RELPAX

Indications

• Acute migraine attacks

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Initial dose of 12.5 mg to be taken as soon as possible after the onset of a migraine, with a second dose of 12.5 mg allowed after 2 hours if necessary. The maximum daily dose should not exceed 25 mg.

Mechanism of action

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D, and 5-HT1F receptors. Its action on the 5-HT1B receptors located on intracranial blood vessels induces vasoconstriction, which is associated with the relief of migraine headaches. Additionally, activation of 5-HT1D receptors on sensory nerve endings in the trigeminal system inhibits the release of pro-inflammatory neuropeptides, further contributing to its therapeutic effect.

Pharmacodynamics

As a selective 5-HT1 receptor agonist, eletriptan modulates vascular tone by causing vasoconstriction of cranial blood vessels. In animal studies, it has been shown to reduce carotid arterial blood flow with minimal impact on systemic blood pressure. Eletriptan also exhibits an inhibitory effect on trigeminal nerve activity, which plays a crucial role in migraine pathophysiology.

Pharmacokinetics

Eletriptan is absorbed quickly following oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes, and is eliminated through urine. The elimination half-life is approximately 4 hours, allowing for the administration of a second dose if necessary, provided it is taken for the same migraine episode.

Contra-indications

• Arrhythmias
• Coronary vasospasm
• Heart failure
• Ischaemic heart disease
• Peripheral vascular disease
• Previous cerebrovascular accident
• Previous myocardial infarction
• Previous transient ischaemic attack
• Prinzmetal’s angina
• Severe hypertension
• Uncontrolled hypertension

Adverse effects

• Nausea
• Pain
• Palpitations
• Throat tightness
• Vertigo
• Agitation
• Decreased appetite
• Arthralgia
• Constipation
• Gastrointestinal disorders
• Hyperbilirubinaemia
• Lymphadenopathy
• Menorrhagia

Interactions

• Cobicistat: Severe (increases exposure)
• Idelalisib: Severe (increases exposure)
• Erythromycin: Severe (increases exposure)
• Cenobamate: Moderate (decreases exposure)

Precautions

• Conditions which predispose to coronary artery disease
• Elderly patients
• Hepatic impairment (caution in mild to moderate impairment; avoid in severe impairment)

Pregnancy

There is limited experience of using 5-HT1 receptor agonists during pregnancy; manufacturers advise that they should be avoided unless the potential benefit outweighs the risk.

Breast-feeding

Present in milk in animal studies; avoid breastfeeding for 24 hours.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets 40 mg
• Tablets 80 mg

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. In contrast, eletriptan displays insignificant pharmacological activity at adrenergic alpha1, alpha2, or beta; dopaminergic D1 or D2; muscarinic; or opioid receptors. While the full mechanism of action of 5-HT receptor agonists in relieving migrains is not fully elucidated, it is proposed that the activation of 5-HT1 receptors located on intracranial blood vessels leads to vasoconstriction that correlates with the relief of migraine headaches. It is also proposed that the activation of 5-HT1 receptors on sensory nerve endings in the trigeminal system leads to the inhibition of release of pro-inflammatory neuropeptides.

Pharmacodynamics

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.