Amerge

Included as part of the PRECAUTIONS section.

Amerge is a prescription medicine used to treat migraine headaches in adults. Amerge belongs to a group of drugs called 5-HT agonists or "triptans".  It is believed to work by causing dilated blood vessels in the brain to narrow.

Amerge comes in tablet form and is taken by mouth as soon as a migraine starts.

Common side effects of Amerge include dizziness, feeling hot or cold, and light sensitivity.

For some people, the first dose of Amerge should be taken in their doctor's office. Ask your doctor if you should take your first dose in a medical setting.

Amerge comes as a tablet to be taken by mouth as soon as possible once a migraine starts.

Amerge tablets should be swallowed whole with water or other liquids. Do not chew or crush Amerge  tablets. This medication can be taken with or without food.

Your doctor may instruct you to take a second dose of Amerge if your migraine does not go away after the first dose. Wait at least four hours after the first dose before taking a second dose of Amerge. Do not take more than a total of 5 mg of Amerge in a 24‑hour period.

Amerge is not meant to be taken on a daily basis. Take Amerge only when you have a migraine.

If you take too much Amerge, call your healthcare provider or go to the nearest hospital emergency room right away.

Since naratriptan is used as needed, it does not have a daily dosing schedule. Call your doctor if your symptoms do not improve after using naratriptan.

Do not take naratriptan within 24 hours before or after using another migraine headache medicine, including:

• medicines like naratriptan--almotriptan, eletriptan, frovatriptan, rizatriptan, sumatriptan, zolmitriptan, and others; or

• ergot medicine--dihydroergotamine, ergotamine, ergonovine, methylergonovine.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

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

Category C.1

Naratriptan and/or its metabolites are distributed into milk in rats.1 Caution advised if naratriptan is used.1

Safety and efficacy not established in children <18 years of age.1

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

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.)

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

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

• 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.)

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Using too much naratriptan may increase the chance of side effects.

Do not use naratriptan for a headache that is different from your usual migraines. Talk to your doctor about what to do for regular headaches.

To relieve your migraine as soon as possible, take naratriptan with water or other liquids as soon as the headache pain begins. Even if you get warning signals of a coming migraine (an aura), you should wait until the headache pain starts before using naratriptan.

Ask your doctor ahead of time about any other medicine you may take if naratriptan does not work. After you take the other medicine, check with your doctor as soon as possible. Headaches that are not relieved by naratriptan are sometimes caused by conditions that need other treatment.

If you feel much better after a dose of naratriptan, but your headache comes back or gets worse after a while, you may take one additional dose of this medicine 4 hours after the first dose. Do not use more than 5 milligrams in any 24-hour period.

This medicine comes with a patient information leaflet. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For migraine headaches:
    • Adults—1 or 2.5 milligrams (mg) taken as a single dose. If the migraine comes back after being relieved, another dose may be taken 4 hours after the last dose. Do not take more than 5 mg in any 24-hour period.
    • Children—Use and dose must be determined by your doctor.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling sleepy.
• Feeling tired or weak.
• Flushing.
• Feeling of warmth.
• Upset stomach.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Amerge is contraindicated in patients with:

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. Some of these reactions occurred in patients without known CAD. 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 (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving Amerge. If there is evidence of CAD or coronary artery vasospasm, Amerge is contraindicated. 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 administration of Amerge. 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. However, 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. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., 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. Since visual disorders 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 (e.g., 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 [see Drug Interactions (7.3)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). 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

There have been reports of anaphylaxis and hypersensitivity reactions, including angioedema, in patients receiving Amerge. Such 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.

Amerge contains naratriptan hydrochloride, a selective 5-HT1B/1D receptor agonist. Naratriptan hydrochloride is chemically designated as N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide monohydrochloride, and it has the following structure:

The empirical formula is C17H25N3O2S•HCl, representing a molecular weight of 371.93. Naratriptan hydrochloride is a white to pale yellow powder that is readily soluble in water.

Each Amerge tablet for oral administration contains 1.11 or 2.78 mg of naratriptan hydrochloride, equivalent to 1 or 2.5 mg of naratriptan, respectively. Each tablet also contains the inactive ingredients croscarmellose sodium; hypromellose; lactose; magnesium stearate; microcrystalline cellulose; triacetin; and titanium dioxide, iron oxide yellow (2.5-mg tablet only), and indigo carmine aluminum lake (FD&C Blue No. 2) (2.5-mg tablet only) for coloring.

Amerge tablets containing 1 mg and 2.5 mg of naratriptan (base) as the hydrochloride salt.

Amerge tablets, 1 mg, are white, D-shaped, film-coated tablets debossed with “GX CE3” on one side in blister packs of 9 tablets (NDC 0173-0561-00).

Amerge tablets, 2.5 mg, are green, D-shaped, film-coated tablets debossed with “GX CE5” on one side in blister packs of 9 tablets (NDC 0173-0562-00).

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

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

You should not take this medication if you are allergic to naratriptan, if you have any history of heart disease, or if you have coronary heart disease, angina, blood circulation problems, lack of blood supply to the heart, uncontrolled high blood pressure, severe liver or kidney disease, ischemic bowel disease, a history of a heart attack or stroke, or if your headache seems to be different from your usual migraine headaches.

Do not take naratriptan within 24 hours before or after using another migraine headache medicine, including almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), rizatriptan (Maxalt), sumatriptan (Imitrex, Treximet), zolmitriptan (Zomig), or ergot medicine such as ergotamine (Ergomar, Cafergot, Migergot), dihydroergotamine (D.H.E. 45, Migranal), or methylergonovine (Methergine).

Before taking naratriptan, tell your doctor if you have liver or kidney disease, high blood pressure, a heart rhythm disorder, or coronary heart disease (or risk factors such as diabetes, menopause, smoking, being overweight, having high cholesterol, having a family history of coronary artery disease, being older than 40 and a man, or being a woman who has had a hysterectomy).

Also tell your doctor if you are also taking an antidepressant such as citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), or venlafaxine (Effexor).

Naratriptan will only treat a headache that has already begun. It will not prevent headaches or reduce the number of attacks.

If your headache does not go away after taking a naratriptan tablet, or if the headache goes away and then comes back, call your doctor before taking a second tablet. You must wait at least four (4) hours after you have taken the first tablet before you take the second tablet. Do not take more than two (2) naratriptan tablets in 24 hours.

If your symptoms have not improved after taking 2 tablets in 24 hours, contact your doctor before taking any more tablets.

LactMed Record Number

576

Last Revision Date

20130907

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