Zolmitriptan

Zolmitriptan is a selective serotonin (5-HT1B/1D) receptor agonist, a triptan, used for the acute treatment of migraine headaches, with or without aura. It is available in the UK in several formulations: standard tablets (2.5mg and 5mg), orodispersible tablets (2.5mg), and a nasal spray (5mg). It is marketed under the brand name Zomig.

Mechanism of Action

During a migraine, the trigeminal nerve system becomes activated, triggering dilation of intracranial blood vessels, release of neuropeptides such as calcitonin gene-related peptide (CGRP), and transmission of pain signals to the brain. Zolmitriptan acts at 5-HT1B receptors on the smooth muscle of cranial blood vessels to cause vasoconstriction, reversing pathological vasodilation. It also acts at 5-HT1D receptors on peripheral trigeminal nerve terminals and in the trigeminal nucleus caudalis in the brainstem, inhibiting the release of pro-inflammatory neuropeptides and blocking central pain transmission.

This dual peripheral and central action makes zolmitriptan effective not only for headache pain but also for associated symptoms such as nausea, phonophobia, and photophobia.

Onset and Duration

Zolmitriptan begins to relieve migraine symptoms within 30 to 45 minutes of oral administration. The nasal spray formulation has a faster onset than tablets in some patients. Pain relief or freedom from pain is typically achieved within two hours in the majority of responders.

When to Use Zolmitriptan

Zolmitriptan should be taken as early as possible during the headache phase of a migraine. It is not effective if taken during the prodrome or aura phase before headache onset. It is not a preventative medicine and should not be taken daily to prevent migraines, as this can lead to medication overuse headache (MOH).

Zolmitriptan should be taken at the first sign of a migraine headache, not during the prodrome or aura phase. The recommended starting dose is 2.5mg. If headache returns after initial relief, a second dose may be taken at least two hours after the first, up to a maximum of 10mg in any 24-hour period.

Formulation-Specific Instructions

For standard tablets, swallow whole with water. For orodispersible tablets (Zomig Rapimelt), place on the tongue and allow it to dissolve, no water is needed, making these particularly useful during nausea. For the nasal spray, blow the nose before use, insert the nozzle into one nostril, and depress the plunger firmly once. Do not sniff or inhale, allow the spray to be absorbed through the nasal mucosa.

Frequency of Use

Triptans should not be used on more than 10 days per month. Using any acute headache treatment on more than 10-15 days per month for three or more months risks the development of medication overuse headache, a paradoxical condition in which the medicine itself perpetuates daily or near-daily headache.

Zolmitriptan standard dosing:

• Tablets or orodispersible tablets: 2.5mg at headache onset; may repeat after 2 hours if headache returns; maximum 10mg in 24 hours.
• Nasal spray (5mg per actuation): one spray at onset; may repeat after 2 hours if needed; maximum 10mg (two sprays) in 24 hours.

In hepatic impairment: maximum dose 5mg per 24-hour period. Not recommended in severe hepatic impairment. No dose adjustment is required for mild to moderate renal impairment. Not recommended in children under 12.

Common Side Effects

• Tingling or paraesthesia (pins and needles in the extremities)
• Warmth, heaviness, or tightness in the chest, neck, or jaw
• Dizziness
• Dry mouth
• Nausea
• Muscle weakness
• Nasal irritation or bad taste (nasal spray formulation)

Serious Side Effects

• Coronary vasospasm: chest pain or tightness, stop and seek emergency care if prolonged or severe
• Serotonin syndrome (when combined with SSRIs/SNRIs): agitation, tremor, rapid heart rate
• Ischaemic stroke or TIA (rare, particularly in patients with cardiovascular risk factors)
• Severe hypertension: particularly in patients with undiagnosed hypertension or peripheral vascular disease

Zolmitriptan should only be used to treat confirmed migraine. It should not be used for hemiplegic migraine, basilar migraine, or in patients who have not had their headache formally diagnosed by a doctor, as triptans are not appropriate for tension-type headache or secondary headache disorders.

Cardiovascular Precautions

Because zolmitriptan causes vasoconstriction, it is contraindicated in patients with ischaemic heart disease, previous myocardial infarction, coronary artery vasospasm, peripheral vascular disease, or previous stroke or TIA. The medicine should be used with caution in patients with significant cardiovascular risk factors even if overt disease has not been diagnosed.

Drug Interactions

Concurrent use of monoamine oxidase inhibitors (MAOIs) is contraindicated. The maximum dose should be halved when cimetidine is used concurrently. Use alongside other serotonergic medicines (SSRIs, SNRIs, other triptans) requires caution and awareness of serotonin syndrome symptoms. Medication overuse headache is a significant risk if zolmitriptan is used more than 10 days per month.

• Ischaemic heart disease, angina, or previous myocardial infarction
• Coronary artery vasospasm (Prinzmetal's angina)
• Peripheral vascular disease
• Previous stroke or transient ischaemic attack (TIA)
• Uncontrolled hypertension
• Hemiplegic or basilar migraine
• Concurrent or recent (within 2 weeks) use of MAOIs
• Concurrent use of other triptans or ergotamine derivatives
• Severe hepatic impairment
• Hypersensitivity to zolmitriptan or any excipient