Eletriptan is a second-generation triptan, approved by FDA for the acute treatment of migraine with or without aura in adults. It is an orally administered drug with higher lipophilicity and longer duration of action, contributing to its higher efficacy and safety in patients experiencing moderate to severe migraine attacks. It should be only indicated after a clear diagnosis of migraine is established. It is not recommended for treatment of cluster headache and the prophylactic therapy of migraine.¹

Pharmacological class: Serotonin (5-HT1B/1D) receptor agonist

• Migraine

Migraine is usually caused due to vasodilation of cranial vessels and/or release of sensory neuropeptides in the trigeminal system. Eletriptan acts by blocking 5-HT1B/1D receptors present on sensory nerves and intracranial blood vessels of trigeminal system, thereby resulting in constriction of cranial vessels and inhibition of release of neuropeptides.¹

• The usual single dose for migraine is 20 mg or 40 mg

• The dose can be repeated after 2 hours if required, but it should not exceed 80 mg in a period of 24-hour

• Absorption: It is rapidly absorbed after oral administration. The peak plasma levels reaches approximately 1.5 hours after dosing in healthy patients. The median Tmax is 2.0 hours in moderate-severe migraine patients. The mean bio-availability is 50% approximately.
• Volume of Distribution (V_d): 138L after intravenous (IV) administration
• Protein Binding: Moderate and approximately 85%
• Metabolism: The N-demethylated metabolite is the only known active metabolite of eletriptan. It is  metabolized by cytochrome P-450 enzyme CYP3A4.
• Route of elimination: The mean renal clearance is approximately 3.9 L/h after oral administration. Non-renal clearance accounts for about 90% of the total clearance
• Half-life: It is rapidly eliminated with a half-life of 4h¹

Eletriptan is contraindicated in patients with:

• History of coronary artery disease (CAD), stroke and transient ischemic attack
• Wolff-Parkinson-White syndrome
• History of hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Hypersensitivity to eletriptan¹

• Ergot-Containing Drugs: Prolonged vasospastic reactions occur by the administration of ergot containing drugs. These effects may increase when ergot or ergotamine containing drugs and eletriptan are used within 24 hours of each other.
• Other 5-HT1B/1D Agonists: Concomitant use of eletriptan with other 5-HT1 agonists is also contraindicated with 24h of administration due to increased risk of cardiovascular adverse events
• CYP3A4 Inhibitors: The use of potent CYP3A4 inhibitors significantly increase eletriptan exposure, therefore, should not be used within at least 72 hours of treatment with potent CYP3A4 inhibitors
• Selective Serotonin Reuptake Inhibitors (SSRI) /Serotonin Norepinephrine Reuptake Inhibitors (SNRI): The concomitant administration of triptans with SSRIs, SNRIs, TCAs and MAO inhibitors increases the risk of serotonin syndrome¹

The major adverse events associated with the use of eletriptan are asthenia, nausea, dyspepsia, abdominal pain, chest pain, dizziness, paresthesia and somnolence¹

• Eletriptan is not recommended for use in severe hepatic impairment patients
• Monitor blood pressure levels before starting treatment with eletriptan
• Patients with multiple cardiovascular risk factors should be pre-evaluated for cardiac abnormalities before use of eletriptan
• Discontinue eletriptan if arrhythmia, cerebrovascular events, peripheral vasospastic reactions, gastrointestinal ischemia or infarction events occur
• Evaluate high-risk patients for CAD before administration of eletriptan
• Detoxification of medication overuse headache patients necessary, before administering eletriptan in patients
• Eletriptan may cause serotonin syndrome, so discontinue use in suspected cases
• The risk and benefits to both mother and infant should be considered while administering eletriptan in pregnant and breastfeeding mothers¹

Several trials has reported the significant clinical efficacy and tolerability of eletriptan in the treatment of acute migraine. Below is a summary of trials indicating efficacy and safety of eletriptan:

Eletriptan versus placebo

• In a recent study conducted by Almas and Marmura et al., eletriptan at a dose of 40 and 80mg was significantly more effective than placebo in achieving a 2-hour headache response with low adverse events^2,3
• In another trial conducted by Brandes et al., eletriptan 20-40mg showed headache-free rates of 35% and 47% for 20mg and 40mg respectively at 2 hours compared to 22% in placebo group⁴
• In a placebo-controlled study conducted by Sheftell et al., eletriptan showed a 2-hour headache-relief rate of 47% for 20mg, 62% for 40mg and 59% for 80mg dose compared to 22% in placebo group⁵
• Another placebo-controlled trial conducted by Stark et al., eletriptan was found to be superior to placebo for headache relief at 2 hours on all available doses if 20, 40 and 80mg⁶

Eletriptan versus other triptans

• A meta-analysis conducted by Bhambri et al., eletriptan was found to more effective compared to all the marketed triptans⁷
• In another recent meta-analysis of 74 trials, eletriptan 40mg was found to be superior for either pain-free response or sustained headache response at 2 hours, compared to all the other triptans⁸
• In another comparative study conducted by Garcia-Ramos et al., eletriptan 40mg showed a superior clinical efficacy than naratriptan 2.5 mg, but the adverse event profile was similar for both drugs. It also increases the 2 hours pain and sustained headache-free response and reduced the need of rescue medications⁹
• In a double-blind, double-dummy, parallel-group study conducted by Mathew et al., eletriptan 40 mg was found to be superior to sumatriptan 100mg in treating migraine pain, associated symptoms and restoring patient function¹⁰
• In a triptan-switch study conducted by Bhambri et al., eletriptan 40mg was found to be effective and safe in patients who did not respond to treatment with rizatriptan and NSAIDs⁷

1. Eletriptan. FDA LABEL. Reference ID: 3383349
2. Headache. 2015 Jan;55(1):3-20.
3. Cephalalgia. 2014 Feb;34(2):126-35.
4. Cephalalgia. 2005 Sep;25(9):735-42. d
5. Headache. 2003 Mar;43(3):202-13.
6. Cephalalgia. 2002 Feb;22(1):23-32.
7. Int J Gen Med. 2015 Jan 12;8:27-36.
8. Cephalalgia. 2014 Apr;34(4):258-67.
9. Cephalalgia. 2003 Nov;23(9):869-76.
10. Headache. 2003 Mar;43(3):214-22.