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Pronunciation
(NAR a trip tan)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of acute migraine headache with or without aura
Pregnancy Risk Factor
C
Pregnancy Considerations
There are no adequate and well-controlled studies using naratriptan in pregnant women. Use only if potential benefit to the mother outweighs the potential risk to the fetus. A pregnancy registry has been established to monitor outcomes of women exposed to naratriptan during pregnancy (800-336-2176). In animal studies, administration was associated with embryolethality, fetal abnormalities, and pup mortality and growth retardation. Tremors were observed in the offspring of female rats when exposed to naratriptan late in gestation.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to naratriptan or any component of the formulation; cerebrovascular, peripheral vascular disease (ischemic bowel disease), ischemic heart disease (angina pectoris, history of myocardial infarction, or proven silent ischemia); or in patients with symptoms consistent with ischemic heart disease, coronary artery vasospasm, or Prinzmetal's angina; uncontrolled hypertension or patients who have received within 24 hours another 5-HT agonist (sumatriptan, zolmitriptan) or ergotamine-containing product; patients with known risk factors associated with coronary artery disease; patients with severe hepatic (Child-Pugh grade C) or renal disease (Clcr <15 mL/minute); do not administer naratriptan to patients with hemiplegic or basilar migraine
Warnings/Precautions
Concerns related to adverse effects:
• Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses.
• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration.
• Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension.
• Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns:
• Coronary artery disease: Should not be given to patients who have risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation “is satisfactory”, first dose should be given in the healthcare provider's office. Periodic evaluation of cardiovascular status should be done in all patients.
• Hepatic impairment: In patients with mild-to-moderate hepatic impairment, naratriptan clearance is reduced ~30% and the elimination half-life is increased ~40%; dosage adjustment required in this patient population. Use is contraindicated in patients with severe hepatic impairment (Child-Pugh grade C).
• Renal impairment: In patients with moderate renal impairment, naratriptan clearance is reduced ~50% and the elimination half-life is increased; dosage adjustment required in this patient population. Use is contraindicated in patients with severe renal impairment (Clcr <15 mL/minute).
Concurrent drug therapy issues:
• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce naratriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Other warnings/precautions:
• Appropriate use: Only indicated for the acute treatment of migraine; not indicated for migraine prophylaxis, or for the treatment of cluster headache, hemiplegic or basilar migraine. If a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered; rule out underlying neurologic disease in patients with atypical headache and in patients with no prior history of migraine. .
Adverse Reactions
1% to 10%:
Central nervous system: Pain/pressure (2% to 4%), malaise/fatigue (2%), dizziness (1% to 2%), drowsiness (1% to 2%), vertigo (1%)
Gastrointestinal: Nausea (4% to 5%), hyposalivation (1%), vomiting (1%)
Neuromuscular & skeletal: Paresthesia (1% to 2%)
Ocular: Photophobia (1%)
Miscellaneous: Ear/nose/throat infection (1%), pressure/tightness/heaviness sensations (1%), warm/cold temperature sensations (1%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Abnormal bilirubin tests, abnormal liver function tests, anaphylactoid reaction, anaphylaxis, anemia, bradycardia, cerebral infarction, colonic ischemia, coronary artery vasospasm, depression, dyspnea, ECG changes (atrial fibrillation, atrial flutter, premature ventricular contractions, PR prolongation, or QTc prolongation), eye hemorrhage, glycosuria, hallucinations, heart murmurs, hypercholesterolemia, hyperglycemia, hyper-/hypotension, hyperlipidemia, hypothyroidism, hypersensitivity reaction, ketonuria, MI, palpitation, panic, rash, seizure, serotonin syndrome, syncope, subarachnoid hemorrhage, thrombocytopenia, TIA, transient myocardial ischemia, ventricular fibrillation, ventricular tachycardia
Drug Interactions
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Storage
Store at 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
Pharmacodynamics/Kinetics
Onset of action: ~1-2 hours (Bomhof, 1999; Tfelt-Hansen, 2000)
Absorption: Well absorbed
Distribution: Vdss: 170 L
Protein binding, plasma: 28% to 31%
Metabolism: Hepatic via CYP
Bioavailability: ~70%
Half life, elimination: 6 hours; increased in renal impairment (moderate impairment; mean: 11 hours; range 7-20 hours); increased in hepatic impairment (moderate impairment: 8-16 hours)
Time to peak: 2-3 hours
Excretion: Urine (50% of total dose as unchanged drug; 30% of total dose as metabolites)
Dosage
Adults: Oral: 1-2.5 mg at the onset of headache; it is recommended to use the lowest possible dose to minimize adverse effects. If headache returns or does not fully resolve, the dose may be repeated after 4 hours; do not exceed 5 mg in 24 hours.
