What is Naratriptan?
Naratriptan is a selective serotonin (5-HT1B/1D) receptor agonist—a triptan medication—indicated for the acute treatment of migraine attacks with or without aura in adults. 1
Mechanism of Action
- Naratriptan works as a potent and selective agonist at 5-HT1B and 5-HT1D vascular receptors, which are the primary targets for migraine relief 2
- Unlike ergotamine compounds, naratriptan has no significant activity at 5HT2 receptors, which mediate coronary artery constriction, making it safer from a cardiac standpoint 3
Clinical Efficacy and Characteristics
- Oral naratriptan 2.5 mg (the standard marketed dose) demonstrates efficacy that becomes significant after 1 hour, reaches maximum effect at 4 hours, and persists for 24 hours 2
- Naratriptan has the longest half-life among triptans, which may decrease recurrence of headaches within 24 hours—a key advantage over other triptans 4, 2
- The standard oral dose reduces migraine recurrence by approximately 50% within 24 hours compared to other triptans 2
- Subcutaneous naratriptan has rapid absorption (peak concentration at 10 minutes) and demonstrates superior efficacy, with doses of 10 mg achieving 88-91% headache relief at 2 hours 5, 6
Dosing and Administration
- Standard oral dose: 1 mg or 2.5 mg at migraine onset 1
- May repeat dose after 4 hours if needed, but not to exceed 5 mg in any 24-hour period 1
- For patients with mild or moderate renal or hepatic impairment: start with 1 mg and do not exceed 2.5 mg in 24 hours 1
- Naratriptan is associated with a slower onset of action compared to other oral triptans like rizatriptan or subcutaneous sumatriptan, making it less ideal for rapidly progressing attacks 4
Safety Profile and Tolerability
- Naratriptan has an excellent tolerance profile, with the 2.5 mg dose producing no more adverse events than placebo 2
- Most common adverse reactions (≥2% and greater than placebo) include paresthesias, nausea, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms 1
- Naratriptan exerts only minor effects on myocardial blood flow and coronary vasodilator reserve in patients without coronary artery disease 3
- Chest symptoms can occur with triptans, but postmarketing data indicate that true ischemic events are rare 4
Contraindications
Naratriptan is absolutely contraindicated in patients with: 1
- History of coronary artery disease or coronary artery vasospasm
- Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
- History of stroke, transient ischemic attack, hemiplegic or basilar migraine
- Peripheral vascular disease or ischemic bowel disease
- Uncontrolled hypertension
- Recent use (within 24 hours) of another 5-HT1 agonist or ergotamine-containing medication
- Hypersensitivity to naratriptan (angioedema and anaphylaxis have been reported)
- Severe renal or hepatic impairment
Clinical Positioning
- Naratriptan is recommended as a first-line triptan option for moderate to severe migraine attacks, with good evidence supporting its effectiveness 4, 7
- It is particularly useful for patients who experience frequent headache recurrence with other triptans due to its longer half-life 4
- Limit use to no more than 2 days per week to prevent medication-overuse headache 7
- If one triptan fails, trying naratriptan (or another triptan) is reasonable, as failure of one triptan does not predict failure of others 8, 7