What is the recommended as‑needed (prn) dose of zolmitriptan for an adult with episodic migraine?

Zolmitriptan PRN Dose for Migraine

For acute episodic migraine in adults, start with zolmitriptan 2.5 mg orally at headache onset; if inadequate response after 2 hours, a second dose of 2.5 mg may be taken, with a maximum of 10 mg in 24 hours. 1

Dosing Algorithm by Route

Oral Tablet (First-Line)

• Initial dose: 2.5 mg at migraine onset when pain is still mild 1, 2
• Alternative initial dose: 1.25 mg for patients requiring lower exposure (e.g., hepatic impairment) 1
• Maximum single dose: 5 mg 1
• Repeat dosing: May repeat after 2 hours if headache persists or recurs; do not exceed 10 mg per 24 hours 1, 3
• Clinical efficacy: The 2.5 mg dose achieves 62% headache response at 2 hours and 70% at 4 hours, compared to 36% and 37% with placebo, respectively 2

Intranasal Spray (Faster Onset)

• Recommended dose: 5 mg (one spray in one nostril) for optimal efficacy and speed 4
• Alternative dose: 2.5 mg if lower exposure needed 4
• Repeat dosing: May repeat after 2 hours; maximum 10 mg per 24 hours 1
• Speed advantage: The 5 mg nasal spray demonstrates significant headache response versus placebo starting at 15 minutes (versus 30 minutes for oral tablet), with 70.3% achieving 2-hour headache response 4
• Pain-free outcomes: The 5 mg nasal spray produces pain-free rates significantly superior to both placebo and 2.5 mg oral tablet as early as 30 minutes 4

Route Selection Strategy

• Choose oral tablet for typical migraine attacks without severe nausea or vomiting 5, 1
• Choose intranasal spray when rapid onset is critical, when nausea/vomiting limits oral intake, or when early treatment during mild pain phase is desired 5, 4
• Orally disintegrating tablet (ODT) offers convenience without water and can be taken discreetly; 94% of patients achieve reduced headache intensity within 2 hours, with 35% improving within 30 minutes 6, 7

Dose Optimization for Persistent Headache

• If headache persists at mild intensity 2 hours after initial 2.5 mg dose, a second dose of 5 mg (rather than 2.5 mg) provides superior pain-free response (36.0% versus 25.5% with placebo) 3
• If headache persists at moderate or severe intensity 2 hours after initial dose, either 2.5 mg or 5 mg may be used, though efficacy is similar 3
• Approximately 70% of attacks treated with initial 2.5 mg require no further dose; 66% of all attacks are controlled with a single dose 3

Critical Frequency Limitation

• Restrict zolmitriptan use to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 5, 8
• If acute treatment is needed more than twice weekly, initiate preventive therapy immediately 5

Absolute Contraindications

• Coronary artery disease, previous myocardial infarction, or Prinzmetal angina 1
• History of stroke, transient ischemic attack, hemiplegic or basilar migraine 1
• Peripheral vascular disease or ischemic bowel disease 1
• Uncontrolled hypertension 1
• Use of another triptan or ergotamine-containing medication within 24 hours 1
• MAO-A inhibitor use within past 2 weeks 1
• Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders 1

Managing Treatment Failure

• Try zolmitriptan for 2–3 separate migraine attacks before concluding it is ineffective, as response can vary between attacks 9, 8
• If inadequate response after adequate trial, switch to a different triptan (sumatriptan, rizatriptan, eletriptan, naratriptan, almotriptan, or frovatriptan), as failure of one triptan does not predict failure of others 5, 9
• Add an NSAID (naproxen 500 mg or ibuprofen 400–800 mg) to zolmitriptan for synergistic effect if monotherapy provides insufficient relief 5, 9

Special Populations

• Moderate or severe hepatic impairment: Use 1.25 mg dose 1
• Pregnancy: Based on animal data, zolmitriptan may cause fetal harm; use only if potential benefit justifies potential risk 1

Common Adverse Effects

• Unusual taste (most common with nasal spray), paresthesia, neck/throat/jaw pain/tightness/pressure, dizziness, somnolence, warm/cold sensation, nausea, and dry mouth 1, 4
• Adverse events are typically mild to moderate in intensity and short-lived 4, 6
• Chest pressure or heaviness occurs in 3–5% of patients but is generally not associated with myocardial ischemia 8