Eletriptan
Eletriptan is a selective serotonin (5-HT1B/1D) receptor agonist medication approved for the acute treatment of migraine headaches with or without aura in adults.[1] Marketed under the brand name Relpax by Pfizer and as generic eletriptan hydrobromide tablets, it is available as oral tablets in 20 mg and 40 mg strengths and does not prevent future migraines or reduce their frequency.[2] Chemically known as 5-[2-(benzenesulfonyl)ethyl]-3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indole with the molecular formula C22H26N2O2S, eletriptan has a bioavailability of approximately 50% and a half-life of about 4 hours.[3] Eletriptan exerts its therapeutic effects by activating 5-HT1B receptors on cerebral blood vessels to induce vasoconstriction and by stimulating 5-HT1D receptors on sensory nerves to inhibit neurogenic inflammation and the release of pro-inflammatory neuropeptides.[1] It is primarily metabolized in the liver via the cytochrome P450 3A4 (CYP3A4) enzyme, producing an active N-demethylated metabolite with similar but less potent serotonin agonist activity.[3] The drug reaches peak plasma concentrations 1.5 to 2 hours after oral administration and is primarily eliminated in the feces and urine, with about 90% via non-renal routes.[1][4] For administration, eletriptan is typically taken as a single 20 mg or 40 mg dose at the onset of a migraine attack, with a possible second dose after at least 2 hours if needed, but not exceeding 80 mg in 24 hours. The safety of treating more than 3 headaches in any 30-day period has not been established.[2][4] It should not be used prophylactically or during the aura phase alone. Common adverse effects include dizziness, nausea, paresthesia, flushing, and sensations of chest tightness or pressure, while serious risks involve serotonin syndrome, myocardial ischemia, or stroke, particularly in patients with cardiovascular risk factors.[1] Contraindications include coronary artery disease, uncontrolled hypertension, hypersensitivity to the drug, and concurrent use with potent CYP3A4 inhibitors (e.g., ketoconazole) within 72 hours; use with other serotonergic agents is cautioned due to risk of serotonin syndrome.[1][4] Monitoring for cardiovascular effects and migraine response is recommended in at-risk individuals.[1]Medical Uses
Indications
Eletriptan is approved for the acute treatment of migraine headaches with or without aura in adults.[5] It is not indicated for prophylactic migraine therapy, the treatment of hemiplegic migraine, or basilar-type migraine.[5] Eletriptan is included on the World Health Organization's Model List of Essential Medicines (24th list, 2025) as an effective and safe abortive agent for acute migraine attacks in adults.[6] A 2024 network meta-analysis of licensed oral drugs for acute migraine management demonstrated eletriptan's superior efficacy over newer agents such as lasmiditan and ubrogepant, with odds ratios for pain freedom at 2 hours ranging from 1.46 to 3.01 compared to other interventions.[7] In pivotal clinical trials, the 40 mg dose of eletriptan achieved headache response rates of 55-77% at 2 hours post-dose, significantly outperforming placebo.[8][9]Dosage and Administration
Eletriptan is available as oral tablets in 20 mg and 40 mg strengths, formulated as orange, round, convex, film-coated tablets for immediate release.[5] The recommended initial dose for the acute treatment of migraine in adults is 20 mg or 40 mg taken orally as soon as symptoms appear, with a maximum single dose of 40 mg.[5] If the migraine persists or recurs, a second dose of 20 mg or 40 mg may be taken at least 2 hours after the initial dose, but the total dose should not exceed 80 mg in any 24-hour period.[5] The safety of treating more than three migraine attacks in any 30-day period has not been established.[5] Tablets should be swallowed whole with water and may be taken with or without food, as food does not significantly affect absorption.[5] No specific administration instructions beyond these are required for standard use. Dose adjustments are not necessary for patients with mild to moderate renal or hepatic impairment, nor for differences in age, gender, or race.[5] However, no dose adjustment is needed even in severe renal impairment, while eletriptan is not recommended for use in severe hepatic impairment due to increased exposure.[5] Caution is advised in elderly patients, as they may experience greater increases in blood pressure.[5] Recent research has explored alternative formulations to potentially accelerate onset of action; a 2023 study developed and evaluated statistically optimized polymeric buccal films of eletriptan hydrobromide, demonstrating promising in vivo pharmacokinetics for faster transmucosal delivery, though this formulation is not yet approved for clinical use.[10]Safety and Tolerability
