Drug Monograph
Eletriptan (Relpax)
eletriptan hydrobromide
Pharmacokinetic Profile
Half-Life
~4 h (adults); 5.7 h (elderly)
Metabolism
CYP3A4 (primary)
Protein Binding
~85%
Bioavailability
~50%
Volume of Distribution
138 L (IV)
Clinical Information
Drug Class
Triptan (5-HT1B/1D agonist)
Available Doses
20 mg, 40 mg tablets
Route
Oral
Renal Adjustment
None required
Hepatic Adjustment
Avoid in severe impairment
Pregnancy
Use only if benefit outweighs risk
Lactation
Excreted in breast milk; avoid nursing 24 h post-dose
Schedule / Legal Status
Prescription only (not scheduled)
Generic Available
Yes
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Acute migraine with aura | Adults (≥18 years) | Acute abortive therapy | FDA Approved |
| Acute migraine without aura | Adults (≥18 years) | Acute abortive therapy | FDA Approved |
Eletriptan is approved exclusively for acute (abortive) treatment of migraine attacks once the headache phase has begun. It is not indicated for migraine prevention, cluster headache, or hemiplegic/basilar migraine subtypes. A confirmed diagnosis of migraine should be established prior to use. In pivotal trials, the 40 mg dose provided a 2-hour headache response rate of approximately 54–65%, which was superior to placebo across seven adult studies (FDA PI).
Off-Label Uses
Menstrual migraine (short-term prevention): Some clinicians use eletriptan perimenstrually for 5–7 days in women with predictable menstrual-related migraine. Evidence quality: Low (small open-label studies).
Adolescent migraine (age 11–17): A randomized controlled trial of eletriptan 40 mg in adolescents did not demonstrate superiority over placebo (57% response in both groups); therefore, use in this population remains off-label and unsupported. Evidence quality: Low.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Mild-to-moderate migraine, triptan-naive | 20 mg | 20 mg PRN | 80 mg/day | Consider starting low in patients concerned about tolerability May repeat after ≥2 h (max single dose 40 mg) |
| Moderate-to-severe migraine, standard treatment | 40 mg | 40 mg PRN | 80 mg/day | 40 mg achieves higher 2-hour response vs 20 mg May repeat 40 mg after ≥2 h if headache persists or recurs |
| Migraine recurrence after initial response | 40 mg | 40 mg (2nd dose) | 80 mg/day | Second dose at least 2 hours after the first No increase in adverse event frequency with 2 doses in 24 h |
| Patient switching from another triptan due to poor response | 40 mg | 40 mg PRN | 80 mg/day | Use higher dose to maximise efficacy Allow 24 h washout from prior triptan |
| Mild-to-moderate hepatic impairment | 20 mg | 20–40 mg PRN | 80 mg/day | AUC increased ~34%, Cmax ~18%; no formal dose adjustment required Severe hepatic impairment: NOT recommended |
| Elderly patients (≥65 years) | 20 mg | 20–40 mg PRN | 80 mg/day | Half-life prolonged to ~5.7 h; greater BP elevation observed Monitor blood pressure; limited data (n=50 in trials) |
Clinical Pearl: Dosing strategy
The maximum single dose is 40 mg, and the maximum daily dose is 80 mg (two doses). The safety of treating more than an average of 3 migraine attacks in a 30-day period has not been established. Eletriptan can be taken regardless of food intake, though a high-fat meal may increase absorption by 20–30% without clinical significance (FDA PI).
