Relpax Drug Interactions

Effect of Other Medicinal Products on Eletriptan: In the pivotal clinical trials of eletriptan no evidence of interaction with beta-blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors and flunarizine was reported but data from formal clinical interaction studies with these medicinal products are not available (other than propranolol, see Interaction with serotonergic active drugs as follows).
Population pharmacokinetic analysis of clinical studies has suggested that the following medicinal products (beta-blockers, tricyclic antidepressants, selective serotonin re-uptake inhibitors, estrogen based hormone replacement therapy, estrogen containing oral contraceptives and calcium channel blockers) are unlikely to have an effect on the pharmacokinetic properties of eletriptan (see Interaction with Serotonergic Active Drugs as follows).
Eletriptan is not a substrate for monoamine oxidase (MAO). There is no expectation of a pharmacokinetic interaction between eletriptan and MAO inhibitors, therefore no formal interaction study has been undertaken.
In clinical studies with propranolol (160 mg), verapamil (480 mg) and fluconazole (100 mg) the C_max of eletriptan was increased 1.1 fold, 2.2 fold and 1.4 fold, respectively. The increase in eletriptan’s AUC being 1.3 fold, 2.7 fold and 2.0 fold, respectively.
These effects are not considered clinically significant as there were no associated increases in blood pressure or adverse events compared to administering eletriptan alone.
In clinical studies with erythromycin (1,000 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 with erythromycin and from 4.8 to 8.3 hours with ketoconazole (see Pharmacology: Pharmacokinetics under Actions). 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).
In clinical studies with oral caffeine/ergotamine administered 1 and 2 hours after eletriptan, minor though additive increases in blood pressure were observed which are predictable based on the pharmacology of the two drugs. Therefore, it is recommended that either ergotamine-containing or ergot-type medications (e.g. dihydroergotamine) should not be taken within 24 hours of eletriptan dosing. Conversely, at least 24 hours should elapse after the administration of an ergotamine-containing preparation before eletriptan is given.
Effect of Eletriptan on Other Medicinal Products: There is no in vitro or in vivo evidence that clinical doses of eletriptan will inhibit or induce cytochrome P450 enzymes, including CYP3A4 drug metabolizing enzymes. Therefore, it is considered that eletriptan is unlikely to cause clinically important drug interactions mediated by these enzymes.
Interaction with Serotonergic Active Drugs: Co-administration of 5-HT agonists, including eletriptan, with drugs having serotonergic activity, such as SSRIs and SNRIs, may increase the risk of serotonin syndrome. If concomitant treatment with eletriptan and a serotonergic active drug is clinically warranted, caution is advised. Careful observation of the patient is warranted particularly during treatment initiation or dose increase of either drug (see Precautions).