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Eletriptan

A Review of its Use in the Acute Treatment of Migraine

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Summary

Abstract

Eletriptan (Relpax®) is an orally administered, lipophilic, highly selective serotonin 5-HT1B/1D receptor agonist (‘triptan’) that is effective in the acute treatment of moderate to severe migraine attacks in adults. It has a rapid onset of action and demonstrates superiority over placebo as early as 30 minutes after the administration of a single 40 or 80mg oral dose. The efficacy of eletriptan 20mg was similar to that of sumatriptan 100mg, while eletriptan 40 and 80mg displayed greater efficacy than sumatriptan 50 or 100mg for most endpoints. Eletriptan 40mg was generally superior to naratriptan 2.5mg and equivalent to almotriptan 12.5mg, rizatriptan 10mg and zolmitriptan 2.5mg, while eletriptan 80mg was superior to zolmitriptan 2.5mg for most efficacy parameters. Eletriptan 40 and 80mg were consistently superior to ergotamine/caffeine. Eletriptan is generally well tolerated, reduces time lost from normal activities, improves patients’ health-related quality of life and appears to be at least as, if not more, cost effective than sumatriptan. Eletriptan is therefore a useful addition to the triptan family and a first-line treatment option in the acute management of migraine attacks.

Pharmacological Properties

Eletriptan binds selectively and with high affinity to 5-HT1d, 5-HT1b and 5-HT 1f receptors. The affinities of eletriptan for 5-HT1b and 5-HT1d receptors are 4-and 8-fold higher, respectively, than those of sumatriptan. Eletriptan and sumatriptan have similar affinities for 5-HT1f receptors.

Eletriptan inhibits various indices of neurogenic inflammation in animal models. The drug’s high central serotonergic effects are probably related more to its potency than to its high lipophilicity, since it is a substrate of the P-glycoprotein multidrug efflux pump, which would limit the brain penetration of eletriptan.

Oral eletriptan is rapidly absorbed, with a time to maximum plasma concentration (tmax) of 0.75–1.5 hours in healthy volunteers. However, during a migraine attack, absorption is significantly delayed (tmax increased from 1.3 to 2.8 hours) and the maximum plasma concentration (Cmax) is reduced by 31%. The Cmax and area under the plasma concentration-time curve increased linearly with increasing dose of eletriptan. The volume of distribution was 138–184 L and the half-life was 4.4–6.5 hours. Eletriptan is extensively metabolised by the cytochrome P450 isoenzyme 3A4, with <20% of the dose detected as unchanged drug in total excreta.

Therapeutic Efficacy

Eletriptan 20–80mg produced significantly higher responses than placebo for the common primary endpoint of headache response at 1 or 2 hours post-dose. Eletriptan 80mg, and eletriptan 40mg in two of three studies, were also superior to placebo at 0.5 hours post-dose. The efficacy of eletriptan was consistent across three successive migraine attacks.

Eletriptan 20mg was as effective as sumatriptan 100mg for all measures of efficacy assessed. Eletriptan 40 and 80mg were often superior to sumatriptan 50 or 100mg for headache response at 1 and 2 hours, pain-free response at 2 hours, functional response at 2 hours and sustained pain-free response at 24 hours. Eletriptan was superior to sumatriptan for headache recurrence and use of rescue medication in one of three studies. The efficacy of eletriptan 40mg was generally similar to that of almotriptan 12.5mg, rizatriptan 10mg and zolmitriptan 2.5mg. With respect to headache response at 1 and 2 hours and sustained pain-free response, eletriptan 40mg was superior to naratriptan 2.5mg and eletriptan 80mg was superior to zolmitriptan 2.5mg. Both eletriptan 40 and 80mg were superior to ergotamine/caffeine 2mg/200mg with respect to headache response at 1 and 2 hours.

Tolerability

Eletriptan 80mg (and generally also 40mg) improved the health-related quality of life in migraineurs to a greater extent than ergotamine/caffeine, and to at least the same extent as sumatriptan 50 and 100mg. Eletriptan 40mg was considered to be at least as or more cost effective than sumatriptan 50 or 100mg in several studies. Eletriptan 20, 40 and 80mg significantly reduced the time lost away from usual activities as a result of migraine attacks compared with placebo, and at the higher doses (40 and 80mg) was superior to ergotamine/caffeine in this regard. Eletriptan is generally well tolerated, with the most common adverse events being asthenia, nausea, somnolence and dizziness, which are typical adverse effects of the triptans as a class. Adverse events increase modestly with increasing dose. The total incidences of adverse events with eletriptan 20 and 40mg are similar to those with sumatriptan 50 or 100mg, while the incidence with eletriptan 80mg is slightly higher than that with sumatriptan. Severe and serious adverse events are uncommon. Adverse event-related treatment discontinuation rates are low, generally <2-8%. The good tolerability of eletriptan is maintained during long-term use and the adverse event frequency may decrease with time.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Paul L. McCormack & Gillian M. Keating

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Correspondence to Paul L. McCormack.

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Various sections of the manuscript reviewed by: D. Deleu, Department of Neurology (Medicine), Hamad Medical Corporation, Doha, Qatar; S. Diamond, Diamond Headache Clinic, Chicago, Illinois, USA; A.J. Dowson, King’s College Headache Service, King’s College Hospital, London, UK; M. Färkkilä, Department of Neurology, University Hospital of Helsinki, Helsinki, Finland; G. Sandrini, Department of Neurological Rehabilitation, IRCCS C Mondino Foundation, Pavia, Italy; R. Stark, Neurology Department, Alfred Hospital, Melbourne, Victoria, Australia; S.J. Tepper, New England Center for Headache, Stamford, Connecticut, USA; N. Wells, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on eletriptan, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE search terms were ‘eletriptan’ or ‘UK 116044’. EMBASE search terms were ‘eletriptan’ or ‘UK 116044’. AdisBase search terms were ‘eletriptan’. Searches were last updated 20 May 2006.

Selection: Studies in adult patients with migraine who received eletriptan. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Eletriptan, migraine, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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McCormack, P.L., Keating, G.M. Eletriptan. Drugs 66, 1129–1149 (2006). https://doi.org/10.2165/00003495-200666080-00010

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