Pharmacology
Mechanism of Action
Eletriptan is a second-generation triptan that selectively activates serotonin 5-HT1B and 5-HT1D receptors, with additional affinity for 5-HT1F receptors. Its antimigraine effect results from two complementary actions: constriction of dilated intracranial blood vessels (via 5-HT1B receptors on vascular smooth muscle) and inhibition of pro-inflammatory neuropeptide release from trigeminal nerve terminals (via 5-HT1D receptors). By suppressing the release of calcitonin gene-related peptide (CGRP), substance P, and vasoactive intestinal peptide, eletriptan interrupts the neurogenic inflammation that drives migraine pain. Compared to first-generation triptans, eletriptan has greater lipophilicity and higher central nervous system penetration, which may contribute to its consistent efficacy in clinical trials.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Oral bioavailability ~50%; Tmax ~1.5 h (healthy), ~2 h (during migraine); AUC/Cmax ↑20–30% with high-fat meal | Rapid onset; can be taken with or without food. Tmax is slightly delayed during active migraine attacks. |
| Distribution | Vd 138 L (IV); protein binding ~85%; high lipophilicity | Large volume of distribution reflects good tissue penetration including CNS. Higher lipophilicity than sumatriptan. |
| Metabolism | CYP3A4 (primary); active N-demethylated metabolite (10–20% of parent; t½ ~13 h) | Contraindicated with potent CYP3A4 inhibitors (ketoconazole increases AUC 6-fold). Active metabolite contributes minimally to clinical effect. |
| Elimination | t½ ~4 h (young adults), ~5.7 h (elderly); renal clearance 3.9 L/h; ~90% non-renal clearance | Predominantly hepatic elimination. No renal dose adjustment needed. Avoid in severe hepatic impairment (not studied). |
Side Effects
≥5%
Very Common (at 40 mg dose vs placebo)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Asthenia (weakness/fatigue) | 5% (vs 3% placebo) | Dose-related; more pronounced at 80 mg (10%). Usually transient and resolves within hours of dosing. |
| Dizziness | 6% (vs 3% placebo) | Dose-related; caution with driving or operating machinery after dosing. |
| Somnolence | 6% (vs 4% placebo) | Dose-related; advise patients to avoid hazardous activities if drowsy. |
| Nausea | 5% (vs 5% placebo) | Similar to placebo at 40 mg. Rises to 8% at 80 mg dose. Often difficult to distinguish from migraine-associated nausea. |
2–4%
Common (at 40 mg dose vs placebo)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Paresthesia | 3% (vs 2% placebo) | Typical triptan sensation; usually transient tingling in extremities or face. |
| Dry mouth | 3% (vs 2% placebo) | Self-limiting; encourage oral hydration. |
| Chest tightness/pain/pressure | 2% (vs 1% placebo) | Usually non-cardiac in origin. However, if high cardiovascular risk, perform cardiac evaluation. |
| Abdominal discomfort | 2% (vs 1% placebo) | Mild epigastric discomfort; rarely requires intervention. |
| Dyspepsia | 2% (vs 1% placebo) | Transient; may be mitigated by taking with food. |
| Dysphagia / throat tightness | 2% (vs 0.2% placebo) | Characteristic triptan-class effect. Distinguish from true allergic angioedema by onset pattern and resolution. |
| Flushing / warmth | 2% (vs 2% placebo) | Self-limited vasomotor symptom; not clinically significant at 40 mg. |
Serious
Serious Adverse Effects (regardless of frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Myocardial ischemia / infarction | Very rare | Within hours of dosing | Discontinue permanently; emergency cardiac evaluation; contraindicated for re-challenge |
| Coronary artery vasospasm (Prinzmetal’s angina) | Very rare | Within hours of dosing | Discontinue permanently; ECG and cardiac monitoring; avoid all triptans in future |
| Stroke / cerebrovascular events | Very rare | Within hours of dosing | Emergency neurological assessment; permanent discontinuation |
| Life-threatening arrhythmias (VT/VF) | Very rare | Within hours of dosing | Immediate resuscitation; permanent discontinuation; cardiology referral |
| Serotonin syndrome | Rare | Minutes to hours (typically with concurrent serotonergic agents) | Discontinue all serotonergic drugs immediately; supportive care; cyproheptadine may be considered |
| Anaphylaxis / angioedema | Very rare | Any time after dosing | Emergency treatment with epinephrine; permanent discontinuation; contraindicated for re-challenge |
| Peripheral vascular ischemia (Raynaud’s) | Very rare | Within hours | Discontinue; evaluate for vasospastic conditions before any further triptan use |
| GI ischemia / colonic infarction | Very rare | Hours to days | Discontinue; urgent surgical/GI evaluation if bloody diarrhea or severe abdominal pain |
| Seizure | Very rare (post-marketing) | Variable | Discontinue; neurological assessment; seizure management as indicated |
Discontinuation
Discontinuation Rates
Long-Term Open-Label Studies (Adults)
8.3% (128 of 1,544 patients over up to 1 year)
Top reasons: Asthenia, nausea, dizziness, somnolence, chest-related symptoms
Controlled Trials (Adults)
Low overall (no increase with repeat dosing)
Key observation: Adverse event frequency did not increase when two doses were taken within 24 hours
Managing Chest-Related Symptoms
Sensations of tightness, pressure, or heaviness in the chest, throat, neck, and jaw are common class-related effects of triptans and are typically non-cardiac in origin. However, patients with multiple cardiovascular risk factors (hypertension, diabetes, hyperlipidaemia, smoking, family history of coronary disease, post-menopausal women, men over 40) warrant a cardiovascular evaluation before first use and, in some cases, the initial dose should be administered in a medically supervised setting with ECG monitoring (FDA PI).
