Eletriptan

Drug Reference 5 min 1747

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Created On: 21/01/2021

Eletriptan is a second-generation triptan, approved by FDA for the acute treatment of migraine with or without aura in adults.

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Introduction

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

Indications

Migraine

Pharmachologic action

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

Dosage

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

Pharmacokinetics

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

Contraindications

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

Drug interaction

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

Side effects

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

Precautions

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

Clinical evidence

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