What are the recommended sumatriptan dosing regimens for acute migraine in adults and adolescents, including oral, intranasal, and subcutaneous routes, repeat‑dose limits, combination with naproxen, and contraindications?

Sumatriptan Dosing Recommendations for Acute Migraine

For adults with acute migraine, sumatriptan should be administered as 50–100 mg orally, 6 mg subcutaneously, or 5–20 mg intranasally at the onset of headache, with combination therapy (sumatriptan + naproxen 500 mg) providing superior efficacy to either agent alone. 1, 2, 3

Route-Specific Dosing and Administration

Oral Sumatriptan

• Initial dose: 50–100 mg at migraine onset; the 100 mg dose provides better pain-free response at 2 hours (NNT 5.1) compared to 25 mg (NNT 7.5), while 50 mg shows similar headache relief (NNT 3.2) 4, 5
• Repeat dosing: May repeat after 2 hours if headache returns or partial response occurs 3
• Maximum daily dose: 200 mg per 24 hours 2, 3
• Efficacy: 50 mg and 100 mg doses provide greater effect than 25 mg, but 100 mg does not provide substantially greater benefit than 50 mg 3

Subcutaneous Sumatriptan

• Initial dose: 6 mg at migraine onset 2, 6
• Repeat dosing: May repeat once after 1 hour if needed 2
• Maximum daily dose: 12 mg per 24 hours 2, 6
• Efficacy: Provides the highest efficacy among all routes, with 59–82% response rate and onset within 15 minutes 1, 2

Intranasal Sumatriptan

• Initial dose: 5–20 mg at migraine onset 1, 2
• Repeat dosing: May repeat after 2 hours 2
• Maximum daily dose: 40 mg per 24 hours 2
• Indication: Particularly useful when significant nausea or vomiting is present 1

Combination Therapy with Naproxen

Sumatriptan plus naproxen sodium is superior to either agent alone and represents the strongest evidence-based recommendation for moderate-to-severe migraine. 1, 7

• Dosing: Sumatriptan 85 mg (or 50 mg) + naproxen sodium 500 mg at migraine onset 7, 8
• Efficacy advantage: Provides 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared to sumatriptan alone 1
• NNT for pain-free at 2 hours: 3.1 when baseline pain is mild; 4.9 when baseline pain is moderate or severe 7
• Early treatment benefit: Treating when pain is still mild yields 50% pain-free response versus 28% when treating moderate-to-severe pain 1, 7

Repeat-Dose Limits and Medication-Overuse Prevention

All acute migraine medications, including sumatriptan, must be limited to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache. 1, 2

• Triptans trigger medication-overuse headache at ≥10 days per month, a lower threshold than NSAIDs (≥15 days per month) 1
• If acute treatment is required more than twice weekly, preventive therapy must be initiated immediately 1
• Medication-overuse headache paradoxically increases headache frequency and can lead to daily headaches 1, 2

Adolescent Dosing (Ages 12–17)

• Intranasal sumatriptan 5–10 mg is the only FDA-approved triptan formulation for adolescents 9, 6
• First-line treatment: NSAIDs (ibuprofen 400–800 mg or naproxen 500 mg) are preferred over triptans due to lack of proven efficacy and documented serious adverse events in this age group 9
• Pediatric safety concern: Serious adverse events including stroke, visual loss, myocardial infarction, and death have been reported in postmarketing surveillance 6
• Not recommended: Oral and subcutaneous sumatriptan are not recommended for patients under 18 years 6

Absolute Contraindications

Sumatriptan is contraindicated in the following conditions: 2, 6

• Ischemic heart disease, previous myocardial infarction, or coronary artery vasospasm (Prinzmetal angina)
• Uncontrolled hypertension
• Cerebrovascular disease, history of stroke or TIA
• Hemiplegic or basilar migraine
• Concurrent use of MAO-A inhibitors (causes unpredictable elevations in bioavailability) 3
• Within 24 hours of ergotamine, dihydroergotamine (DHE), or another triptan 2

Managing Inadequate Response

If sumatriptan fails after 2–3 headache episodes, switch to a different triptan rather than increasing dose or frequency, because failure of one triptan does not predict failure of others. 1, 2

• Alternative triptans include rizatriptan 10 mg (fastest oral triptan, peak 60–90 min), eletriptan 40 mg, zolmitriptan 2.5–5 mg, or naratriptan (longest half-life, may decrease recurrence) 1
• If all triptans fail after adequate trials, escalate to CGRP antagonists (ubrogepant, rimegepant) 1
• Do not increase sumatriptan dose or frequency—instead add an NSAID or switch to combination therapy 2

Special Populations

Hepatic Impairment

• Maximum single oral dose should not exceed 50 mg due to unpredictable elevations in bioavailability 3

Pregnancy and Lactation

• Pregnancy Category C: Use only if potential benefit justifies potential risk; sumatriptan caused embryolethality in rabbits at doses equivalent to human exposure 6
• Lactation: Sumatriptan is excreted in breast milk; avoid breastfeeding for 12 hours after subcutaneous administration 6

Elderly Patients

• Not recommended: Elderly patients have higher risk of coronary artery disease, decreased hepatic function, and more pronounced blood pressure elevations 6

Common Adverse Effects

• Cardiovascular sensations: Chest pressure, heaviness, or warmth occur in 3–5% of patients 2
• Most common in adults: Dizziness, pain or pressure sensations, nausea, somnolence, dry mouth, dyspepsia, paraesthesia 8
• Most common in adolescents: Nasopharyngitis, hot flushes, muscle tightness 8
• Frequency: Adverse events more common with 100 mg (NNH 7.1) than placebo; 50 mg and 25 mg did not show statistically significant difference 4, 5

Critical Prescribing Pitfalls to Avoid

• Never use sumatriptan within 24 hours of another triptan or DHE due to additive vasoconstrictive effects 2
• Never prescribe for patients on MAO inhibitors (contraindicated) 2, 3
• Never increase frequency beyond 2 days per week—this creates medication-overuse headache and guarantees treatment failure 1
• Never abandon triptan therapy after a single failed attempt—individual patients respond differently to different triptans 1, 2
• Never delay adding an NSAID if monotherapy is insufficient—combination therapy is superior to dose escalation 1, 2