Drug Interactions
Eletriptan is primarily metabolized by CYP3A4, making it highly susceptible to interactions with CYP3A4 inhibitors. It also carries class-wide triptan serotonergic and vasospastic interaction risks. The drug itself has negligible inhibitory potential on other CYP enzymes at therapeutic concentrations.
Major
Potent CYP3A4 Inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, nelfinavir, nefazodone, troleandomycin)
MechanismStrong CYP3A4 inhibition reduces eletriptan metabolism
EffectKetoconazole increases Cmax 3-fold and AUC 6-fold; other potent inhibitors have comparable effects
ManagementContraindicated. Must not use eletriptan within 72 hours of these agents
FDA PI
Major
Ergotamine / Dihydroergotamine (DHE)
MechanismAdditive vasospastic effects through combined 5-HT1B agonism
EffectRisk of prolonged coronary and peripheral vasospasm
ManagementContraindicated within 24 hours of each other
FDA PI
Major
Other Triptans (sumatriptan, rizatriptan, etc.)
MechanismAdditive serotonergic agonism at 5-HT1B/1D receptors
EffectPotential for excessive vasoconstriction and serotonin syndrome
ManagementContraindicated within 24 hours of another triptan
FDA PI
Major
SSRIs / SNRIs / TCAs / MAOIs
MechanismCombined serotonergic activity increases serotonin syndrome risk
EffectCases of serotonin syndrome reported during co-administration
ManagementUse with caution if clinically warranted. Educate patients on serotonin syndrome symptoms. MAOIs pose the highest risk
FDA PI
Moderate
Erythromycin
MechanismModerate CYP3A4 inhibition increases eletriptan exposure
EffectCmax increased ~2-fold, AUC increased ~4-fold
ManagementAvoid concomitant use. If essential, consider azithromycin (minimal CYP3A4 effect) as an alternative macrolide
FDA PI · Clinical PK Study
Moderate
Verapamil
MechanismModerate CYP3A4 inhibition
EffectCmax increased ~2-fold, AUC increased ~3-fold
ManagementAvoid concomitant use or consider alternative migraine treatment when patient takes verapamil chronically
FDA PI · Clinical PK Study
Moderate
Fluconazole
MechanismModerate CYP3A4 inhibition
EffectCmax increased ~1.4-fold, AUC increased ~2-fold
ManagementUse with caution. Consider lower eletriptan dose (20 mg) during concurrent fluconazole therapy
FDA PI · Clinical PK Study
Minor
Propranolol
MechanismUncertain; modest pharmacokinetic interaction
EffectCmax increased ~10%, AUC increased ~33%; no interactive blood pressure rise observed
ManagementNo dose adjustment required. Common combination in migraine patients using propranolol prophylactically
FDA PIMonitoring
-
Cardiovascular Status
Before first dose in at-risk patients
Routine Perform cardiovascular evaluation including ECG in triptan-naive patients with multiple CV risk factors. Consider supervised first dose with ECG in these patients. Periodic evaluation recommended for intermittent long-term users with risk factors. -
Blood Pressure
Each visit
Routine Significant hypertensive episodes have been reported rarely with 5-HT1 agonists. Greater BP elevation observed in elderly patients and those with renal impairment. Contraindicated in uncontrolled hypertension. -
Headache Diary
Ongoing
Routine Track frequency of migraine attacks and eletriptan use. Use of acute migraine drugs ≥10 days/month raises concern for medication overuse headache. Safety of treating >3 attacks per 30-day period not established. -
Hepatic Function
Baseline (if clinically indicated)
Trigger-based Mild-to-moderate hepatic impairment increases AUC by ~34%. Severe hepatic impairment has not been studied; eletriptan is not recommended in this population. -
Serotonin Syndrome Signs
Each use (especially with concurrent serotonergic drugs)
Trigger-based Watch for agitation, hallucinations, tachycardia, labile blood pressure, hyperthermia, hyperreflexia, incoordination, nausea, vomiting, or diarrhoea. Onset typically within minutes to hours of dosing with concurrent serotonergic agents. -
Chest / Cardiac Symptoms
Each use
Trigger-based New chest pain, tightness, or pressure requires evaluation. Most cases are non-cardiac triptan sensations, but coronary ischemia must be excluded in patients with CV risk factors before further use.
