Amerge

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

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

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

  • Uncontrolled hypertension.1

  • Other serious underlying cardiovascular disease.1

  • Cerebrovascular syndromes (e.g., stroke syndrome, TIAs).1

  • Peripheral vascular disease or ischemic bowel disease.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

Careful Diagnosis of Migraine

Use only in patients in whom a clear diagnosis of migraine has been established.1

If a given migraine attack fails to respond to the first dose of naratriptan, reconsider diagnosis before administering a second dose.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

Possible myocardial ischemia and/or infarction and coronary vasospasm, even in patients without a history of CAD.1 12 Contraindicated in patients with ischemic or vasospastic heart disease.1

Possible fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation).1 12 Discontinue if such disturbances occur.12

Tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently but usually are noncardiac in origin.1 12 Manufacturer states that 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 is resumed and such signs or symptoms recur, ECG evaluation recommended.1

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.1 12

If evaluation provides evidence of CAD or coronary vasospasm, do not administer the drug.1

If results of evaluation are satisfactory, consider administering the initial dose in a medically supervised setting followed immediately by an ECG.1 12

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD who are receiving intermittent long-term therapy.1

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage and stroke, sometimes fatal.1 12 (See Careful Diagnosis of Migraine under Cautions.) Discontinue therapy if a cerebrovascular event occurs.1 12

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.1

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);1 12 transient or permanent blindness and partial vision loss reported in patients receiving 5-HT1 receptor agonists.12

If signs or symptoms suggestive of vasospasm occur following administration, evaluate patient to rule out vasospastic reaction before administering additional doses.1 12

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;1 12 increases may be more pronounced in geriatric patients and patients with hypertension.1

Increases in mean pulmonary arterial 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 in patients receiving 5-HT1 receptor agonists, particularly in those receiving SSRIs or SNRIs concomitantly.1 10 (See Specific Drugs under Interactions.) Also may occur in patients receiving MAO inhibitors or tricyclic antidepressants concomitantly.12

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

If manifestations of serotonin syndrome occur, discontinue naratriptan and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.1 33

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.1 31 32

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.1 31 32

Sensitivity Reactions

Possible hypersensitivity reactions, including anaphylaxis or anaphylactoid reactions; may be life-threatening or fatal.1

Specific Populations

Pregnancy

Category C.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 initiated10

Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide [no longer commercially available in the US])

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

Actions

  • 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

  • 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 naratriptan again until evaluated by clinician.1 12

  • 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

  • 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.1 31

  • 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, particularly 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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Naratriptan Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

1 mg (of naratriptan)*

Amerge

GlaxoSmithKline

Naratriptan Hydrochloride Tablets

2.5 mg (of naratriptan)*

Amerge

GlaxoSmithKline

Naratriptan Hydrochloride Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. 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/$290.00 or 27/$829.95

Amerge 2.5MG Tablets (GLAXO SMITH KLINE): 9/$304.00 or 27/$885.00

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 31, 2013. 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; 2012 Mar.

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]

12. Merck and Co., Inc. Maxalt (rizatriptan benzoate) tablets and Maxalt-MLT (rizatriptan benzoate) orally disintegrating tablets prescribing information. Whitehouse Station, NJ; 2013 Jan.

31. Tepper SJ, Tepper DE. Breaking the cycle of medication overuse headache. Cleve Clin J Med. 2010; 77:236-42. [PubMed 20360117]

32. Negro A, Martelletti P. Chronic migraine plus medication overuse headache: two entities or not?. J Headache Pain. 2011; 12:593-601. [PubMed 21938457]

33. Bijl D. The serotonin syndrome. Neth J Med. 2004; 62:309-13. [PubMed 15635814]

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