Sumatriptan

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Sumatriptan is a selective serotonin (5-HT1B/1D) receptor agonist, commonly referred to as a triptan, and is the most widely used acute migraine treatment in the United Kingdom.

First licensed in 1991, sumatriptan transformed the management of migraine by providing the first mechanism-targeted therapy for acute attacks.

It is available as oral tablets (50 mg and 100 mg), a nasal spray (10 mg and 20 mg), and a subcutaneous injection (6 mg auto-injector).

Sumatriptan 50 mg tablets are available from pharmacies as a pharmacy medicine (P) for adults aged 18 to 65 with a previously diagnosed migraine; all other formulations and the 100 mg tablet are prescription-only medicines (POM).

Migraine affects approximately 10 million people in the UK and is ranked by the World Health Organization as one of the most disabling conditions worldwide.

It is characterised by recurrent episodes of moderate to severe unilateral throbbing headache, often accompanied by nausea, vomiting, photophobia (sensitivity to light), and phonophobia (sensitivity to sound).

Migraine attacks last between 4 and 72 hours and can be profoundly debilitating, affecting work, social functioning, and quality of life.

This page provides a comprehensive clinical overview of sumatriptan, including how it works, the evidence supporting its use, formulation options, dosing, side effects, safety warnings, and how to obtain it in the UK.

Important safety information about sumatriptan

Before reading further, note the following key safety points about sumatriptan.

• Sumatriptan treats acute migraine attacks. It does not prevent migraines or reduce their frequency.
• Do not use sumatriptan if you have a history of heart disease, stroke, uncontrolled high blood pressure, or peripheral vascular disease.
• Do not take sumatriptan within 24 hours of using ergotamine or another triptan.
• Using sumatriptan on 10 or more days per month can cause medication-overuse headache. If this applies to you, discuss preventive treatment with your GP.

What is migraine

Migraine is a complex neurological condition with a strong genetic basis, involving abnormal activation of the trigeminovascular system.

The current understanding is that migraine begins with cortical neuronal hyperexcitability, which in susceptible individuals triggers cortical spreading depression (CSD), a wave of neuronal depolarisation that spreads across the cortex and is responsible for the visual and sensory phenomena of migraine aura.

CSD activates meningeal trigeminal afferents, causing the release of vasoactive neuropeptides, particularly calcitonin gene-related peptide (CGRP), substance P, and neurokinin A.

These neuropeptides cause dilation of meningeal blood vessels, extravasation of plasma proteins, and neurogenic inflammation, which sensitises peripheral and central pain pathways, producing the characteristic throbbing headache.

Migraine without aura accounts for approximately 70 to 80% of all migraine attacks.

Migraine with aura, characterised by transient focal neurological symptoms (most commonly visual disturbance such as scintillating scotoma or fortification spectra) preceding or accompanying the headache, accounts for approximately 20 to 30%.

Less common subtypes include hemiplegic migraine (with temporary motor weakness), basilar migraine (with brainstem symptoms), and chronic migraine (headache on 15 or more days per month, of which at least 8 days have migraine features).

How sumatriptan works: mechanism of action

Sumatriptan is a selective agonist at two serotonin receptor subtypes: 5-HT1B and 5-HT1D. These receptors are concentrated on intracranial blood vessels and on trigeminal nerve terminals, making sumatriptan highly targeted to the pathological processes driving migraine pain.

Cranial vasoconstriction (5-HT1B)

Activation of 5-HT1B receptors on the smooth muscle of dilated intracranial arteries and meningeal vessels causes vasoconstriction, reversing the pathological vasodilation that contributes to the throbbing quality of migraine headache.

This effect is selective for cranial vessels; sumatriptan has minimal effect on peripheral or coronary vasculature at therapeutic doses, although coronary vasoconstriction is possible and underlies the cardiovascular contraindications.

Inhibition of neuropeptide release (5-HT1D)

Activation of presynaptic 5-HT1D receptors on trigeminal nerve endings inhibits the release of CGRP, substance P, and other pro-inflammatory neuropeptides. This reduces neurogenic inflammation and meningeal vasodilation and is considered the primary mechanism of action of sumatriptan in migraine.

