Generic Name: Eletriptan Hydrobromide
Class: Selective Serotonin 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
Introduction
Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).1 2 3 4 5 11 12 13 14 15
Uses for Relpax
Vascular Headaches
Acute treatment of migraine attacks with or without aura.1 2 3 4 5 6 7 15 16 17
Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.1
Safety and efficacy not established for management of cluster headaches.1
Relpax Dosage and Administration
Administration
Oral Administration
Administer orally without regard to meals.1 2 3 4 5 6 7 15 22
Administration not recommended within 72 hours of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir).1 (See Interactions.)
Dosage
Available as eletriptan hydrobromide; dosage expressed in terms of eletriptan.1
Adults
Vascular Headaches
Migraine
Oral
20 or 40 mg as a single dose;1 2 3 4 5 6 7 8 15 individualize dosage selection,1 weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 40-mg dose.1 3 In clinical studies, doses >40 mg were effective but were associated with increased risk of adverse effects.1 2
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.1
If patient does not respond to first dose, additional doses are unlikely to provide benefit for the same headache.1
Prescribing Limits
Adults
Vascular Headaches
Migraine
Oral
Maximum 40 mg as a single dose; do not exceed 80 mg in any 24-hour period.1
Safety of treating an average of >3 headaches per 30-day period has not been established.1
Special Populations
Hepatic Impairment
Dosage adjustment not necessary in patients with mild to moderate hepatic impairment.1 15 Contraindicated in those with severe hepatic impairment.1
Cautions for Relpax
Contraindications
Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).1
Coronary artery vasospasm (e.g., Prinzmetal variant angina).1
Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).1
Cerebrovascular syndromes (e.g., stroke syndrome, TIAs).1
Peripheral vascular ischemia (e.g., ischemic bowel disease).1
Hemiplegic or basilar migraine.1
Treatment within previous 24 hours with another 5-HT1 receptor agonist or ergot alkaloid.1 (See Specific Drugs under Interactions.)
Severe hepatic impairment (Child-Pugh grade C).1
Known hypersensitivity to eletriptan or any ingredient in the formulation.1
Warnings/Precautions
Warnings
Use only in patients in whom a clear diagnosis of migraine has been established.1
Interactions
Do not use within at least 72 hours of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir).1 (See Interactions.)
Cardiac Effects
Risk of coronary vasospasm, myocardial ischemia and/or infarction, life-threatening cardiac rhythm disturbances, and death with use of 5-HT1 receptor agonists.1
Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.1
Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician’s office, possibly followed by ECG) unless patient previously received the drug.1
Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.1
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.1
Cerebrovascular Events
Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal, with use of 5-HT1 receptor agonists.1
Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.1
Other Cardiovascular or Vasospastic Effects
Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported with use of 5-HT1 receptor agonists.1 Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic colitis, Raynaud’s phenomenon) occur following administration.1 19
Substantial increases in BP, including hypertensive crises, reported rarely with 5-HT1 receptor agonists in patients with or without history of hypertension.1 Transient increases in BP reported with eletriptan doses ≥60 mg; may be more pronounced in patients with renal impairment and geriatric patients.1
Increases in mean pulmonary artery pressure observed following administration of a 5-HT1 receptor agonist to patients with suspected CAD who were undergoing cardiac catheterization.1
Serotonin Syndrome
Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT1 receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs).1 21 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).1 21 (See Specific Drugs under Interactions.)
General Precautions
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.1
Specific Populations
Pregnancy
Category C.1
Lactation
Distributed into human milk.1 Caution advised if eletriptan is used.1
Pediatric Use
Safety and efficacy not established in children <18 years of age; use not recommended.1
Geriatric Use
No substantial differences in efficacy or safety relative to younger adults; however, limited clinical experience in patients ≥65 years of age.1 Increases in BP may be more pronounced.1
Hepatic Impairment
Contraindicated in patients with severe hepatic impairment.1
Renal Impairment
Increases in BP may be more pronounced.1
Common Adverse Effects
Asthenia,1 2 3 4 5 15 17 headache,1 4 17 nausea,1 2 3 4 5 15 17 paresthesia,1 2 3 15 dizziness,1 2 3 4 5 15 17 somnolence,1 3 4 5 15 17 dry mouth,1 4 17 flushing or feeling of warmth,1 pain/pressure sensations (i.e., chest pain [tightness/pressure], abdominal pain/discomfort/stomach pain/cramps/pressure),1 3 4 5 15 dyspepsia,1 dysphagia 1 17 (i.e., throat tightness,1 difficulty swallowing1 ).
