Generic Name: Naratriptan Hydrochloride
Class: Selective Serotonin Agonists
VA Class: CN105
Chemical Name: N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide monohydrochloride
Molecular Formula: C17H25N3O2S•HCl
CAS Number: 143388-64-1
Introduction
Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).1 2 3 11
Uses for Amerge
Vascular Headaches
Acute treatment of migraine attacks with or without aura.1
Not recommended for management of hemiplegic or basilar migraine or for the prophylaxis of migraine.1
Safety and efficacy not established for management of cluster headaches.1
Amerge Dosage and Administration
Administration
Oral Administration
Administer orally with fluids.1
Dosage
Available as naratriptan hydrochloride; dosage is expressed in terms of naratriptan.1
Adults
Vascular Headaches
Migraine
Oral
1 or 2.5 mg as a single dose;1 individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 2.5-mg dose.1
If headache recurs or only a partial response is achieved, may repeat dose once after 4 hours.1
Following failure to respond to the first dose, reconsider diagnosis of migraine prior to administration of a second dose.1
Prescribing Limits
Adults
Vascular Headaches
Migraine
Oral
Maximum 5 mg in any 24-hour period.1
Safety of treating an average of >4 headaches per 30-day period not established.1
Special Populations
Hepatic Impairment
Contraindicated in patients with severe hepatic impairment.1 In patients with mild or moderate hepatic impairment, reduce initial dosage; maximum dosage of 2.5 mg per 24-hour period is recommended.1
Renal Impairment
Contraindicated in patients with severe renal impairment.1 In patients with mild or moderate renal impairment, reduce initial dosage; maximum dosage of 2.5 mg per 24-hour period is recommended.1
Cautions for Amerge
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 colitis).1
Severe hepatic impairment (e.g., Child-Pugh grade C).1
Severe renal impairment (e.g., Clcr ≤15 mL/minute).1
Hemiplegic or basilar migraine.1
Treatment within previous 24 hours with another 5-HT1 receptor agonist or an ergot alkaloid.1 (See Specific Drugs under Interactions.)
Known hypersensitivity to naratriptan 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
Exclude other potentially serious neurologic disorders before administering naratriptan to patients not previously diagnosed with migraine or to those with atypical symptoms.1
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, 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 a satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician’s office, possibly followed by an ECG) unless patient previously received the drug.1
Periodic cardiovascular evaluation recommended in patients with risk factors for CAD who are receiving intermittent long-term therapy.1
Patients with symptoms suggestive of angina after receiving naratriptan should be evaluated for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses.1 If administration resumed and such signs or symptoms recur, ECG evaluation recommended.1
Cerebrovascular Events
Possible cerebral or subarachnoid hemorrhage, stroke, and other adverse 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.1 Further evaluation for atherosclerosis or predisposition to vasospasm recommended if signs or symptoms of decreased arterial flow (e.g., ischemic colitis, Raynaud’s syndrome) occur following administration.1
Substantial increases in BP, including hypertensive crises, reported rarely with 5-HT1 receptor agonists in patients with or without history of hypertension; increases may be more pronounced in geriatric patients and patients with hypertension.1
Increases in mean pulmonary artery pressure and mean aortic pressure observed following naratriptan administration in 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 10 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 10 (See Specific Drugs under Interactions.)
Sensitivity Reactions
Possible hypersensitivity reactions, including anaphylaxis or anaphylactoid reactions; may be life-threatening or fatal.1
General Precautions
Ocular Effects
Possible accumulation of naratriptan 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 Pregnancy Registry at 800-336-2176.1
Lactation
Naratriptan and/or its metabolites are distributed into milk in rats.1 Caution advised if naratriptan is used.1
Pediatric Use
Safety and efficacy not established in children <18 years of age.1
Geriatric Use
Use not recommended.1 Increased risk of CAD in this patient population.1 Possible increased risk of adverse effects in those with renal or hepatic impairment.1 8 More pronounced increases in BP possible in geriatric patients.1
Hepatic Impairment
Use with caution.1 (See Hepatic Impairment under Dosage and Administration and also Special Populations under Pharmacokinetics.) Contraindicated in patients with severe hepatic impairment.1 (See Cautions.)
Renal Impairment
Use with caution.1 (See Renal Impairment under Dosage and Administration and also Special Populations under Pharmacokinetics.) Contraindicated in patients with severe renal impairment.1 (See Cautions.)
