Pharmacology Update: Eletriptan Hydrochloride (Relpax—Pfizer)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Eletriptan is the newest "triptan" to be approved for the treatment of migraine headaches. It marks the seventh entry into this crowded market. Eletriptan, a selective 5-hydroxytryptamine (serotonin) 1B/1D receptor (5-HT1B, 5-HT1D) agonist will be marketed by Pfizer as "Relpax."
Eletriptan is indicated for the acute treatment of migraine with or without aura in adults.1
The initial dose of eletriptan is 20 mg or 40 mg. Results from clinical studies indicated a higher response rate with the 40-mg dose but individual response may vary.1 If the headache improves with the initial dose but returns, a second dose may be taken. The second dose should be taken at least 2 hours after the initial dose. If the initial dose is not effective, a second is not likely to be beneficial.1
Eletriptan is available as 20 mg and 40 mg tablets.
Eletriptan has high lipid solubility, favorable elimination half-life (4-6 hours), and good bioavailability (50%).1,2 In addition, it has slow dissociation from 5-HT1D receptors and very low affinity for 5-HT2 receptors in coronary arteries.2,3 In a comparative study, eletriptan was reported to be superior to sumatriptan in response at 2 hours.5 Headache responses ranged from 64-67% for eletriptan (40 mg-80 mg) vs 50-53% for sumatriptan (50 mg-100 mg). Pain-free response was 31-37% and 19-18%, respectively.
Eletriptan is metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4) and should not be used within at least 72 hours of any potent CYP3A4 inhibitors.1 These include ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir.
Eletriptan is the seventh "triptan" to be approved for the treatment of acute migraine headaches. It does not offer any single unique advantage but does possess favorable pharmacokinetic and pharmacodynamic properties including good lipid solubility, long elimination half-life (except for naratriptan and frovatriptan), good bioavailability, low affinity for 5-HT2 receptors of the coronary arteries, and slow dissociation from 5-HT1D receptors. In a phase III clinical trial (n = 1153), eletriptan 40 mg produced headache relief at 2 hours in 62% of patients, 65% for 80 mg, and 19% for placebo.4 Corresponding results for complete pain relief were 32%, 34%, and 3%, respectively. A lower recurrence rate, compared to placebo, was found with the 80-mg dose only. In 5 of 6 studies, the response (mild or no headache) rate ranged from 64.6% to 77.1% for the 80-mg dose, and 53.9% to 65% for the 40-mg dose.1 In the sixth study, the response rate was 61.4% for 40 mg and 58.6% for 80 mg. In a study of adolescents (n = 274), there were no statistical differences among treatment groups and placebo.1 Common side effects include asthenia, nausea, dizziness, paresthesia, and somnolence.1 These were higher for the 80 mg dose compared to the 40-mg dose (5-12% vs 3-7%).4 The approval of eletriptan was delayed as Pfizer had to address the FDA’s concerns about the cardiovascular safety of the higher dose.6 The 80-mg dose was ultimately not approved, and the recommended dose is now 20-40 mg. Side effects reported more frequently in patients receiving the 80-mg dose were asthenia and dizziness.7 The number needed to treat (NNT) were 9.9, 4.0, and 3.7 for 20 mg, 40 mg, and 80 mg, respectively. The corresponding number needed to harm (NNH) were 11, 7.0, and 3.7 for minor adverse effects.7 The wholesale cost for eletriptan (both strengths) is $12.64 per tablet and is comparable to other "triptans" such as sumatriptan 100 mg and rizatriptan 5 mg and 10 mg.
Eletriptan enters a crowded "triptan" market. It does not appear to provide any clinical advantage over currently available "triptans," particularly since the higher and more effective dose of eletriptan was not approved due to concern for adverse effects.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente and Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager at Kaiser Permanente in Oakland, CA.
1. Relpax Product Information. Pfizer, Inc, 2002.
2. Tfelt-Hansen P, et al. Drugs. 2000;60(6):1259-1287.
3. Napier C, et al. Eur J Pharmacol. 1999;368:259-268.
4. Stark R, et al. Cephalalgia. 2002;22:23-32.
5. Sandrini G, et al. Neurology. 2002;59:1210-1217.
6. FDC Reports. The Pink Sheet. 2003;65(1):5.
7. Smith LA, et al. Cochrane Systematic Review. 2002;4:1-27.