strauss syndrome. The condition may already have been there and only show up as steroids are cut back.

So montelukast may not be the direct cause. The BNF advises staying alert to it and checking out any signs of vasculitis affecting the whole body.

Liver effects:

Raised liver enzymes have been reported rarely. Very rarely, hepatitis (liver inflammation) and liver failure have happened.

Tell your prescriber about any unexplained nausea, tiredness, dark urine or jaundice (yellow skin or eyes).

Most people take montelukast without trouble. If you do get side effects, there are practical ways to deal with them.

For headache:

• A simple painkiller such as paracetamol is usually enough
• Headaches often settle within the first 1 to 2 weeks of treatment
• Drink plenty of fluids

For stomach and gut symptoms:

• Taking montelukast with food may ease stomach discomfort
• Symptoms are usually mild and short-lived

For sleep problems:

• Think about when you take the dose. Montelukast is usually taken in the evening. But if nightmares or poor sleep are a problem, taking it in the morning may help (though this is based on patient reports, not formal studies)
• Keep good sleep habits: a regular bedtime, a dark room, and no screens before bed
• If nightmares carry on, talk to your prescriber about stopping the medicine

For neuropsychiatric effects:

• These usually clear up within days to weeks of stopping montelukast
• There is no proven way to tell in advance who will be affected
• If symptoms are mild, your prescriber may suggest watching them for a short time to see if they settle
• If symptoms are serious, such as depression, suicidal thoughts or severe behaviour changes, stop the medicine and get a medical review urgently

Alternatives to montelukast:

If you cannot tolerate montelukast, other options for asthma control include:

• Inhaled corticosteroids (the mainstay of asthma treatment)
• Long-acting beta-agonists (for example salmeterol, formoterol)
• Combination inhalers
• For allergic rhinitis: antihistamines and intranasal corticosteroid sprays (steroid nasal sprays)

NICE and BTS/SIGN guidelines set out step-by-step ways to manage asthma that do not rely on montelukast.

Montelukast has been available since 1998. That gives us over 25 years of real-world safety data.

Long-term use data:

• Clinical trials lasting up to 2 years have found no new safety concerns with long-term use
• The side effect profile at 12 months looks much like the one seen in short-term trials
• There is no sign of organ damage with long-term use at the recommended doses
• There is no sign of tolerance, so the medicine keeps working over time

Regular review:

• NICE advises reviewing asthma treatment regularly, at least once a year
• At each review, your prescriber should check whether you still need montelukast. If your asthma is well controlled, it may be worth trying to step down or stop it
• For allergic rhinitis, taking it only during your hay fever season may be enough, rather than all year round

Pregnancy and breastfeeding:

• The BNF says montelukast may be used in pregnancy if the likely benefit outweighs the risk
• There is limited human data, but animal studies have shown no birth defects
• Small amounts of montelukast pass into breast milk, so ask a specialist for advice

Drug interactions:

Montelukast has few drug interactions that matter:

• CYP3A4 inducers (for example phenytoin, rifampicin) may lower montelukast levels
• CYP2C8 inhibitors (for example gemfibrozil) may raise montelukast levels
• It is generally safe to use with inhaled corticosteroids, beta-agonists and antihistamines

Montelukast has a well-proven safety record for long-term use. The key is to watch for neuropsychiatric symptoms and act on them promptly.