indication

For the acute treatment of migraine with or without aura in adults.

pharmacology

Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist. In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat.

mechanism of action

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors, and little or no affinity for 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors. Eletriptan has no significant affinity or pharmacological activity at adrenergic alpha1, alpha2, or beta; dopaminergic D1 or D2; muscarinic; or opioid receptors. Two theories have been proposed to explain the efficacy of 5-HT receptor agonists in migraine. One theory suggests that activation of 5-HT1 receptors located on intracranial blood vessels, including those on the arteriovenous anastomoses, leads to vasoconstriction, which is correlated with the relief of migraine headache. The other hypothesis suggests that activation of 5-HT1 receptors on sensory nerve endings in the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

toxicity

Based on the pharmacology of the 5-HT1B/1D agonists, hypertension or other more serious cardiovascular symptoms could occur on overdose.

biotransformation

In vitro studies indicate that eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4. The N-demethylated metabolite of eletriptan is the only known active metabolite.

absorption

Well absorbed after oral administration with a mean absolute bioavailability of approximately 50%.

half life

The terminal elimination half-life of eletriptan is approximately 4 hours.

drug interactions

Citalopram: Increased risk of CNS adverse effects

Clarithromycin: The macrolide, clarithromycin, may increase the effect and toxicity of eletriptan.

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dihydroergotamine: Possible severe and prolonged vasoconstriction

Dihydroergotoxine: Possible severe and prolonged vasoconstriction

Ergonovine: Possible severe and prolonged vasoconstriction

Ergotamine: Possible severe and prolonged vasoconstriction

Erythromycin: The macrolide, erythromycin, may increase the effect and toxicity of eletriptan.

Escitalopram: Increased risk of CNS adverse effects

Fluoxetine: Increased risk of CNS adverse effects

Fluvoxamine: Increased risk of CNS adverse effects

Itraconazole: This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan

Ketoconazole: This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan

Methylergonovine: Possible severe and prolonged vasoconstriction

Methysergide: Possible severe and prolonged vasoconstriction

Nefazodone: Increased risk of CNS adverse effects

Nelfinavir: The protease inhibitor, nelfinavir, may increase the effect and toxicity of eletriptan.

Paroxetine: Increased risk of CNS adverse effects

Ritonavir: The protease inhibitor, ritonavir, may increase the effect and toxicity of eletriptan.

Sertraline: Increased risk of CNS adverse effects

Telithromycin: Telithromycin may reduce clearance of Eletriptan. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Eletriptan if Telithromycin is initiated, discontinued or dose changed.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Troleandomycin: The macrolide, troleandomycin, may increase the effect and toxicity of eletriptan.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of eletriptan by decreasing its metabolism. Consider avoiding administration of the two agents within 72 hours of each other. Monitor for changes in the therapeutic and adverse effects of eletriptan if voriconazole is initiated, discontinued or dose changed.

Zolmitriptan: Concomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and eletriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.