Eletriptan

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St. John’s wort (Hypericum perforatum).

Serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) has been reported following concomitant treatment with triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenaline reuptake inhibitors (SNRIs). These reactions can be severe. If concomitant treatment with eletriptan and an SSRI or SNRI is clinically warranted, appropriate observation of the patient is advised, particularly during treatment initiation, with dose increases, or with addition of another serotonergic medication.

In clinical studies with erythromycin (1000 mg) and ketoconazole (400 mg), specific and potent inhibitors of CYP3A4, significant increases in eletriptan C_max (2 and 2.7-fold) and AUC (3.6 and 5.9-fold) respectively, were observed. This increased exposure was associated with an increase in eletriptan t_1/2 from 4.6 to 7.1 hours for erythromycin and from 4.8 to 8.3 hours for ketoconazole. Therefore, eletriptan should not be used together with potent CYP3A4 inhibitors e.g., ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin and protease inhibitors (ritonavir, indinavir and nelfinavir).

As the blood pressure effects of eletriptan are amplified in renal impairment, a 20 mg initial dose, is recommended in patients with mild or moderate renal impairment. The maximum daily dose should not exceed 40 mg.

For eletriptan no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. Eletriptan should be used during pregnancy only if clearly needed.

Eletriptan is excreted in human breast milk. In one study of 8 women given a single dose of 80 mg, the mean total amount of eletriptan in breast milk over 24 hours in this group was 0.02% of the dose. Nevertheless, caution should be exercised when considering the administration of eletriptan to women who are breast-feeding. Infant exposure can be minimised by avoiding breast-feeding for 24 hours after treatment.

Eletriptan has moderate influence on the ability to drive and use machines. Migraine or treatment with eletriptan may cause drowsiness or dizziness in some patients. Patients should be advised to evaluate their ability to perform complex tasks such as driving during migraine attacks and following administration of eletriptan.

Summary of the safety profile

Eletriptan has been administered in clinical trials to over 5000 subjects, taking one or two doses of eletriptan 20 or 40 or 80 mg. The most common adverse reactions noted were asthenia, somnolence, nausea and dizziness. In randomised clinical studies using doses of 20, 40 and 80 mg, a trend for a dose-dependency of the incidence of adverse events has been shown.

Tabulated list of adverse reactions

The following adverse reactions (with an incidence ≥1% and higher than placebo) were reported in patients treated with therapeutic doses in clinical trials. Events are categorized by frequency as common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), or rare (≥1/10,000 to <1/1,000).

The common adverse events seen with eletriptan are typical of adverse events reported with 5-HT1 agonists as a class.

In post-marketing experience, the following undesirable effects have been reported:

Immune system disorders: allergic reactions, some of which may be serious, including angioedema

Nervous system disorders: serotonin syndrome, rare cases of syncope, cerebrovascular accident

Vascular disorders: hypertension

Cardiac disorders: myocardial ischaemia or infarction, arteriospasm coronary

Gastrointestinal disorders: as with some other 5HT 1B/1D agonists, rare reports of ischaemic colitis have been received, vomiting.