Sumatriptan

Generic Name

Sumatriptan succinate

Brand Names

Imitrex

Imigran

Treximet (with naproxen sodium)

Sumavel DosePro

Zembrace SymTouch

Onzetra Xsail

Tosymra

Others vary by region and formulation

Drug Class

Selective 5-HT₁B/1D receptor agonist

Triptan class

Antimigraine agent

Vasoconstrictor

Mechanism of Action

Sumatriptan is a serotonin receptor agonist that selectively binds to the 5-hydroxytryptamine (5-HT) subtype 1B and 1D receptors located on intracranial blood vessels and sensory nerve endings of the trigeminal system

Stimulation of 5-HT₁B receptors causes vasoconstriction of dilated cranial arteries

Stimulation of 5-HT₁D receptors inhibits pro-inflammatory neuropeptide release from trigeminal nerves

Sumatriptan also inhibits transmission of pain signals in the trigeminal nucleus caudalis

It does not affect peripheral arteries significantly and lacks activity at 5-HT₂ or dopamine receptors

Indications

Approved Uses

Acute treatment of migraine attacks with or without aura in adults and children ≥6 years (age cutoffs vary by formulation)

Acute treatment of cluster headache in adults (subcutaneous formulation only)

Off-label Uses

Short-term treatment of menstrual migraines

Post-dural puncture headache (in select cases)

Acute attacks of paroxysmal hemicrania (as bridge or rescue therapy)

Dosage and Administration

Oral Tablets

Usual adult dose: 50 mg or 100 mg orally at onset of migraine

Range: 25–100 mg

If symptoms recur, one repeat dose may be given after at least 2 hours

Maximum: 200 mg per 24 hours

Pediatric (≥6 years): weight-based dosing, often 25–50 mg under specialist supervision

Subcutaneous Injection (Zembrace, Sumavel)

6 mg subcutaneously once at onset of headache

May repeat after ≥1 hour if needed

Maximum: 12 mg per 24 hours

Effective for cluster headaches

Nasal Spray (Imigran, Tosymra)

5 mg, 10 mg, or 20 mg per actuation

One spray in one nostril at onset

May repeat after ≥2 hours

Maximum: 40 mg per 24 hours

Nasal Powder (Onzetra Xsail)

11 mg (delivers 22 mg total) via Xsail device

May repeat in 2 hours

Maximum: 44 mg per 24 hours

Oral with NSAID (Treximet)

85 mg sumatriptan + 500 mg naproxen sodium

One tablet at onset

May repeat in 2 hours

Maximum: two tablets per 24 hours

Route of Administration

Available in oral, subcutaneous, nasal spray, and nasal powder forms

Choose based on severity, nausea/vomiting, speed of onset, and patient preference

Pharmacokinetics

Absorption

Oral bioavailability ~15% due to first-pass metabolism

Subcutaneous provides rapid absorption with peak concentration in ~10 minutes

Nasal spray onset ~15 minutes

Onzetra and Tosymra designed for faster or targeted delivery

Distribution

Volume of distribution: 2.4 L/kg

Low plasma protein binding ~14–21%

Metabolism

Extensively metabolized by monoamine oxidase A (MAO-A)

Inactive metabolites

Not metabolized by CYP450 enzymes

Elimination

Primarily via urine (60%) and feces (40%)

Half-life: ~2 hours (short, limits duration of action)

Cleared rapidly; requires second dose if recurrence occurs

Contraindications

Ischemic heart disease (angina, MI)

History of stroke or TIA

Peripheral vascular disease

Uncontrolled hypertension

Hemiplegic or basilar migraine

Use within 24 hours of another triptan or ergotamine-containing drug

Severe hepatic impairment

MAOI use within 2 weeks

Hypersensitivity to sumatriptan or formulation ingredients

Warnings and Precautions

Cardiovascular Risk

Reports of coronary vasospasm, myocardial infarction, ventricular arrhythmias, and sudden death

Avoid in patients with cardiovascular disease

ECG recommended in those with risk factors or atypical symptoms

Cerebrovascular Events

Stroke and subarachnoid hemorrhage have been reported

Avoid in patients with cerebrovascular disease

Serotonin Syndrome

Risk increased when used with SSRIs, SNRIs, MAOIs, or other serotonergic agents

Monitor for agitation, hallucinations, tachycardia, hyperreflexia, and fever

Medication Overuse Headache (MOH)