Contraindications & Cautions
Absolute Contraindications
- Ischaemic coronary artery disease (angina pectoris, documented silent ischaemia, prior MI) or coronary artery vasospasm including Prinzmetal’s angina
- Wolff-Parkinson-White syndrome or arrhythmias involving cardiac accessory conduction pathways
- History of stroke or transient ischaemic attack (TIA)
- Hemiplegic or basilar migraine (current or past)
- Peripheral vascular disease
- Ischaemic bowel disease
- Uncontrolled hypertension
- Hypersensitivity to eletriptan or any excipient (angioedema/anaphylaxis reported)
- Use within 24 hours of another 5-HT1 agonist or ergotamine-containing medication
- Use within 72 hours of potent CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir)
Relative Contraindications (Specialist Input Recommended)
- Multiple cardiovascular risk factors (hypertension, hyperlipidaemia, smoking, diabetes, obesity, strong family history of CAD, post-menopausal women, men >40) — requires cardiovascular evaluation with negative findings before first dose; consider supervised first administration
- Concurrent use of moderate CYP3A4 inhibitors (erythromycin, verapamil, fluconazole) — significant increases in eletriptan exposure; risk-benefit discussion needed
- Concurrent serotonergic therapy (SSRIs, SNRIs, TCAs) — serotonin syndrome risk exists; if warranted, educate patient on warning symptoms
Use with Caution
- Mild-to-moderate hepatic impairment — AUC increased ~34%; monitor for enhanced effect
- Elderly patients (≥65 years) — half-life prolonged to ~5.7 h; greater blood pressure elevations observed; limited trial data
- Renal impairment — no dose adjustment needed, but blood pressure elevations observed in this population
- Seizure history — seizure reported in post-marketing surveillance
FDA Class-Wide Regulatory Warning
Cardiovascular Risk with 5-HT1 Agonists (Triptans)
Serious and potentially fatal cardiac adverse reactions, including acute myocardial infarction, have occurred within hours of triptan administration. Some events have been reported in patients without known coronary artery disease. Cerebrovascular events including stroke, haemorrhage, and transient ischaemic attack have also been reported. In some cases, the cerebrovascular event was primary and the triptan was administered under the mistaken belief that symptoms were migraine-related. Prescribers should perform a cardiovascular evaluation in patients with multiple risk factors prior to prescribing any triptan (FDA PI).
Patient Counselling
Purpose of Therapy
Eletriptan is a rescue medication taken at the onset of a migraine headache to reduce pain and associated symptoms. It works best when taken early in the migraine attack. It does not prevent future migraines and must not be used as a daily preventive therapy. Taking this or similar acute medications more than 10 days per month can paradoxically worsen headaches (medication overuse headache).
How to Take
Swallow the tablet whole with water. The usual starting dose is 40 mg taken as a single tablet at the onset of migraine. If the headache does not resolve or returns, a second tablet may be taken at least 2 hours after the first, but the total dose should not exceed 80 mg in any 24-hour period. Eletriptan can be taken with or without food.
Chest, Throat, or Jaw Tightness
Tell patient
A sensation of tightness or pressure in the chest, throat, or jaw is a common triptan effect and is usually not heart-related. It typically resolves within 30 minutes. This does not mean the medication is dangerous, but any new or unusual chest symptoms should be reported.
Call prescriber
If chest pain is severe, sudden, or accompanied by shortness of breath, arm pain, sweating, or fainting, seek emergency medical care immediately.
Drowsiness and Dizziness
Tell patient
Dizziness and drowsiness occur in approximately 6% of patients at the 40 mg dose. Avoid driving, operating machinery, or other hazardous activities until you know how the medication affects you.
Call prescriber
If dizziness is severe, does not resolve, or is accompanied by confusion, slurred speech, or visual changes, contact your doctor promptly as these may suggest a more serious condition.
Medication Overuse Headache
Tell patient
Using any acute migraine medication (including eletriptan) on 10 or more days per month can lead to more frequent headaches. Keep a headache diary to track your migraine frequency and medication use.
Call prescriber
If you notice your headaches becoming more frequent or you are needing to use eletriptan more often, contact your prescriber to discuss preventive strategies.
Serotonin Syndrome Risk (if taking antidepressants)
Tell patient
If you are taking an SSRI (e.g., sertraline, fluoxetine), SNRI (e.g., venlafaxine, duloxetine), or other serotonergic medications, there is a small risk of a condition called serotonin syndrome when combined with eletriptan. Symptoms include agitation, confusion, rapid heartbeat, high body temperature, muscle twitching, and diarrhoea.
Call prescriber
Seek immediate medical attention if you experience any combination of these symptoms after taking eletriptan.
