Trade name

Amerge® (naratriptan hydrochloride) tablets, for oral use

Dosage forms and strengths

Tablet: 1 mg, 2.5 mg, and 5 mg

Amerge (generic name: naratriptan) is a prescription medication used to treat migraine headaches. Amerge works by narrowing blood vessels around the brain, which helps to relieve pain and other symptoms associated with migraines. Amerge is usually taken as needed for migraine relief, but it can also be used on a daily basis to prevent migraines from occurring. Possible side effects of Amerge include dizziness, sleepiness, dry mouth, and nausea. This medication should not be used if you are allergic to naratriptan or any other ingredient in Amerge. Before taking Amerge, tell your doctor about all other medications you are taking (including over-the-counter medications), as well as any medical conditions you have. Amerge is not recommended for use during pregnancy. This medication passes into breast milk and could have harmful effects on a nursing baby. Amerge should not be used by anyone under the age of 18. For more information on this medication, please consult with your health care provider.

Amerge

Pharmacokinetics

Naratriptan is rapidly and well absorbed following oral administration, with maximum plasma concentrations achieved within 2 hours. The bioavailability of naratriptan is about 40%. Naratriptan is extensively metabolized, with only 5% of the dose recovered as unchanged drug in the urine. The primary metabolites are formed by monoamine oxidase-mediatedfirst-pass metabolism and are present in plasma at much lower concentrations than the parent compound. Naratriptan has a volume of distribution of about 3 L/kg and is about 95% bound to plasma proteins. Plasma clearance of naratriptan is about 1.3 L/hr/kg. The elimination half-life of naratriptan is about 3 hours.

Indications and Usage

Amerge is indicated for the acute treatment of migraines with or without aura in adults. Amerge is not intended for prophylactic therapy.

Pediatric use

Safety and effectiveness of Amerge in pediatric patients have not been established.

Geriatric use

Clinical studies of Amerge did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Contraindications

Amerge is contraindicated in patients with:

– Ischemic coronary artery disease or other significant underlying cardiovascular disease (see WARNINGS)

– History of stroke or transient ischemic attack (see WARNINGS)

– Peripheral vascular disease or raynaud’s phenomenon (see WARNINGS)

– Hepatic impairment (see CLINICAL PHARMACOLOGY and WARNINGS)

– Known hypersensitivity to naratriptan or any of the excipients in Amerge (see WARNINGS)

Warnings

Ischemic coronary artery disease and other significant underlying cardiovascular disease

Naratriptan is contraindicated in patients with ischemic coronary artery disease or other significant underlying cardiovascular disease (see CONTRAINDICATIONS). Naratriptan should not be given to patients with uncontrolled hypertension. In clinical trials, naratriptan was associated with an increase in blood pressure that was dose-related and usually not clinically significant. However, rare reports of hypertensive episodes were received during postmarketing surveillance. Some of these reports described patients who had no history of hypertension. If a patient treated with naratriptan has hypertension, treatment should be discontinued and the patient should be evaluated.

Side Effects

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

– Ischemic coronary artery disease and other significant underlying cardiovascular disease (see WARNINGS)

– History of stroke or transient ischemic attack (see WARNINGS)

– Peripheral vascular disease or raynaud’s phenomenon (see WARNINGS)

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Amerge was evaluated for safety in two multicenter, randomized, double-blind, placebo-controlled trials in 1,177 adult migraineurs. These trials enrolled patients with a history of migraines (with or without aura) for at least one year, who had experienced at least four migraines in the three months prior to screening, and who were experiencing two to eight moderate to severe migraines per month during the run-in phase. In both studies, the most frequently observed adverse reactions (> 5%) in Amerge-treated patients that were more common than in placebo-treated patients are listed below.

Table 2: Adverse Reactions Reported by ≥ 2% of Patients Treated With Amerge and More Common Than Placebo in Two Multicenter, Randomized, Double-Blind, Placebo-Controlled Trials of Acute Treatment of Migraine

Body System/Adverse Reaction Percent of Patients Reporting Reaction Amerge Placebo (n=1,177) (n=592) Cardiovascular Palpitations 1.0% 0.8% Digestive Nausea 10.2% 3.2% Vomiting 5.9% 2.0% Diarrhea 2.6% 1.7% Abdominal pain 2.3% 1.5% Dyspepsia 2.1% 1.4% Dry mouth 2.0% 1.0% Metabolic and Nutritional Hypercholesterolemia 4.1* 3.6 Hypokalemia 3.7* 3 Nervous Somnolence 7.3% 2.6% Dizziness 5.8% 3.7% Paresthesia 4.9% 2.2% Muscle weakness 4.0* 3.2 Psychiatric Anxiety 3.4% 1.8% Respiratory Pharyngitis 3.5* 2 Sinusitis 2.5* 1 Skin and Appendages Sweating 5.3* 3

Dosage

The recommended starting dose of Amerge is 1 mg (2 tablets) as soon as possible after the onset of a migraine. If the headache improves but then returns, the dose may be repeated once after 2 hours, provided that a total daily dose of 2 mg (4 tablets) has not been exceeded. The maximum recommended frequency of dosing in any 24-hour period is two doses. In clinical trials, efficacy was demonstrated when naratriptan was used at the first signs and symptoms of a migraine. Amerge may be taken with or without food.

Overdose

Symptoms

The most common symptom of an overdose is drowsiness. Other reported symptoms include: tachycardia, bradycardia, hypertension, hypotension, dyspnea, and chest pain. There have been reports of serotonin syndrome in association with use of 5-HT1 agonists.

Treatment

In case of overdose, discontinue Amerge immediately and initiate supportive and symptomatic treatment as appropriate. Monitor blood pressure and heart rate continuously and treat appropriately if necessary. If hypotension or hypertension occurs , correct these abnormalities by giving vasopressors or antihypertensives according to the patient’s clinical status. Consider the possibility of multi-drug overdose. Administer activated charcoal orally if the patient presents within 1 hour of ingestion. Consider gastric lavage with a large bore nasogastric tube if the patient presents more than 1 hour after ingestion and if there is any reason to believe that a significant amount of drug remains in the gastrointestinal tract.

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) .

Dispensing

Amerge is supplied as a 2.5 mg tablets for oral administration. Each tablet contains the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80 and titanium dioxide. Amerge 2.5 mg tablet also contains FD&C Blue No. 2 Aluminum Lake as a color additive.

How Supplied / Storage and Handling

Amerge® (naratriptan HCl) tablets are white to off-white, flat-faced, beveled edge, modified oval shaped tablets debossed with a partial scoreline on one side and plain on the other side.

Bottles of 6 Tablets NDC 0228-2505-06

Bottles of 12 Tablets NDC 0228-2505-12

Blister packages of 2 x 6 Tablets NDC 0228-2505-26 Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) . Keep out of reach of children. Dispense in a tight, light resistant container as defined in the USP/NF. Amerge is a registered trademark of GlaxoSmithKline.