Amerge

— THERAPEUTIC CATEGORIES —
  • Migraine and headache
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Amerge Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Naratriptan (as HCl) 1mg, 2.5mg; tabs.

    Pharmacological Class

    Selective 5-HT1B/1D receptor agonist.

    How Supplied

    Tabs—9

    How Supplied

    Amerge supplied as:

    • 1 mg, are white, D-shaped, film-coated tablets debossed with “GX CE3” on one side in blister packs of 9 tablets.
    • 2.5 mg, are green, D-shaped, film-coated tablets debossed with “GX CE5” on one side in blister packs of 9 tablets. 

    Storage

    Store at controlled room temperature, 20° to 25° C (68° to 77° F).

    Manufacturer

    GlaxoSmithKline

    Generic Availability

    YES

    Amerge Indications

    Indications

    Acute treatment of migraine with or without aura. 

    Limitations of Use

    Use only after a clear diagnosis of migraine has been established. Not indicated for the prevention of migraine attacks. Safety and effectiveness of Amerge have not been established for cluster headache.

    Amerge Dosage and Administration

    Adult

    ≥18yrs: 1mg or 2.5mg with fluids; may repeat once after 4hrs; max 5mg/24hrs. The safety of treating, on average, more than 4 headaches in a 30-day period has not been established. Mild to moderate renal or hepatic impairment: initially 1mg; max 2.5mg/24hrs.

    Children

    <18yrs: not recommended.

    Amerge Contraindications

    Contraindications

    Ischemic coronary artery disease (angina pectoris, history of MI, or documented silent ischemia) or vasospasm, including Prinzmetal's angina. Wolff-Parkinson-White syndrome. Arrhythmias associated with other cardiac accessory conduction pathway disorders. History of stroke, TIA, or basilar or hemiplegic migraine. Peripheral vascular disease. Ischemic bowel disease. Uncontrolled hypertension. Within 24hrs of other 5-HT1 agonists or ergot-type drugs. Severe renal or hepatic impairment.

    Amerge Boxed Warnings

    Not Applicable

    Amerge Warnings/Precautions

    Warnings/Precautions

    Confirm diagnosis. Exclude underlying cardiovascular disease, supervise 1st dose, and consider monitoring ECG in patients with likelihood of unrecognized coronary disease (eg, increased age, hypertension, obesity, diabetes, smokers, strong family history). Monitor cardiovascular function in long-term intermittent use. Discontinue if arrhythmias, cerebrovascular events, or serotonin syndrome occur. Possible peripheral or GI vascular ischemia, splenic infarction, or Raynaud's syndrome following use of 5-HT1 agonists. Monitor BP during treatment. Hepatic or renal dysfunction. Elderly (monitor). Pregnancy. Nursing mothers.

    Warnings/Precautions

    Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina

    • Amerge is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of Amerge. 
    • Amerge may cause coronary artery vasospasm (Prinzmetal’s angina) even in patients without a history of CAD.
    • Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving Amerge. 
    • For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of Amerge in a medically supervised setting and performing an electrocardiogram (ECG) immediately following Amerge administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of Amerge. 

    Arrhythmias 

    • Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue Amerge if these disturbances occur. 
    • Amerge is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

    Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure 

    • Sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw commonly occur after treatment with Amerge and are usually non-cardiac in origin. Perform a cardiac evaluation if these patients are at high cardiac risk. 
    • 5-HT1 agonists, including Amerge, are contraindicated in patients with CAD and those with Prinzmetal’s variant angina. 

    Cerebrovascular Events 

    • Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. 
    • Patients with migraine may be at increased risk of certain cerebrovascular events (eg, stroke, hemorrhage, TIA). Discontinue Amerge if a cerebrovascular event occurs. 
    • Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, exclude other potentially serious neurological conditions. Amerge is contraindicated in patients with a history of stroke or TIA.

    Other Vasospasm Reactions 

    • Amerge may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome. 
    • In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional doses of Amerge. 
    • Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists; may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.

    Medication Overuse Headache 

    • Overuse of acute migraine drugs (eg, ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). 
    • Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. 
    • Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

    Serotonin Syndrome 

    • Serotonin syndrome may occur with Amerge, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors.
    • Serotonin syndrome symptoms may include mental status changes, autonomic instability, neuromuscular aberrations, and/or gastrointestinal symptoms. 
    • The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. 
    • Discontinue Amerge if serotonin syndrome is suspected.

    Increase in Blood Pressure 

    • Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. 
    • Monitor blood pressure in patients treated with Amerge. 
    • Amerge is contraindicated in patients with uncontrolled hypertension.

    Anaphylactic Reactions 

    • Reports of anaphylaxis and hypersensitivity reactions, including angioedema, have occurred in those receiving Amerge; these reactions can be life threatening or fatal. 
    • In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. 
      Amerge is contraindicated in patients with a history of hypersensitivity reaction to Amerge.

    Pregnancy Considerations

    There is no adequate data on the developmental risk associated with use of Amerge in pregnant women. Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have documented outcomes in women exposed to naratriptan during pregnancy; however, due to small sample sizes, no definitive conclusions can be drawn regarding the risk of birth defects following exposure to naratriptan.

    Nursing Mother Considerations

    There is no data on the presence of naratriptan in human milk, the effects of naratriptan on the breastfed infant, or the effects of naratriptan on milk production. Naratriptan is present in rat milk. 

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Amerge and any potential adverse effects on the breastfed infant from naratriptan or from the underlying maternal condition.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established. Therefore, Amerge is not recommended for use in patients <18 years of age.

