Naratriptan

Pronunciation: NAHR-ah-trip-tan
Class: Serotonin 5-HT 1 receptor agonist

Trade Names

Amerge
- Tablets 1 mg (as hydrochloride)
- Tablets 2.5 mg (as hydrochloride)

Pharmacology

Binds to serotonin (5-HT) 1 B and 1 D receptors in intracranial arteries leading to vasoconstriction and subsequent relief of migraine headache.

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

Pharmacokinetics

Absorption

Bioavailability of naratriptan is 70%, AUC is 98 mcg/L•h, T max is 2 to 3 h, T max during migraine attack is 3 to 4 h, and C max is 12.6 mcg/L.

Distribution

Naratriptan Vd is 170 L and protein binding is 28% to 31%.

Metabolism

Naratriptan is metabolized in the liver by CYP-450 enzymes to inactive metabolites.

Elimination

Naratriptan is eliminated in urine, 50% unchanged and 30% as metabolites (inactive). The t ½ is 6 h, systemic Cl is 6.6 mL/min/kg, and renal Cl is 220 mL/min.

Special Populations

Renal Function Impairment

Naratriptan Cl is reduced 50% with moderate impairment (CrCl 18 to 39 mL/min). This resulted in an increase of t ½ from 6 to 11 h, and mean C max was increased about 40%.

Hepatic Function Impairment

Naratriptan Cl is decreased 30%, which resulted in about a 40% increase in the t ½ from 8 to 16 h.

Gender

C max is 50% higher in women.

Indications and Usage

Treatment of acute migraine attacks with or without aura.

Contraindications

Patients with history, signs, or symptoms of ischemic heart disease (eg, angina, including Prinzmetal variant, MI, silent myocardial ischemia), cerebrovascular or peripheral vascular syndromes, uncontrolled hypertension, severe renal or hepatic insufficiency, patients with hemiplegic or basilar migraine, or hypersensitivity to any component of the product. Naratriptan is contraindicated within 24 h of use with other serotonin agonists, ergotamine compounds, or methysergide.

Dosage and Administration

Adults

PO 1 or 2.5 mg with onset of migraine headache. Dose is individualized based on response and adverse reactions. The dose may be repeated once after 4 h if partial response or if the headache returns. The max daily dose is 5 mg in 24 h.

General Advice

  • Administer without regard to meals.
  • Do not administer within 24-h of treatment with another 5-HT 1 agonist or ergot-containing drug.
  • Do not administer more than 5 mg per 24-h period in patient with healthy renal function or more than 2.5 mg per 24-h period in patient with mild to moderate renal function impairment or mild to moderate hepatic function impairment.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F).

Drug Interactions

5-HT 1 agonists (eg, sumatriptan)

Increased risk of vasospastic reactions; therefore, coadministration of two 5-HT 1 agonists within 24 h of each other is contraindicated.

Ergot-containing drugs

May cause additive, prolonged vasospasm.

Selective serotonin reuptake inhibitors (eg, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

Weakness, hyperreflexia, and incoordination have been rarely reported.

Sibutramine

Serotonin syndrome, including CNS irritability, motor weakness, shivering, myoclonus, and altered consciousness may occur.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina, MI (postmarketing).

CNS

Dizziness, drowsiness, malaise/fatigue, paresthesia (2%); vertigo (at least 1%); cerebral vascular accident, including transient ischemic attack, subarachnoid hemorrhage, and cerebral infarction (postmarketing).

EENT

Ear, nose, and throat infections, photophobia (at least 1%).

GI

Nausea (5%); hyposalivation, vomiting (at least 1%); colonic ischemia (postmarketing).

Hypersensitivity

Hypersensitivity, including anaphylaxis/anaphylactoid reactions (postmarketing).

Respiratory

Dyspnea (postmarketing).

Miscellaneous

Atypical sensation (4%); pain and pressure in neck and throat (2%); warm/cold temperature sensation, sensations of pressure, tightness, and heaviness (at least 1%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Not recommended.

Hypersensitivity

Hypersensitivity reactions (including anaphylaxis and anaphylactoid reactions) may occur.

Cardiac

May cause coronary vasospasm in patients with coronary artery disease (CAD).

Cerebrovascular events

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with 5-HT 1 agonists.

Hypertensive crisis

Elevation in BP, including hypertensive crisis, have been reported with administration of 5-HT 1 agonists.

Overdosage

Symptoms

Hypertension, cardiac ischemia, lightheadedness, neck tension, loss of coordination.

Patient Information

  • Advise patient to read the patient information leaflet before starting therapy and again with each refill.
  • Explain that drug is to be used only during migraine and does not prevent or reduce the number of attacks. Emphasize that drug is used only to treat actual migraine attack and should not be used to prevent migraine headaches or treat headaches caused by other conditions.
  • Advise patient that drug is to be taken as soon as symptoms of migraine appear. A second dose may be taken if symptoms return, but no sooner than 4 h following the first dose. For a given attack, if there is no response to the first tablet, do not take a second tablet without first consulting with health care provider. Caution patient not to take more than 2 doses in any 24-h period.
  • Advise patient that safety of treating more than 4 headaches in a 30-day period has not been established and to inform health care provider if headaches are occurring more frequently.
  • Advise patient to immediately notify health care provider if any of the following occur after taking a dose of naratriptan: severe chest pain or chest pain that does not go away; sudden and/or severe stomach pain; shortness of breath; wheezing; swelling of eyelids, face, or lips.
  • Advise patient that if tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw occur when using naratriptan, to discuss these symptoms with health care provider before using again.
  • Advise patient to notify health care provider if feelings of tingling, heat, flushing, tiredness, dizziness, heaviness, or pressure occur after treatment.
  • Advise patient that drug may cause fatigue or dizziness and to use caution while driving or performing other activities requiring mental alertness.
  • Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
  • Instruct patient to continue taking prescribed migraine prophylactic medications daily as directed.
  • Advise patient not currently taking migraine prophylactic drugs to discuss the use of such drugs with health care provider.

Copyright © 2009 Wolters Kluwer Health.

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