Drug Interactions with CYP3A4 Inhibitors
Tell patient
Certain antibiotics (clarithromycin, erythromycin), antifungals (ketoconazole, itraconazole), and HIV medications (ritonavir, nelfinavir) dramatically increase eletriptan blood levels. Always inform any prescriber that you use eletriptan for migraines.
Call prescriber
Before starting any new prescription medication, verify it does not interact with eletriptan. Do not take eletriptan within 72 hours of a potent CYP3A4 inhibitor.
Pregnancy and Breastfeeding
Tell patient
Animal studies suggest potential fetal harm. If you are pregnant or planning pregnancy, discuss migraine management options with your prescriber. Eletriptan passes into breast milk; if nursing, avoid breastfeeding for 24 hours after taking a dose.
Call prescriber
Notify your doctor immediately if you become pregnant while using eletriptan.
Sources
Regulatory (PI / SmPC)
- Relpax (eletriptan hydrobromide) tablets, for oral use. Full Prescribing Information. Viatris Specialty LLC. Revised January 2024. DailyMed Primary regulatory reference for all dosing, contraindications, adverse effect incidence data, pharmacokinetics, and drug interaction data in this monograph.
- Relpax (eletriptan hydrobromide) tablets. Original NDA 021016 label. Roerig/Pfizer Inc. Revised March 2020. Pfizer Labeling Earlier version of the Pfizer label used to cross-reference adverse event data and clinical study results.
Key Clinical Trials
- Goadsby PJ, Ferrari MD, Olesen J, et al. Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan. Neurology. 2000;54(1):156–163. doi:10.1212/WNL.54.1.156 Head-to-head trial demonstrating eletriptan 80 mg superiority over sumatriptan 100 mg at 2-hour response; supports dosing efficacy data.
- Mathew NT. Tolerability and safety of eletriptan in the treatment of migraine: a comprehensive review. Headache. 2003;43(9):962–974. doi:10.1046/j.1526-4610.2003.03188.x Comprehensive safety review across >11,000 subjects and 74,000 treated attacks, confirming favourable tolerability at 40 mg.
- Diener HC, Ryan R, Sun W, Hettiarachchi J. The 40-mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg. Cephalalgia. 2004;24(11):947–954. doi:10.1111/j.1468-2982.2004.00782.x Pooled analysis supporting eletriptan 40 mg as the standard effective dose with a favourable tolerability profile.
Guidelines
- American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1–18. doi:10.1111/head.13456 AHS consensus recommendations on acute migraine treatment positioning triptans as first-line therapy.
- Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Neurology. 2012;78(17):1337–1345. doi:10.1212/WNL.0b013e3182535d20 AAN guideline providing context on when to escalate from acute therapy to preventive treatment.
Mechanistic / Basic Science
- Napier C, Stewart M, Melrose H, et al. Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]-eletriptan binding at human 5-HT1B and 5-HT1D receptors. Eur J Pharmacol. 1999;368(2–3):259–268. doi:10.1016/S0014-2999(99)00026-6 Receptor binding study establishing eletriptan’s high affinity and selectivity for 5-HT1B/1D receptors, underpinning the mechanism of action section.
- Tepper SJ, Rapoport AM, Sheftell FD. Mechanisms of action of the 5-HT1B/1D receptor agonists. Arch Neurol. 2002;59(7):1084–1088. doi:10.1001/archneur.59.7.1084 Review of triptan class mechanism covering trigeminal inhibition and cranial vasoconstriction pathways.
Pharmacokinetics / Special Populations
- Milton KA, Scott NR, Allen MJ, et al. Pharmacokinetics, pharmacodynamics, and safety of the 5-HT1B/1D agonist eletriptan following intravenous and oral administration. J Clin Pharmacol. 2002;42(5):528–539. doi:10.1177/00912700222011580 Foundational PK study establishing eletriptan’s bioavailability (~50%), half-life (~4 h), and dose-proportional pharmacokinetics.
- Kim YK, Shin KH, Alderman J, et al. Pharmacokinetics and tolerability of eletriptan hydrobromide in healthy Korean subjects. Drug Des Devel Ther. 2018;12:331–337. doi:10.2147/DDDT.S145593 Cross-ethnic PK comparison confirming similar bioavailability and tolerability between Korean and non-Korean subjects.
- Takiya L, Piccininni LC, Kamath V. Safety and efficacy of eletriptan in the treatment of acute migraine. Pharmacotherapy. 2006;26(1):115–128. doi:10.1592/phco.2006.26.1.115 Comprehensive review of eletriptan clinical trial data including safety, tolerability, and efficacy across multiple studies.