    Geriatric Considerations

    Clinical trials of Amerge did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 

    In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. 

    Naratriptan is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in elderly patients who have reduced renal function. In addition, elderly patients are more likely to have decreased hepatic function, they are at higher risk for CAD, and blood pressure increases may be more pronounced in the elderly.  A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (eg, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving Amerge.

    Renal Impairment Considerations

    The use of Amerge is contraindicated in patients with severe renal impairment (creatinine clearance: <15 mL/min) because of decreased clearance of the drug.

    Hepatic Impairment Considerations

    The use of Amerge is contraindicated in patients with severe hepatic impairment (Child-Pugh Grade C) because of decreased clearance.

    Amerge Pharmacokinetics

    Absorption

    Naratriptan is well absorbed, with about 70% oral bioavailability. Following administration of a 2.5-mg tablet, the peak concentrations are obtained in 2 to 3 hours.

    Distribution

    The steady-state volume of distribution of naratriptan is 170 L. Plasma protein binding is 28% to 31% over the concentration range of 50 to 1,000 ng/mL.

    Metabolism

    In vitro, naratriptan is metabolized by a wide range of cytochrome P450 isoenzymes into a number of inactive metabolites. 

    Elimination

    Naratriptan is predominantly eliminated in urine, with 50% of the dose recovered unchanged and 30% as metabolites in urine. The mean elimination half-life of naratriptan is 6 hours.

    Amerge Interactions

    Interactions

    Methysergide, other ergotamines, or other 5-HT1 agonists: see Contraindications. Serotonin syndrome with SSRIs, SNRIs, TCAs, or MAOIs.

    Amerge Adverse Reactions

    Adverse Reactions

    Paresthesias, nausea, dizziness, drowsiness, malaise/fatigue, throat/neck symptoms (pain, pressure, tightness), drug overuse headache (discontinue if occurs); rare: serious cardiac events, anaphylactoid reactions.

    Amerge Clinical Trials

    Clinical Trials

    The efficacy of Amerge in the acute treatment of migraine headaches was evaluated in 3 randomized, double-blind, placebo-controlled trials in adult patients (Trials 1, 2, 3). 

    In all studies, patients were instructed to treat at least 1 moderate to severe headache. Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 4 hours after dosing. Associated symptoms such as nausea, vomiting, photophobia, and phonophobia were also assessed. 
    Maintenance of response was assessed for up to 24 hours postdose. 
    A second dose of Amerge or other rescue medication to treat migraines was allowed 4-24 hours after the initial treatment for recurrent headache. 

    In all 3 trials, the percentage of patients achieving headache response 4 hours after treatment, the primary outcome measure, was significantly greater among patients receiving Amerge compared with those who received placebo.

    In all trials, response to 2.5 mg was numerically greater than response to 1 mg and in the largest of the 3 trials, there was a statistically significant greater percentage of patients with headache response at 4 hours in the 2.5-mg group compared with the 1-mg group. The results are summarized below.

    • Trial 1:
      • Amerge 1 mg (n=491) = 50% (P <0.05 compared with placebo)
      • Amerge 2.5 mg (n=493) = 60% (P <0.05 compared with placebo)
      • Placebo (n=395) = 34%
    • Trial 2:
      • Amerge 1 mg (n=491) = 52% (P <0.05 compared with placebo)
      • Amerge 2.5 mg (n=493) = 66% (P <0.05 compared with placebo and compared with 1 mg)
      • Placebo (n=395) = 27%
    • Trial 3:
      • Amerge 1 mg (n=491) = 54% (P <0.05 compared with placebo)
      • Amerge 2.5 mg (n=493) = 65% (P <0.05 compared with placebo)
      • Placebo (n=395) = 32%

    There is no evidence that doses of 5 mg provided a greater effect than 2.5 mg. There was no evidence to suggest that treatment with Amerge was associated with an increase in the severity or frequency of migraine attacks. The efficacy of Amerge was unaffected by presence of aura; gender, age, or weight of the subject; oral contraceptive use; or concomitant use of common migraine prophylactic drugs (eg, beta-blockers, calcium channel blockers, tricyclic antidepressants). There was insufficient data to assess the impact of race on efficacy.

    Amerge Note

    Notes

    Register pregnant patients exposed to naratriptan by calling (800) 336-2176.

    Amerge Patient Counseling

    Patient Counseling

    Risk of Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other VasospasmRelated Events, Arrhythmias, and Cerebrovascular Events 

    • Inform patients that Amerge may cause serious cardiovascular side effects such as myocardial infarction or stroke. 
    • Be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech and should ask for medical advice if any indicative signs or symptoms are observed. Apprise patients of the importance of this follow-up.

    Anaphylactic Reactions 

    • Inform patients that anaphylactic reactions have occurred in patients receiving Amerge. These reactions can be life-threatening or fatal.
    • In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens.

    Concomitant Use with Other Triptans or Ergot Medications 

    • Inform patients that use of Amerge within 24 hours of another triptan or an ergot-type medication (including dihydroergotamine or methysergide) is contraindicated.

    Serotonin Syndrome 

    • Caution patients about the risk of serotonin syndrome with the use of Amerge or other triptans, particularly during combined use with SSRIs, SNRIs, TCAs, and MAO inhibitors.

    Medication Overuse Headache 

    • Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (eg, by keeping a headache diary).

    Pregnancy 

    • Advise patients to notify their healthcare provider if they become pregnant during treatment or intend to become pregnant.

    Lactation 

    • Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.

    Ability to Perform Complex Tasks

    • Treatment with Amerge may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of Amerge. 

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