Eletriptan Hydrobromide

Do not take eletriptan within 24 hours before or after using another migraine headache medicine, including:

• almotriptan (Axert), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt, Maxalt-MLT), sumatriptan (Imitrex, Treximet), or zolmitriptan (Zomig); or
• ergot medicine such as ergotamine (Ergomar, Cafergot, Migergot), dihydroergotamine (D.H.E. 45, Migranal), or methylergonovine (Methergine).

Do not use eletriptan within 72 hours before or after taking any of the following medicines:

• ketoconazole (Extina, Ketozole, Nizoral, Xolegal), itraconazole (Sporanox);
• nefazodone;
• clarithromycin (Biaxin); or
• ritonavir (Norvir, Kaletra), nelfinavir (Viracept).

Eletriptan may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

The following adverse reactions are described elsewhere in other sections of the prescribing information:

• Myocardial ischemia and myocardial infarction, and Prinzmetal's angina [see WARNINGS AND PRECAUTIONS]
• Arrhythmias [see WARNINGS AND PRECAUTIONS]
• Chest, throat, neck, and/or jaw pain/tightness/pressure [see WARNINGS AND PRECAUTIONS]
• Cerebrovascular events [see WARNINGS AND PRECAUTIONS]
• Other vasospasm reactions [see WARNINGS AND PRECAUTIONS]
• Medication overuse headache [see WARNINGS AND PRECAUTIONS]
• Serotonin syndrome [see WARNINGS AND PRECAUTIONS]
• Increase in blood pressure [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity reactions [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Among 4,597 patients who treated the first migraine headache with RELPAX in short-term placebocontrolled trials, the most common adverse reactions reported with treatment with RELPAX were asthenia, nausea, dizziness, and somnolence. These reactions appear to be dose-related.

In long-term open-label studies where patients were allowed to treat multiple migraine attacks for up to 1 year, 128 (8.3%) out of 1,544 patients discontinued treatment due to adverse reactions.

Table 1 lists adverse reactions that occurred in the subset of 5,125 migraineurs who received eletriptan doses of 20 mg, 40 mg and 80 mg or placebo in worldwide placebo-controlled clinical trials.

Only adverse reactions that were more frequent in a RELPAX treatment group compared to the placebo group with an incidence greater than or equal to 2% are included in Table 1.

Table 1: Adverse Reactions Incidence in Placebo-Controlled Migraine Clinical Trials : Reactions Reported by ≥ 2% Patients Treated with RELPAX and More Than Placebo

The frequency of adverse reactions in clinical trials did not increase when up to 2 doses of RELPAX were taken within 24 hours. The incidence of adverse reactions in controlled clinical trials was not affected by gender, age, or race of the patients. Adverse reaction frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (e.g., SSRIs, beta blockers, calcium channel blockers, tricyclic antidepressants), estrogen replacement therapy or oral contraceptives.

Postmarketing Experience

The following adverse reaction(s) have been identified during post approval use of RELPAX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Neurological: seizure

Digestive: vomiting

Read the entire FDA prescribing information for Relpax (Eletriptan hydrobromide)

Metabolized principally by CYP3A4.1

Little potential to inhibit or induce CYP1A2, CYP2C9, CYP2E1, or CYP3A4; pharmacokinetic interaction unlikely.1 Affects CYP2D6 only at high concentrations; eletriptan should not interfere with metabolism of other drugs when used at recommended dosages.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (increased peak plasma eletriptan concentrations and AUC) with concomitant use of CYP3A4 inhibitors.1 15 Eletriptan administration not recommended within 72 hours of potent CYP3A4 inhibitors.1

Specific Drugs

Absorption

Bioavailability

Well absorbed after oral administration.1 2 3 5 14 15 Absolute bioavailability is approximately 50%.1

Peak plasma concentrations attained approximately 1.5 and 2 hours after oral administration in healthy adults and patients with moderate to severe migraine, respectively.1 2 5 14 15

Food

High-fat meal increases AUC and peak plasma concentrations by approximately 20–30%.1

Distribution

Extent

Distributed into human milk.1

Plasma Protein Binding

Approximately 85%.1

Elimination

Metabolism

Metabolized principally by CYP3A4.1 8 11 15 N-demethylated metabolite (only known active metabolite) does not appear to contribute substantially to overall effect of parent drug.1 19

Elimination Route

Renal clearance accounts for about 10% of total clearance.1

Half-life

Approximately 4 hours.1 2 3 14 15

Special Populations

In patients with mild to moderate hepatic impairment, peak plasma eletriptan concentrations and AUC are increased 18 and 34%, respectively.1 Not studied in patients with severe hepatic impairment.1

In patients with renal impairment, no substantial changes in clearance.1

In geriatric patients, pharmacokinetic profile is similar to that in younger adults, although half-life may be increased.1

• Binds with high affinity to 5-HT1B and 5-HT1D receptors.1 2 3 4 5 11 12 13 14 15

• Structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists (e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan).11 12

• Precise mechanism of action not established; may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.1 8 11 12 13

• Risk of dizziness or fatigue.1 24

• Risk of serious cardiovascular or cerebrovascular events (e.g., MI, stroke) or other vasospastic reactions.1 Importance of seeking medical care if symptoms of such reactions (e.g., shortness of breath, weakness, slurring of speech, or tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck) occur and of not taking eletriptan again until evaluated by clinician.1 23 24

• Importance of adhering to prescribed directions for use.24 Provide copy of manufacturer’s patient information.1 24

• Overuse of drugs indicated for the management of acute migraine attacks may exacerbate headaches;1 24 importance of recording headache frequency and drug use to monitor effectiveness of treatment.31

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).1 24

• Importance of informing patients of risk of serotonin syndrome, particularly with concurrent use of eletriptan and an SSRI or SNRI.1 21 24 Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.21 24

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 24

• Importance of informing patients of other important precautionary information.1 (See Cautions.)