Sumatriptan - Drug Monograph

Introduction

Sumatriptan is a selective serotonin (5-HT1B/1D) receptor agonist belonging to the triptan class of medications. It was the first triptan approved by the FDA in 1992 and remains a cornerstone in the acute treatment of migraine and cluster headaches. As a specific antimigraine agent, sumatriptan provides targeted relief of migraine symptoms through its unique mechanism of action on cranial blood vessels and sensory nerves.

Mechanism of Action

Sumatriptan exerts its therapeutic effects through selective agonism at serotonin (5-HT1B and 5-HT1D) receptors. This results in:

• Constriction of dilated cranial blood vessels
• Inhibition of pro-inflammatory neuropeptide release
• Reduction of trigeminal nerve transmission
• Decreased nociceptive signaling in the brainstem

The vasoconstrictive effect is particularly selective for the carotid arterial circulation, which spares coronary arteries at therapeutic doses but necessitates caution in patients with cardiovascular risk factors.

Indications

• Acute treatment of migraine with or without aura in adults
• Acute treatment of cluster headache episodes in adults

• Status migrainosus (in some clinical settings)
• Short-lasting unilateral neuralgiform headache attacks (under specialist supervision)

Dosage and Administration

• Tablets: 25mg, 50mg, or 100mg orally at migraine onset; may repeat in 2 hours if needed (maximum 200mg/24h)
• Subcutaneous injection: 6mg SC; may repeat in 1 hour (maximum 12mg/24h)
• Nasal spray: 5mg, 10mg, or 20mg intranasally; may repeat in 2 hours (maximum 40mg/24h)

• Hepatic impairment: Maximum oral dose 50mg
• Renal impairment: No adjustment needed
• Elderly: Use with caution due to increased cardiovascular risk
• Pediatric: Not recommended under age 18

Pharmacokinetics

• Oral: Bioavailability ~15% (extensive first-pass metabolism)
• SC: Bioavailability ~97% (Tmax 10-12 minutes)
• Nasal: Bioavailability ~17% (Tmax 1-1.5 hours)

• Volume of distribution: 2.4 L/kg
• Protein binding: 14-21%
• Crosses blood-brain barrier minimally

• Primarily hepatic via monoamine oxidase-A (MAO-A)
• Forms inactive metabolites

• Half-life: ~2.5 hours
• Renal excretion: ~38% (mostly as metabolites)
• Fecal excretion: ~22%

Contraindications

• Ischemic heart disease or history of myocardial infarction
• Coronary artery vasospasm (Prinzmetal's angina)
• Uncontrolled hypertension
• Cerebrovascular syndromes
• Peripheral vascular disease
• Hemiplegic or basilar migraine
• Severe hepatic impairment
• Within 24 hours of another triptan or ergotamine-containing medication
• Hypersensitivity to sumatriptan or any component

Warnings and Precautions

• May cause coronary artery vasospasm, transient ECG changes
• Perform cardiovascular evaluation in patients with multiple risk factors
• Monitor for chest pain, shortness of breath, irregular heartbeat

• Rare reports of stroke and subarachnoid hemorrhage
• Discontinue if neurological symptoms develop

• Risk increased with concomitant serotonergic drugs
• Monitor for agitation, hallucinations, tachycardia, hyperthermia

• Medication overuse headache with frequent use (>10 days/month)
• Sudden withdrawal in dependent patients may cause rebound headache
• Use cautiously in patients with epilepsy or structural brain lesions

Drug Interactions

• MAO inhibitors: Contraindicated (increases sumatriptan levels 2-fold)
• Other 5-HT1 agonists: Additive vasoconstriction risk
• Ergot derivatives: Prolonged vasospastic reactions
• SSRIs/SNRIs: Increased serotonin syndrome risk
• CYP450 inhibitors: Potential increased sumatriptan exposure

Adverse Effects

• Injection site reactions (59%)
• Dizziness (12%)
• Somnolence (5-10%)
• Paresthesia (5-14%)
• Chest tightness/pressure (5-7%)
• Neck pain/stiffness (5-7%)

• Myocardial ischemia/infarction
• Cerebrovascular events
• Arrhythmias
• Severe hypersensitivity reactions
• Seizures
• Serotonin syndrome

Monitoring Parameters

• Cardiovascular assessment
• Blood pressure
• Medication history (serotonergic agents)
• Headache frequency and characteristics

• Headache response and recurrence
• Adverse effects (particularly cardiovascular)
• Frequency of use (prevent medication overuse)
• Blood pressure in hypertensive patients
• Signs of serotonin syndrome

• Headache diary to assess efficacy and patterns
• Cardiovascular status in at-risk patients
• Liver function tests with chronic use

Patient Education

• Use at first sign of migraine for best results
• Do not exceed recommended dosage frequency
• Seek immediate medical attention for chest pain, shortness of breath, or neurological symptoms
• Avoid driving or operating machinery if drowsiness occurs
• Do not use for more than 10 headache days per month
• Inform all healthcare providers of sumatriptan use
• Store injection and nasal spray at room temperature
• Report any unusual side effects promptly
• Consider keeping a headache diary to track effectiveness

References

1. Goadsby PJ, et al. Sumatriptan: a review of its pharmacology and therapeutic efficacy in the acute treatment of migraine. Drugs. 2022;82(1):61-85. 2. FDA Prescribing Information: Imitrex (sumatriptan). 2023. 3. Dodick DW. Acute and preventive treatment of migraine. Continuum (Minneap Minn). 2021;27(3):597-612. 4. Tepper SJ. Safety and rational use of sumatriptan. Headache. 2019;59(8):1229-1236. 5. Johnston MM, et al. Triptans in the acute treatment of migraine: a systematic review and network meta-analysis. Headache. 2021;61(1):100-112. 6. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18.