Excessive use (>10 days/month) can lead to rebound headaches

Encourage limited, targeted use

Seizures

Rare cases reported even in patients without epilepsy

Use caution in seizure-prone individuals

Hypersensitivity Reactions

Anaphylaxis, angioedema, and rash reported

Discontinue if allergic reaction occurs

Injection Site Reactions

Common with subcutaneous form, including pain, redness, or swelling

Vision Changes

Blurred vision or transient loss of vision reported

Pregnancy Category

US: Not formally assigned (previously Category C)

Use only if potential benefit outweighs fetal risks

Limited data suggest low risk in human pregnancy

Avoid routine use

Lactation

Excreted in breast milk

Minimal systemic absorption by infant expected

Pump and discard for 12 hours after use to minimize exposure

Pediatrics

Approved for children ≥6 years (tablets) and ≥12 years (nasal spray) in some regions

Used off-label in younger children by specialists

Geriatrics

Limited data

Increased cardiovascular risk necessitates caution

Assess for contraindications before use

Adverse Effects

Very Common

Tingling

Flushing

Warmth or cold sensation

Fatigue

Dizziness

Chest tightness (non-cardiac)

Injection site reactions (if subcutaneous)

Common

Nausea

Throat discomfort

Heaviness in limbs

Drowsiness

Transient increase in blood pressure

Muscle pain

Less Common

Arrhythmias

Visual disturbances

Anxiety

Seizures

Anaphylaxis

Ischemic colitis

Rare and Serious

Myocardial infarction

Stroke

Ventricular fibrillation

Angioedema

Serotonin syndrome

Overdose

Symptoms

Hypertension

Tremor

Ataxia

Cyanosis

Loss of coordination

Seizures

Management

No antidote

Supportive care with ECG monitoring

Avoid repeated doses after overdose

Dialysis not effective

Drug Interactions

MAO-A inhibitors

Inhibit metabolism of sumatriptan

Avoid concurrent use and for 14 days post MAOI

SSRIs/SNRIs/TCA

Increased risk of serotonin syndrome

Monitor closely

Ergot derivatives (ergotamine, dihydroergotamine)

Vasoconstriction risk increased

Avoid within 24 hours of each other

Other triptans

Avoid use within 24 hours of another triptan to reduce additive vasoconstriction

Linezolid and methylene blue

Serotonin toxicity risk

Avoid co-administration

Propranolol

Increases plasma levels of sumatriptan slightly

May enhance therapeutic effects

CYP interactions

Negligible since sumatriptan is not metabolized by CYP450

Use in Special Populations

Renal impairment

No specific adjustment necessary but monitor response

Hepatic impairment

Use with caution in mild to moderate impairment

Avoid in severe hepatic dysfunction

Comparative Pharmacology

Sumatriptan vs rizatriptan

Rizatriptan has slightly faster onset and longer half-life

Sumatriptan available in more delivery forms

Sumatriptan vs zolmitriptan

Both effective for migraines

Zolmitriptan has better CNS penetration

Sumatriptan preferred for cluster headache (injectable form)

Sumatriptan vs ergotamine

Sumatriptan more selective and better tolerated

Ergotamine has more adverse cardiovascular and GI effects

Sumatriptan vs NSAIDs

Triptans more effective for migraine resolution

NSAIDs better for menstrual migraine or mild attacks

Formulations Available

Oral tablets: 25 mg, 50 mg, 100 mg

Subcutaneous injection: 6 mg/0.5 mL prefilled syringe or autoinjector

Nasal spray: 5 mg, 10 mg, 20 mg

Nasal powder (Xsail): 11 mg per nosepiece

Combination tablet (Treximet): 85 mg sumatriptan + 500 mg naproxen sodium

Storage

Store at room temperature

Protect injectable and nasal products from light and moisture

Regulatory and Legal Status

Prescription-only

Approved by FDA, EMA, MHRA, and other global health authorities

First triptan introduced in 1991

Included in WHO Model List of Essential Medicines