Common Adverse Effects
Paresthesia,1 nausea,1 4 7 dizziness,1 drowsiness,1 malaise/fatigue,1 and throat/neck symptoms (e.g., pain, pressure).1
Interactions for Amerge
Metabolized by a wide range of CYP isoenzymes.1
Does not inhibit MAO enzymes and is a poor inhibitor of CYP isoenzymes; pharmacokinetic interactions with drugs metabolized by CYP or MAO unlikely.1
Smoking
Potential pharmacokinetic interaction (increased naratriptan clearance).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 10 | Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated1 10 |
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide) | Possible additive vasospastic effects1 | Use within 24 hours contraindicated1 |
5-HT1 receptor agonists | Possible additive vasospastic effects1 | Use within 24 hours contraindicated1 |
Oral contraceptives | Possible slightly increased plasma concentrations of naratriptan1 |
Amerge Pharmacokinetics
Absorption
Bioavailability
Well absorbed, with oral bioavailability of about 70%.1
Peak plasma concentrations attained within 2–3 hours after oral administration.1 Absorption may be slower during a migraine attack, with peak plasma concentrations attained in 3–4 hours.1
Food
Food does not affect pharmacokinetics of naratriptan.1
Distribution
Extent
Distributed into milk in animals.1
Plasma Protein Binding
28–31%.1
Elimination
Metabolism
In vitro, metabolized by a wide range of CYP isoenzymes into inactive metabolites.1
Elimination Route
Eliminated principally in urine, with approximately 50% of a dose excreted as unchanged drug and 30% as metabolites.1
Half-life
6 hours.1
Special Populations
In patients with moderate hepatic impairment (Child-Pugh grade A or B), clearance is decreased by approximately 30% .1
In patients with moderate renal impairment (Clcr of 18–39 mL/minute), clearance is decreased by approximately 50%.1
Stability
Storage
Oral
Tablets
20–25°C.1 Protect from heat and light.1
ActionsActions
Binds with high affinity to 5-HT1B and 5-HT1D.1 11
Structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, rizatriptan, sumatriptan, zolmitriptan).1 2 11
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 the trigeminal pain pathway.1 2 3
Advice to Patients
Importance of informing clinicians of any atypical migraine symptoms.1 8
Importance of immediately informing clinician if tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck occurs and of not taking naratriptan again until evaluated by clinician.1
Importance of informing clinician immediately if sudden and/or severe abdominal pain occurs.1
Importance of taking naratriptan exactly as prescribed.1
Importance of providing a copy of manufacturer’s patient information.1
Importance of informing clinicians 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 10
Importance of informing patients of risk of serotonin syndrome with concurrent use of naratriptan and an SSRI or SNRI.1 10 Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.1 10
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 | 1 mg (of naratriptan) | Amerge | GlaxoSmithKline |
2.5 mg (of naratriptan) | Amerge | GlaxoSmithKline |
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.
Amerge 1MG Tablets (GLAXO SMITH KLINE): 9/$290 or 27/$829.95
Amerge 2.5MG Tablets (GLAXO SMITH KLINE): 9/$292 or 27/$850.96
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 June 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. GlaxoSmithKline. Amerge (naratriptan hydrochloride) tablets prescribing information. Research Triangle Park, NC; 2006 Jun.
2. Goadsby PJ, Hargreaves RJ. Mechanisms of action of serotonin 5-HT1B/1Dagonists: insights into migraine pathophysiology using rizatriptan. Neurology. 2000; 55(Suppl 2):S8-S14. [IDIS 455607] [PubMed 11089513]
3. Dulli DA. Naratriptan: an alternative for migraine. Ann Pharmacother. 1999; 33:704-11. [IDIS 428251] [PubMed 10410185]
4. Klassen A, Elkind A, Asgharnejad M et al. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled parallel-group study. Headache. 1997; 37:640-5. [PubMed 9439085]
5. 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 ().
6. 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]
7. Mathew NT, Asgharnejad M, Peykamian M et al. Naratriptan is effective and well tolerated in the acute treatment of migraine: results of a double-blind, placebo-controlled, crossover study. Neurology. 1997; 49:1485-90. [IDIS 398099] [PubMed 9409334]
8. GlaxoSmithKline, Research Triangle Park, NC; Personal communication.
9. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacologic management of acute attacks. St. Paul, MN; 2001. From the American Academy of Neurology web site: ()
10. 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 ).
11. 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]
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