Eletriptan hydrochloride

Relpax (Pfizer)
40 mg and 80 mg film-coated tablets
Approved indication: migraine
Australian Medicines Handbook section 16.3.2

Naratriptan, sumatriptan and zolmitriptan are already available for the treatment of migraine. They are now joined by eletriptan, another serotonin (5-HT₁) agonist, which was originally approved for use in Australia in 2000.

Compared with sumatriptan, eletriptan is more lipophilic and has a higher bioavailability. Although at least 80% of the dose is rapidly absorbed, the absolute bioavailability of eletriptan is 50%. The maximum concentration is reached within two hours, but there is a delay if the drug is taken during a migraine attack.

Eletriptan acts on the 5-HT_1B receptors which control the constriction of intracranial blood vessels. It also acts on the 5-HT_1D and 5-HT_1F receptors of the trigeminal nerve.

The half-life of eletriptan is four hours. It is metabolised by the cytochrome P450 system. As CYP3A4 is involved, inhibitors of this enzyme, such as erythromycin or ketoconazole, will increase the plasma concentrations of eletriptan. Eletriptan is therefore contraindicated within 48 hours of treatment with a potent CYP3A4 inhibitor. It is also contraindicated in patients with severe hepatic impairment.

Although eletriptan is mainly eliminated by non-renal clearance, caution is still needed when prescribing for patients with renal impairment. This is because the increase in blood pressure caused by eletriptan is amplified in these patients. The vasoconstrictive effect of eletriptan contraindicates its use in patients with uncontrolled hypertension, coronary heart disease, cerebrovascular disease and peripheral vascular disease. Patients who are at risk of cardiac disease are recommended to have a cardiovascular evaluation before starting treatment with eletriptan. The drug should not be taken at the same time as an ergot alkaloid because of an additive effect on blood pressure.

Hypertension and chest pain are potential adverse effects. More common adverse effects include asthenia, nausea, dizziness and somnolence. The frequency of adverse effects increases with the dose.

The safety of eletriptan in pregnancy is uncertain. Small amounts are excreted in breast milk.

In clinical trials, 54–65% of patients responded within two hours to a dose of 40 mg eletriptan. The headache returned within 24 hours in 23% of patients. A second dose can be taken, if more than two hours have passed since the first dose. There is no point in taking a second dose if there was no response to the first dose.

More patients will respond within two hours to eletriptan than to sumatriptan. In one study 67% of 779 patients taking eletriptan 40 mg improved compared with 59% of 799 patients taking sumatriptan 100 mg. Both drugs were more effective than placebo, because only 26% of the 404 patients in the placebo group responded.¹

A company-supported meta-analysis has compared eletriptan and sumatriptan. There were 19 randomised placebo-controlled trials of the drugs involving several thousand patients. Compared to sumatriptan 100 mg, a mean of 9.1% more patients will obtain pain relief two hours after taking eletriptan 40 mg.²

Another analysis funded by the company compared eletriptan with other members of the class. The numbers of patients who needed to be treated for one to have a 24-hour sustained response were 3.6 for eletriptan 40 mg, 4.9 for sumatriptan 100 mg, 4.5 for zolmitriptan 5 mg and 5.7 for naratriptan 2.5 mg.³

Manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.