Generic Name: naratriptan

Brand Names: Amerge

Uses

Vascular Headaches

Acute treatment of migraine attacks with or without aura.

Not recommended for management of hemiplegic or basilar migraine or for the prophylaxis of migraine.

Safety and efficacy not established for management of cluster headaches.

Dosage and Administration

Administration

Oral Administration

Administer orally with fluids.

Dosage

Available as naratriptan hydrochloride; dosage is expressed in terms of naratriptan.

Adults

Vascular Headaches

Migraine

Oral

1 or 2.5 mg as a single dose; individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 2.5-mg dose.

If headache recurs or only a partial response is achieved, may repeat dose once after 4 hours.

Following failure to respond to the first dose, reconsider diagnosis of migraine prior to administration of a second dose.

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 5 mg in any 24-hour period.

Safety of treating an average of >4 headaches per 30-day period not established.

Special Populations

Hepatic Impairment

Contraindicated in patients with severe hepatic impairment. In patients with mild or moderate hepatic impairment, reduce initial dosage; maximum dosage of 2.5 mg per 24-hour period is recommended.

Renal Impairment

Contraindicated in patients with severe renal impairment. In patients with mild or moderate renal impairment, reduce initial dosage; maximum dosage of 2.5 mg per 24-hour period is recommended.

Cautions

Contraindications

• Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).
• Coronary artery vasospasm (e.g., Prinzmetal variant angina).
• Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).
• Cerebrovascular syndromes (e.g., stroke syndrome, TIAs).
• Peripheral vascular ischemia (e.g., ischemic colitis).
• Severe hepatic impairment (e.g., Child-Pugh grade C).
• Severe renal impairment (e.g., Cl_cr ≤15 mL/minute).
• Hemiplegic or basilar migraine.
• Treatment within previous 24 hours with another 5-HT₁ receptor agonist or an ergot alkaloid. (See Specific Drugs under Interactions.)
• Known hypersensitivity to naratriptan or any ingredient in the formulation.

Warnings/Precautions

Warnings

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

Exclude other potentially serious neurologic disorders before administering naratriptan to patients not previously diagnosed with migraine or to those with atypical symptoms.

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.

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.

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.

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

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. If administration resumed and such signs or symptoms recur, ECG evaluation recommended.

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage, stroke, and other adverse cerebrovascular events, sometimes fatal, with use of 5-HT₁ receptor agonists.

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

Other Cardiovascular or Vasospastic Effects

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported. 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.

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.

Increases in mean pulmonary artery pressure and mean aortic pressure observed following naratriptan administration in patients with suspected CAD who were undergoing cardiac catheterization.

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). 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). (See Specific Drugs under Interactions.)

Sensitivity Reactions

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

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.

Specific Populations

Pregnancy

Category C. Pregnancy Registry at 800-336-2176.

Lactation

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

Pediatric Use

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

Geriatric Use

Use not recommended. Increased risk of CAD in this patient population. Possible increased risk of adverse effects in those with renal or hepatic impairment. More pronounced increases in BP possible in geriatric patients.

Hepatic Impairment

Use with caution. (See Hepatic Impairment under Dosage and Administration and also Special Populations under Pharmacokinetics.) Contraindicated in patients with severe hepatic impairment. (See Cautions.)

Renal Impairment

Use with caution. (See Renal Impairment under Dosage and Administration and also Special Populations under Pharmacokinetics.) Contraindicated in patients with severe renal impairment. (See Cautions.)

Common Adverse Effects

Paresthesia, nausea, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms (e.g., pain, pressure).

Interactions

Metabolized by a wide range of CYP isoenzymes.

Does not inhibit MAO enzymes and is a poor inhibitor of CYP isoenzymes; pharmacokinetic interactions with drugs metabolized by CYP or MAO unlikely.

Smoking

Potential pharmacokinetic interaction (increased naratriptan clearance).

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Well absorbed, with oral bioavailability of about 70%.

Peak plasma concentrations attained within 2–3 hours after oral administration. Absorption may be slower during a migraine attack, with peak plasma concentrations attained in 3–4 hours.

Food

Food does not affect pharmacokinetics of naratriptan.

Distribution

Extent

Distributed into milk in animals.

Plasma Protein Binding

28–31%.

Elimination

Metabolism

In vitro, metabolized by a wide range of CYP isoenzymes into inactive metabolites.

Elimination Route

Eliminated principally in urine, with approximately 50% of a dose excreted as unchanged drug and 30% as metabolites.

Half-life

6 hours.

Special Populations

In patients with moderate hepatic impairment (Child-Pugh grade A or B), clearance is decreased by approximately 30% .

In patients with moderate renal impairment (Cl_cr of 18–39 mL/minute), clearance is decreased by approximately 50%.

Stability

Storage

Oral

Tablets

20–25°C. Protect from heat and light.

Actions

• Binds with high affinity to 5-HT_1B and 5-HT_1D.
• Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, rizatriptan, sumatriptan, zolmitriptan).
• 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.

Advice to Patients

• Importance of informing clinicians of any atypical migraine symptoms.
• 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.
• Importance of informing clinician immediately if sudden and/or severe abdominal pain occurs.
• Importance of taking naratriptan exactly as prescribed.
• Importance of providing a copy of manufacturer’s patient information.
• 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).
• Importance of informing patients of risk of serotonin syndrome with concurrent use of naratriptan and an SSRI or SNRI. Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions June 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.