Montelukast

Montelukast is an oral cysteinyl leukotriene receptor antagonist used as add-on controller therapy in asthma, for prevention of exercise-induced bronchoconstriction and in allergic rhinitis. It is not a reliever and does not treat acute attacks.

Classification. Leukotriene receptor antagonist.

Mechanism. Selective antagonist of the CysLT1 receptor, blocking leukotriene-mediated bronchoconstriction, mucus secretion, oedema and eosinophil recruitment.

Pharmacokinetics. Oral bioavailability about 64%. Highly protein bound. Metabolised mainly by CYP2C8 with minor CYP3A4 and CYP2C9. Half-life 3 to 6 hours. Faecal elimination.

Add-on, asthma (usually with an inhaled corticosteroid).

• Adults and adolescents from 15 years: 10 mg once daily in the evening.

• Children 6 to 14 years: 5 mg chewable once daily.

• Children 2 to 5 years: 4 mg chewable or granules once daily. Granules 4 mg are used from 6 months in some regions.

• Maximum is the single daily dose; doses are not repeated or increased.

Alternative first-line, mild asthma when an inhaled corticosteroid cannot be used. Same doses, noting that it is less effective than an inhaled corticosteroid.

Exercise-induced bronchoconstriction. 10 mg at least 2 hours before exercise in adults, and not repeated within 24 hours. Not used in addition to daily montelukast.

Allergic rhinitis. 10 mg once daily in adults, 5 mg from 6 years. Reserve for patients who cannot take or do not respond to intranasal corticosteroids and antihistamines, because of the neuropsychiatric risk.

Emergency. Not used.

Titration and loading. None.

Boxed-warning-level risk. Serious neuropsychiatric events, including agitation, aggression, depression, sleep disturbance, hallucinations and suicidal thoughts and behaviour. In some regions this appears as a boxed warning with restriction in allergic rhinitis.

Contraindications. Hypersensitivity. Chewable tablets contain phenylalanine, which is unsuitable in phenylketonuria.

Serious adverse effects. Neuropsychiatric events, eosinophilic granulomatosis with polyangiitis unmasked as systemic corticosteroid doses fall, hepatotoxicity (rare), hypersensitivity including angioedema.

Common adverse effects. Headache, abdominal pain, upper respiratory infection, sleep disturbance.

Interactions. Gemfibrozil strongly raises montelukast exposure through CYP2C8 inhibition. Rifampicin and phenobarbital lower exposure; monitor response, as no formal dose change is advised.

Common prescribing errors. Using it for an acute attack. Giving it as sole controller in persistent asthma. Not warning the patient or parents about mood and sleep changes.

Special groups.

• Pregnancy: acceptable if needed, with limited data. Breastfeeding: excreted in milk in small amounts; probably compatible.

• Children: counsel carers about behaviour and sleep changes.

• Older adults: no adjustment.

• Kidney impairment: no adjustment. Liver impairment: no adjustment in mild to moderate; no data in severe.

• East Africa: rifampicin-containing tuberculosis regimens lower exposure, so review control.

Formulations. Tablet 10 mg, chewable tablets 4 mg and 5 mg, granules 4 mg.

Administration. Once daily in the evening, with or without food. Granules may be given directly or mixed with a spoonful of cold soft food, and taken within 15 minutes.

Baseline. Asthma control score and a record of mood and sleep.

Monitoring. Control, reliever use, mood and sleep at each review. Liver tests if symptoms of hepatitis occur.

Stop and reduce rules. Stop for any neuropsychiatric symptom and review urgently. Stop and investigate for rash, neuropathy, eosinophilia or pulmonary infiltrates. Therapeutic drug monitoring is not used.

Referral and escalation. Refer urgently for suicidal thoughts. Refer for systemic vasculitis features.