Interactions for Relpax
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
Drug | Interaction | Comments |
|---|---|---|
Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine) | Potentially life-threatening serotonin syndrome1 21 | Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated1 19 20 21 |
Antifungals, azole (fluconazole, ketoconazole, itraconazole) | Increased peak plasma concentrations and AUC of eletriptan1 | Eletriptan administration not recommended within 72 hours of potent CYP3A4 inhibitors1 |
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide) | Additive vasospastic effects1 15 | Use within 24 hours contraindicated1 |
5-HT1 receptor agonists | Additive vasospastic effects1 15 | Use within 24 hours contraindicated1 |
HIV protease inhibitors (nelfinavir, ritonavir) | Potential increase in peak plasma concentrations and AUC of eletriptan1 | Eletriptan administration not recommended within 72 hours of potent CYP3A4 inhibitors1 |
Macrolide antibiotics (clarithromycin, erythromycin, troleandomycin) | Increased peak plasma concentrations and AUC of eletriptan1 | Eletriptan administration not recommended within 72 hours of potent CYP3A4 inhibitors1 |
MAO inhibitors | Pharmacokinetic interaction unlikely1 15 | |
Nefazodone | Potential increase in peak plasma concentrations and AUC of eletriptan1 | Eletriptan administration not recommended within 72 hours of potent CYP3A4 inhibitors1 |
Propranolol | Increased peak plasma concentrations and AUC of eletriptan;1 11 17 19 no increases in BP observed1 | No dosage adjustment required1 11 17 19 |
Verapamil | Increased peak plasma concentrations and AUC of eletriptan1 |
Relpax Pharmacokinetics
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
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).1
ActionsActions
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
Advice to Patients
Risk of dizziness or fatigue.1
Importance of immediately informing clinician if shortness of breath, tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck occurs and of not taking eletriptan again until evaluated by clinician.1
Importance of adhering to prescribed directions for use.1 Provide copy of manufacturer’s patient information.1
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
Importance of informing patients of risk of serotonin syndrome with concurrent use of eletriptan and an SSRI or SNRI.21 Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.21
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 20 mg (of eletriptan) | Relpax | Pfizer |
40 mg (of eletriptan) | Relpax | Pfizer |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Relpax 20MG Tablets (PFIZER U.S.): 6/$163.98 or 18/$473.96
Relpax 40MG Tablets (PFIZER U.S.): 6/$163.98 or 18/$473.96
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. Pfizer Inc. Relpax (eletriptan hydrobromide) prescribing information. New York, NY; 2006 Apr.
2. Goadsby PJ, Ferrari MD, Olesen J et al. Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan. Neurology. 2000; 54:156-63. [IDIS 441229] [PubMed 10636142]
3. Stark R, Dahlöf C, Haughie S et al. Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo-controlled study across three attacks. Cephalalgia. 2002; 22:23-32. [PubMed 11993610]
4. Diener HC, Jansen JP, Reches A et al. Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, radomised, double-blind, placebo-controlled comparison. Eur Neurol. 2002; 47:99-107. [PubMed 11844898]
5. Sandrini G, Färkkilä M, Burgess G et al. Eletriptan vs sumatriptan : a double-blind, placebo-controlled, multiple migraine attack study. Neurology. 2002; 59:1210-7. [IDIS 493948] [PubMed 12391349]
6. Smith LA, Oldman AD, McQuay HJ et al. Eletriptan for acute migraine. Cochrane Database Syst Rev. 2001; 3:CD003224.
7. Oldman AD, Smith LA, McQuay HJ et al. Pharmacological treatments for acute migraine: quantitative systematic review. Pain. 2002; 97:247-57. [IDIS 488670] [PubMed 12044621]
8. Ferrari MD, Goadsby PJ, Roon KI et al. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia. 2002; 22:633-58. [PubMed 12383060]
9. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. From American Academy of Neurology web site (http://www.aan.com).
10. Silberstein SD, for the US Headache Consortium. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2000; 55:754-63. [IDIS 453389] [PubMed 10993991]
11. Deleu D, Hanssens Y. Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000; 40:687-700. [IDIS 449430] [PubMed 10883409]
12. Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics, and efficacy. Drugs. 2000; 60:1259-87. [PubMed 11152011]
13. Tepper SJ, Rapoport AM, Sheftell FD. Mechanisms of action of the 5-HT1B/1D receptor agonists. Arch Neurol. 2002; 59:1084-8.. [PubMed 12117355]
14. Milton KA, Scott NR, Allen MJ et al. Pharmacokinetics, pharmacodynamics, and safety of the 5-HT1B/1D agonist eletriptan following intravenous and oral administration. J Clin Pharmacol. 2002; 42:528-39. [IDIS 480734] [PubMed 12017347]
15. Anon. Eletriptan (Relpax) for migraine. Med Lett Drugs Ther. 2003; 45:33-4.
16. Mathew NT, Schoenen J, Winner P et al. Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg. Headache. 2003; 43:214-22. [IDIS 496675] [PubMed 12603639]
17. Sheftell F, Ryan R, Pitman V, for the Eletriptan Steering Committee. Efficacy, safety, and tolerability of oral eletriptan for treatment of acute migraine: a multicenter, double-blind, placebo-controlled study conducted in the United States. Headache. 2003; 43:202-13. [IDIS 496674] [PubMed 12603638]
18. Fuseau E, Petricoul O, Sabin A et al. Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine. Clin Ther. 2001; 23:242-51. [IDIS 461622] [PubMed 11293557]
19. Pfizer Inc., New York, NY: Personal communication.
20. Eli Lilly and Company. Sarafem (fluoxetine hydrochloride) capsules prescribing information. Indainapolis, IN; 2000 Jul.
21. Food and Drug Administration. Public health advisory: combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephirne reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. Rockville, MD; 2006 Jul 19. From the FDA website: (, , and ).
22. Pfizer Inc. About Relpax—Best way to take Relpax. From the Pfizer website: () Accessed 2006 Dec 13.
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