Central pain pathway modulation

Sumatriptan may also act at 5-HT1B/1D receptors in the trigeminal nucleus caudalis in the brainstem, inhibiting the central relay of nociceptive (pain) signals from the meninges to higher cortical centres.

This central action contributes to the relief of associated symptoms such as nausea, photophobia, and phonophobia.

Clinical evidence for sumatriptan

Sumatriptan has been evaluated in over 300 clinical trials since its introduction.

The pivotal registration trials demonstrated that oral sumatriptan 50 mg and 100 mg produced headache relief (reduction from moderate or severe pain to mild or no pain at 2 hours) in approximately 50 to 60% and 55 to 65% of patients, respectively, compared with 25 to 35% for placebo.

Pain-free at 2 hours was achieved in approximately 25 to 30% with 50 mg and 30 to 35% with 100 mg.

A Cochrane systematic review of oral sumatriptan for acute migraine (Derry et al.) confirmed that sumatriptan is significantly more effective than placebo for headache relief and pain-free outcomes and also relieves associated symptoms (nausea, photophobia, phonophobia).

The number needed to treat (NNT) for one additional patient to achieve pain-free at 2 hours was approximately 6 for 50 mg and 5 for 100 mg compared with placebo.

The subcutaneous injection provides the fastest onset (within 10 to 15 minutes) and highest response rates, with approximately 70 to 80% of patients achieving headache relief at one hour.

The nasal spray has an intermediate onset and is useful for patients with nausea or vomiting who cannot reliably absorb oral medication.

Sumatriptan combined with naproxen

A fixed-dose combination of sumatriptan 85 mg and naproxen 500 mg has been shown in clinical trials to be more effective than either drug alone for acute migraine.

NICE Clinical Knowledge Summaries recommend considering the combination of a triptan with an NSAID for patients who do not respond adequately to either agent alone.

In UK practice, this combination is typically achieved by taking sumatriptan and naproxen as separate tablets, as the fixed-dose combination product is not widely available.

Formulation options

Oral tablets

The most commonly used formulation. Available as 50 mg and 100 mg tablets. The 50 mg dose is the standard starting dose for most adults.

The 100 mg dose may be used if 50 mg provides insufficient relief. Onset of action is typically 30 to 60 minutes.

The bioavailability is approximately 14%, as sumatriptan undergoes extensive first-pass metabolism by monoamine oxidase A (MAO-A) in the liver.

Nasal spray

Available as 10 mg and 20 mg single-dose devices. The 20 mg dose is recommended for most adults. Onset of action is approximately 15 to 30 minutes.

Part of the dose is absorbed directly through the nasal mucosa, bypassing first-pass metabolism, while a proportion is swallowed and absorbed from the gastrointestinal tract.

The nasal spray is the only licensed sumatriptan formulation for adolescents aged 12 to 17 years (10 mg dose). An unpleasant taste is a common complaint.

Subcutaneous injection

Available as a 6 mg single-dose auto-injector. The injection provides the fastest onset (10 to 15 minutes) and highest efficacy, with a bioavailability of approximately 96%.

It is particularly useful for patients with severe nausea or vomiting, rapidly escalating migraine, or cluster headache. Injection site reactions (pain, redness, swelling) are common but transient.

The subcutaneous injection is the only sumatriptan formulation licensed for cluster headache in the UK.

Sumatriptan for cluster headache

Cluster headache is a primary headache disorder characterised by severe, strictly unilateral periorbital or temporal pain lasting 15 to 180 minutes, occurring in clusters of daily or near-daily attacks over weeks to months.

It is associated with ipsilateral autonomic features including lacrimation, conjunctival injection, nasal congestion, and ptosis.

Cluster headache predominantly affects men and is sometimes called "suicide headache" due to the severity of pain.

Subcutaneous sumatriptan 6 mg is the most effective acute treatment for cluster headache, with pain relief achieved in approximately 75% of patients within 15 minutes.

