Introduction
Imitrex (sumatriptan) is a selective serotonin receptor agonist specifically developed for the acute treatment of migraine and cluster headache attacks. As the first triptan medication approved by the FDA in 1991, it revolutionized migraine therapy by providing targeted relief for moderate to severe migraine attacks with or without aura.
Mechanism of Action
Sumatriptan selectively binds to serotonin (5-HT1B/1D) receptors, causing cranial vessel constriction, inhibiting neuropeptide release, and reducing pain transmission in the trigeminal pathway. It reverses the vasodilation of meningeal blood vessels that occurs during migraine attacks and reduces the release of inflammatory mediators from trigeminal nerve endings.
Indications
- Acute treatment of migraine with or without aura in adults
- Acute treatment of cluster headache episodes in adults
- Not indicated for migraine prophylaxis or routine use
Dosage and Administration
Tablets: 25 mg, 50 mg, or 100 mg orally at onset of migraine; may repeat in 2 hours if needed (max 200 mg/24h) Nasal Spray: 5 mg, 10 mg, or 20 mg single dose in one nostril; may repeat in 2 hours (max 40 mg/24h) Subcutaneous Injection: 4 mg or 6 mg single injection; may repeat in 1 hour (max 12 mg/24h) Special Populations:- Hepatic impairment: Use lower doses with caution
- Renal impairment: No dosage adjustment needed for mild-moderate impairment
- Elderly: Consider starting with lower doses
- Pediatrics: Not recommended under age 18
Pharmacokinetics
Absorption: Oral bioavailability ~15% (extensive first-pass metabolism); subcutaneous bioavailability ~97% with Tmax of 10-15 minutes Distribution: Volume of distribution ~2.4 L/kg; 14-21% protein bound Metabolism: Primarily metabolized by monoamine oxidase-A (MAO-A) to inactive metabolites Elimination: Half-life ~2 hours; primarily renal excretion (60%) with some fecal eliminationContraindications
- Ischemic heart disease or history of myocardial infarction
- Coronary artery vasospasm (Prinzmetal's angina)
- Uncontrolled hypertension
- Cerebrovascular syndromes
- Peripheral vascular disease
- History of stroke or TIA
- Severe hepatic impairment
- Within 24 hours of ergotamine-containing medications
- Within 24 hours of another 5-HT1 agonist
- Hypersensitivity to sumatriptan
Warnings and Precautions
- Cardiac events: May cause coronary artery vasospasm, myocardial ischemia, or infarction
- Chest pain/symptoms: Requires immediate medical evaluation if occurring
- Serotonin syndrome: Risk when used with other serotonergic drugs
- Cerebrovascular events: Reports of stroke and hemorrhage
- Medication overuse headache: May occur with frequent use (>10 days/month)
- Sensitivity reactions: Anaphylaxis/anaphylactoid reactions reported
- Seizures: Use cautiously in patients with epilepsy
- Pregnancy: Category C - use only if potential benefit justifies risk
Drug Interactions
- Ergot derivatives: Increased risk of vasospasm (contraindicated within 24 hours)
- MAO inhibitors: Increased sumatriptan concentrations (contraindicated)
- Other triptans: Additive vasoconstrictive effects (avoid within 24 hours)
- SSRIs/SNRIs: Increased risk of serotonin syndrome
- CYP450 inhibitors: May increase sumatriptan exposure
Adverse Effects
Common (≥2%):- Injection site reactions (59%)
- Atypical sensations (tingling, warmth, pressure)
- Dizziness/vertigo (12%)
- Flushing (7%)
- Chest/neck/jaw pressure (5%)
- Fatigue (5%)
- Nasal spray: Taste disturbance, nasal discomfort
- Coronary artery vasospasm
- Myocardial infarction
- Arrhythmias
- Cerebral hemorrhage
- Stroke
- Bowel ischemia
- Serotonin syndrome
- Seizures
Monitoring Parameters
- Blood pressure and heart rate at baseline and periodically
- Cardiac status in patients with risk factors
- Frequency of migraine attacks and medication use
- Signs of serotonin syndrome
- Signs of medication overuse headache
- Neurological status
- Renal and hepatic function in impaired patients
Patient Education
- Use only at onset of migraine symptoms, not for prophylaxis
- Maximum dosing frequency: No more than 2 doses in 24 hours
- Do not use more than 10 days per month to prevent medication overuse headache
- Seek immediate medical attention for chest pain, shortness of breath, or severe neurological symptoms
- Report any unusual sensations or side effects
- Avoid driving or operating machinery if drowsy or dizzy
- Inform all healthcare providers of sumatriptan use
- Store at room temperature, protect from light
- Proper injection technique training if using subcutaneous form
References
1. FDA Prescribing Information: Imitrex (sumatriptan) 2. Goadsby PJ, et al. Migraine: current understanding and treatment. N Engl J Med. 2002 3. Tepper SJ. Safety and rational use of the triptans. Med Clin North Am. 2013 4. Dodick DW. Triptans and serotonin syndrome. Cephalalgia. 2004 5. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019 6. UpToDate: Sumatriptan drug information 7. Micromedex: Sumatriptan therapeutic monograph 8. Clinical Pharmacology: Sumatriptan prescribing information