Eletriptan (Monograph)

Brand name: Relpax
Drug class: Selective Serotonin Agonists
- Antimigraine Agents
- Selective Vascular Serotonin Type 1-Like Receptor Agonists
- 5-HT1 Agonists
VA class: CN105
Chemical name: 3-[[(R)-1-Methyl-2-pyrrolidinyl]methyl]-5-[2-(phenylsulfonyl)ethyl]indole
Molecular formula: C₂₂H₂₆N₂O₂S
CAS number: 143322-58-1

Medically reviewed by Drugs.com on Jul 22, 2024. Written by ASHP.

Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).

Uses for Eletriptan

Vascular Headaches

Acute treatment of migraine attacks with or without aura.

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.

Safety and efficacy not established for management of cluster headaches.

Eletriptan Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.

Administration not recommended within 72 hours of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir). (See Interactions.)

Dosage

Available as eletriptan hydrobromide; dosage expressed in terms of eletriptan.

Adults

Vascular Headaches

Migraine

Oral

20 or 40 mg as a single dose; individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 40-mg dose. In clinical studies, doses >40 mg were effective but were associated with increased risk of adverse effects.

If headache recurs, additional doses may be administered at intervals of ≥2 hours, up to a maximum dosage of 80 mg in any 24-hour period.

If patient does not respond to first dose, additional doses are unlikely to provide benefit for the same headache.

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 40 mg as a single dose; do not exceed 80 mg in any 24-hour period.

Safety of treating an average of >3 headaches per 30-day period has not been established.

Special Populations

Hepatic Impairment

Dosage adjustment not necessary in patients with mild to moderate hepatic impairment. Contraindicated in those with severe hepatic impairment.

Cautions for Eletriptan

Contraindications

• Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).

• Coronary artery vasospasm (e.g., Prinzmetal variant angina).

• Uncontrolled hypertension.

• Other serious underlying cardiovascular disease.

• Cerebrovascular syndromes (e.g., stroke syndrome, TIAs).

• Peripheral vascular ischemia or ischemic bowel disease.

• Hemiplegic or basilar migraine.

• Treatment within previous 24 hours with another 5-HT₁ receptor agonist or ergot alkaloid. (See Specific Drugs under Interactions.)

• Severe hepatic impairment (Child-Pugh grade C).

• Known hypersensitivity to eletriptan or any ingredient in the formulation.

Warnings/Precautions

Careful Diagnosis of Migraine

Use only in patients in whom a clear diagnosis of migraine has been established.

Exclude other potentially serious neurologic disorders before administering eletriptan to patients not previously diagnosed with migraine or to those with atypical symptoms.

Interactions with CYP3A4 Inhibitors

Do not use within at least 72 hours of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir). (See Interactions.)

Cardiac Effects

Possible myocardial ischemia and/or infarction and coronary vasospasm, even in patients without a history of CAD. Contraindicated in patients with ischemic or vasospastic heart disease.

Possible fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation). Discontinue if such disturbances occur.

Tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently but usually are noncardiac in origin. Manufacturer states that patients with symptoms suggestive of angina after receiving eletriptan should be evaluated for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; if administration is resumed and such signs or symptoms recur, ECG evaluation recommended.

Patients at Risk for CAD

Perform cardiovascular evaluation prior to initiating therapy in patients with multiple cardiovascular risk factors (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of CAD) who have not previously received 5-HT₁ receptor agonist therapy.

If evaluation provides evidence of CAD or coronary vasospasm, do not administer the drug.

If results of evaluation are satisfactory, consider administering the initial dose in a medically supervised setting followed immediately by an ECG.

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage and stroke, sometimes fatal. (See Careful Diagnosis of Migraine under Cautions.) Discontinue therapy if a cerebrovascular event occurs.

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.

Other Vasospastic Effects

Possible noncoronary vasospastic reactions (e.g., peripheral vascular ischemia, GI ischemia and infarction with abdominal pain and bloody diarrhea, splenic infarction, Raynaud’s syndrome); transient or permanent blindness and partial vision loss reported in patients receiving 5-HT₁ receptor agonists.

If signs or symptoms suggestive of vasospasm occur following administration, evaluate patient to rule out vasospastic reaction before administering additional doses.

Hypertensive Effects

Substantial increases in BP, including hypertensive crisis with acute impairment of organ systems, reported rarely with 5-HT₁ receptor agonists in patients with or without history of hypertension. Transient increases in BP reported with eletriptan doses ≥60 mg; may be more pronounced in patients with renal impairment and geriatric patients.

Increases in mean pulmonary arterial pressure observed following administration of a 5-HT₁ receptor agonist to patients with suspected CAD who were undergoing cardiac catheterization.

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported in patients receiving 5-HT₁ receptor agonists, particularly in those receiving SSRIs or SNRIs concomitantly. (See Specific Drugs under Interactions.) Also may occur in patients receiving MAO inhibitors or tricyclic antidepressants concomitantly.

Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

If manifestations of serotonin syndrome occur, discontinue treatment with eletriptan and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.

Medication Overuse Headache

Overuse of drugs indicated for management of acute migraine attacks (e.g., use of 5-HT₁ receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for ≥10 days per month) may result in migraine-like daily headaches or a marked increase in frequency of migraine attacks.

Detoxification, including withdrawal of overused drugs; treatment of withdrawal symptoms (e.g., transient worsening of headaches); and consideration of prophylactic migraine therapy may be necessary.

Sensitivity Reactions

Serious allergic reactions (e.g., angioedema) reported.

Ocular Effects

Possible accumulation of eletriptan and/or its metabolites in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into human milk. Caution advised if eletriptan is used.

Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.

Geriatric Use

No substantial differences in efficacy or safety relative to younger adults; however, limited clinical experience in patients ≥65 years of age. Increases in BP may be more pronounced.

Hepatic Impairment

Contraindicated in patients with severe hepatic impairment.

Renal Impairment

Increases in BP may be more pronounced.

Common Adverse Effects

Asthenia, headache, nausea, paresthesia, dizziness, somnolence, dry mouth, flushing or feeling of warmth, pain/pressure sensations (i.e., chest pain [tightness/pressure], abdominal pain/discomfort/stomach pain/cramps/pressure), dyspepsia, dysphagia (i.e., throat tightness, difficulty swallowing ).

Drug Interactions

Metabolized principally by CYP3A4.

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

Drugs Affecting Hepatic Microsomal Enzymes

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

Specific Drugs

Eletriptan Pharmacokinetics

Absorption

Bioavailability

Well absorbed after oral administration. Absolute bioavailability is approximately 50%.

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

Food

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

Distribution

Extent

Distributed into human milk.

Plasma Protein Binding

Approximately 85%.

Elimination

Metabolism

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

Elimination Route

Renal clearance accounts for about 10% of total clearance.

Half-life

Approximately 4 hours.

Special Populations

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

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

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

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Actions

• Binds with high affinity to 5-HT_1B and 5-HT_1D receptors.

• Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan).

• 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.

Advice to Patients

• Risk of dizziness or fatigue.

• Risk of serious cardiovascular or cerebrovascular events (e.g., MI, stroke) or other vasospastic reactions. 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.

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

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

• 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).

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

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

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

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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