NICE and the British Association for the Study of Headache (BASH) guidelines recommend subcutaneous sumatriptan as first-line acute treatment alongside high-flow oxygen (100%, 12 to 15 litres per minute via a non-rebreather mask).

Intranasal sumatriptan 20 mg is an alternative for patients who cannot self-inject.

Over-the-counter availability in the UK

Sumatriptan 50 mg tablets were reclassified from POM to P (pharmacy medicine) in 2006, allowing supply by pharmacists without a prescription under specific conditions.

The pharmacist must confirm that the patient has a previously established diagnosis of migraine (made by a doctor), that the patient is aged 18 to 65, that there are no cardiovascular or other contraindications, and that no interacting medicines are being taken.

A maximum of two tablets may be supplied per transaction. This reclassification has improved access to effective migraine treatment and reduced unnecessary GP consultations for acute migraine episodes.

Side effects of sumatriptan

Common side effects

Tingling, warmth, flushing, heaviness, and pressure or tightness sensations (including chest and throat tightness) are the most commonly reported effects and are triptan class phenomena.

They are usually transient (lasting less than one hour) and not indicative of cardiac ischaemia. Dizziness, drowsiness, nausea, and fatigue are also common.

Injection-site reactions

Pain, swelling, redness, and bruising at the injection site are very common with the subcutaneous formulation but resolve rapidly.

Serious side effects

Coronary artery vasospasm is rare but can cause angina or myocardial infarction. It is almost exclusively reported in patients with pre-existing cardiovascular disease or multiple cardiovascular risk factors.

Serotonin syndrome, seizures, and anaphylaxis are very rare. Medication-overuse headache is an important iatrogenic complication of frequent triptan use.

When to seek urgent medical advice

Seek emergency help (call 999 or attend A&E) if you experience severe or prolonged chest pain after taking sumatriptan, sudden weakness on one side of the body, difficulty speaking, facial drooping (possible stroke symptoms), signs of serotonin syndrome (agitation, confusion, high temperature, rapid heartbeat, tremor), or a severe allergic reaction (swelling of the face, lips, or throat, difficulty breathing).

Contact your GP or NHS 111 for non-urgent concerns including a change in your headache pattern, increased frequency of migraine attacks, or side effects that are persistent or troublesome.

Report any suspected adverse reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk .

Warnings and precautions

Cardiovascular contraindications

Sumatriptan is contraindicated in patients with established ischaemic heart disease, previous myocardial infarction, coronary vasospasm (Prinzmetal angina), peripheral vascular disease, cerebrovascular disease (previous stroke or TIA), and uncontrolled hypertension.

Patients with multiple cardiovascular risk factors should undergo cardiovascular assessment before first use.

Drug interactions

Do not take sumatriptan within 24 hours of ergotamine or another triptan. Do not use with MAOIs or within 2 weeks of stopping an MAOI.

Use cautiously with SSRIs, SNRIs, and other serotonergic medicines due to the risk of serotonin syndrome.

Medication-overuse headache

Using sumatriptan or any acute headache medication on 10 or more days per month can lead to a cycle of chronic daily headache and medication overuse.

If this is suspected, a structured withdrawal under medical supervision may be necessary before effective preventive treatment can be established.

How to get sumatriptan in the UK

Sumatriptan 50 mg tablets can be purchased from a pharmacy without a prescription (P medicine) for adults aged 18 to 65 with a confirmed migraine diagnosis.

The pharmacist will ask screening questions about your medical history and current medicines. Brand names available over the counter include Imigran Recovery and generic pharmacy brands.

Prescription-only formulations (100 mg tablets, nasal spray, and injection) are available from your GP on NHS prescription.

The standard NHS prescription charge in England is 9.90 pounds per item; prescriptions are free in Scotland, Wales, and Northern Ireland.

Sources

• Imigran 50 mg Tablets, Summary of Product Characteristics (EMC)
• Sumatriptan, British National Formulary (BNF)
• NICE CG150: Headaches in over 12s: diagnosis and management
• Sumatriptan, NHS
• Sumatriptan (oral route of administration) for acute migraine attacks in adults (Cochrane Review)
• MHRA Yellow Card Scheme