Zolmitriptan

Zolmitriptan is a triptan used for acute treatment of migraine, available as tablets, orally disintegrating tablets and nasal spray. It has an active metabolite, and its dose is limited by liver impairment and by drugs that inhibit its metabolism.

Mechanism. Serotonin 5-HT1B/1D receptor agonist that constricts cranial vessels and inhibits release of calcitonin gene-related peptide.

Pharmacokinetics. Bioavailability about 40% and half-life about 3 hours. It is metabolised by cytochrome P450 1A2 and monoamine oxidase A to an active N-desmethyl metabolite. Cimetidine doubles exposure, and fluvoxamine and ciprofloxacin raise it.

First-line use. Acute migraine attacks with or without aura.

• Oral zolmitriptan: 2.5 mg at onset (1.25 mg if a lower dose is preferred), repeated after at least 2 hours if migraine returns. A 5 mg dose may be used if 2.5 mg is not effective. Maximum 10 mg in 24 hours.

• Intranasal: 5 mg once, repeated after at least 2 hours. Maximum 10 mg in 24 hours.

• With cimetidine, fluvoxamine or ciprofloxacin: maximum 5 mg in 24 hours.

• Adolescents 12 to 17 years: intranasal use is licensed in some regions, under specialist advice.

Kidney, liver, weight and age.

• Kidney: no adjustment in mild to moderate impairment.

• Liver: moderate to severe impairment, start 1.25 mg and limit to 5 mg in 24 hours.

• Older adults: avoid over age 65 unless cardiovascular status is clear.

Contraindications. Ischaemic heart disease, previous myocardial infarction, coronary vasospasm, peripheral vascular disease, previous stroke or transient ischaemic attack, uncontrolled hypertension, Wolff-Parkinson-White syndrome and other pre-excitation arrhythmias, hemiplegic or basilar migraine, monoamine oxidase A inhibitors within 2 weeks, and ergotamine or another triptan within 24 hours.

Serious adverse effects. Myocardial infarction, coronary vasospasm, arrhythmia, stroke, hypertension, serotonin syndrome, and medication overuse headache.

Common adverse effects. Tingling, warmth, dizziness, somnolence, nausea, dry mouth, and throat or chest tightness.

Interactions. Cytochrome P450 1A2 inhibitors (cimetidine, fluvoxamine, ciprofloxacin) raise levels. Monoamine oxidase A inhibitors, ergot alkaloids and other triptans are contraindicated. Selective serotonin reuptake inhibitors and St John's wort add serotonin syndrome risk.

Common prescribing errors. Not reducing the maximum dose with cimetidine or ciprofloxacin. Use on more than 10 days each month. Prescribing in unrecognised vascular disease.

Special groups.

• Pregnancy: limited data; avoid unless clearly needed.

• Breastfeeding: use with caution.

• Phenylketonuria: orally disintegrating tablets contain phenylalanine.

Formulations. Tablets 2.5 and 5 mg. Orally disintegrating tablets 2.5 and 5 mg. Nasal spray 5 mg.

Monitoring.

• Baseline blood pressure and cardiovascular risk review.

• Headache diary, with acute treatment limited to under 10 days each month.

Stopping. No taper is needed.

Referral and escalation. Refer for poor response, frequent attacks, or suspected medication overuse headache.