Contraindications
Eletriptan is contraindicated in patients with ischemic or vasospastic coronary artery disease, including those with a history of myocardial infarction, Prinzmetal's angina, or other forms of coronary vasospasm, due to the risk of serious cardiovascular events from its vasoconstrictive effects.[11] It is also prohibited in individuals with Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders, as these conditions increase the potential for arrhythmias.[11] The drug must not be used in patients with a history of cerebrovascular events, such as stroke or transient ischemic attack, or in those with hemiplegic or basilar migraine, owing to the heightened risk of cerebral vasoconstriction and ischemia.[11] Similarly, eletriptan is contraindicated in the presence of peripheral vascular disease or ischemic bowel disease, where vascular compromise could be exacerbated.[11] Uncontrolled hypertension represents another absolute contraindication, as the medication may further elevate blood pressure.[11] Eletriptan should not be administered within 24 hours of treatment with another 5-HT1B/1D agonist (triptan) or an ergotamine-containing or ergot-type medication, to avoid additive effects on the serotonergic and vascular systems.[11] Concurrent or recent use (within 72 hours) of potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir, is also contraindicated due to significantly increased exposure to eletriptan, potentially leading to excessive vasoconstriction.[11] Hypersensitivity to eletriptan hydrobromide or any component of the formulation is an absolute contraindication, with reports of angioedema and anaphylaxis in such cases.[11]Use in Specific Populations
Pregnancy
Risk Summary: Based on findings from animal reproduction studies, eletriptan may cause fetal harm when administered to a pregnant woman. There are limited data on eletriptan use in pregnant women to inform a drug-associated risk. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.[11]Lactation
Eletriptan is present in human milk. There are no data on the effects of eletriptan on the breastfed infant or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for eletriptan and any potential adverse effects on the breastfed infant from eletriptan or from the underlying maternal condition. The time to maximum plasma concentration (Tmax) after administration of a 40 mg dose of eletriptan is 1.5 hours, and the half-life is approximately 4 hours. Infants exposed to eletriptan through breast milk are expected to have low levels of exposure, but breastfeeding should be avoided for 24 hours after treatment.[11]Pediatrics
Safety and effectiveness of eletriptan have not been established in pediatric patients.[11]Geriatrics
Clinical studies of eletriptan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.[11]Renal Impairment
No dose adjustment is necessary for patients with mild to moderate renal impairment. Experience with eletriptan in patients with severe renal impairment is limited.[11]Hepatic Impairment
No dose adjustment is necessary for patients with mild to moderate hepatic impairment. The use of eletriptan in patients with severe hepatic impairment is not recommended due to limited pharmacokinetic data.[11]Adverse Effects
Eletriptan is generally well-tolerated, with most adverse effects being mild to moderate and transient in nature.[12] Common adverse effects, occurring at incidences of 1% to 10% and greater than placebo, include asthenia (weakness or fatigue), somnolence (drowsiness), dizziness, nausea, paresthesia (tingling sensations), dry mouth, and sensations of chest tightness, pain, or pressure.[12] These effects are often dose-related, with higher incidences observed at the 40 mg and 80 mg doses compared to 20 mg; for example, asthenia occurred in 10% of patients receiving 80 mg versus 5% at 40 mg and 4% at 20 mg.[12] Less common effects (1% to 10%) may include flushing or feelings of warmth, as well as initial worsening of headache in some users.[1] The following table summarizes the incidence of selected adverse reactions from placebo-controlled clinical trials (≥2% and >placebo):[12]| Adverse Reaction | Placebo (n=988) | 20 mg (n=431) | 40 mg (n=1774) | 80 mg (n=1932) |
|---|---|---|---|---|
| Asthenia | 3% | 4% | 5% | 10% |
| Somnolence | 4% | 3% | 6% | 7% |
| Dizziness | 3% | 3% | 6% | 7% |
| Nausea | 5% | 4% | 5% | 8% |
| Paresthesia | 2% | 3% | 3% | 4% |
| Dry mouth | 2% | 2% | 3% | 4% |
| Chest tightness/pain/pressure | 1% | 1% | 2% | 4% |