Elderly: Not recommended for use in the elderly
Dosing in renal impairment:
Mild-to-moderate renal impairment: Initial: 1 mg; do not exceed 2.5 mg in 24 hours
Severe renal impairment (Clcr <15 mL/minute): Use is contraindicated
Dosing in hepatic impairment:
Mild-to-moderate hepatic impairment (Child-Pugh grade A or B): Initial: 1 mg; do not exceed 2.5 mg in 24 hours
Severe hepatic impairment (Child-Pugh grade C): Use is contraindicated
Administration: Oral
Do not crush or chew tablet; swallow whole with water.
Patient Education
Do not crush or chew tablet; swallow whole with water. This drug is to be used to reduce your migraine, not to prevent or reduce the number of attacks. If headache returns or is not fully resolved, the dose may be repeated after 4 hours. If you have no relief with first dose, do not take a second dose without consulting prescriber. Do not exceed 5 mg in 24 hours. Do not take within 24 hours of any other migraine medication without first consulting prescriber. May cause dizziness, fatigue, drowsiness, nausea, or vomiting. Report immediately any chest pain, palpitations, or rapid heartbeat; tightness in throat or neck; or rash, itching, or hives.
Geriatric Considerations
Naratriptan was not studied in patients >65 years of age. Use in elderly patients is not recommended because of the presence of risk factors associated with adverse effects. These include the presence of coronary artery disease, decreased liver or renal function, and the risk of pronounced blood pressure increases.
Anesthesia and Critical Care Concerns/Other Considerations
Naratriptan should not be used in patients with a history of vasospastic disease, Prinzmetal's angina, or any critical vascular disease.
Cardiovascular Considerations
Coronary vasospasm has been associated with 5-HT1B/1D agonists. These agents are contraindicated in patients with documented ischemic of vasospastic coronary artery disease. Patients with risk factors for CAD may receive these agents, provided a cardiovascular evaluation yields satisfactory evidence that the patient is free of cardiovascular disease. In patients with risk factors for CAD, administration of the initial dose in a medically staffed/equipped facility (ie, physician's office) is recommended. In addition, ECG monitoring after the initial dose should be considered. Patients who acquire risk factors for CAD, or long-term users of agents from this class of medications, should undergo periodic cardiovascular evaluation.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness, dizziness, or fatigue; may rarely cause panic reactions or hallucinations
Mental Health: Effects on Psychiatric Treatment
SSRIs may cause hyper-reflexia, weakness, or lack of coordination when used with naratriptan; these combinations should be avoided
Nursing: Physical Assessment/Monitoring
Assess for clear diagnosis of migraine prior to beginning therapy. Cardiovascular status should be evaluated prior to initiating medication and periodically thereafter. Assess potential for interactions with ergot-containing drugs and SSRIs patient may be taking. Monitor closely, especially after the first dose. Monitor for drowsiness, nausea/vomiting, paresthesias, and hypertension. If no response to first dose, diagnosis of migraine should be re-evaluated.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 1 mg, 2.5 mg
Amerge®: 1 mg, 2.5 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Amerge)
1 mg (9): $290.00
2.5 mg (9): $292.00
Extemporaneously Prepared
A 0.5 mg/mL oral suspension may be made using tablets. Crush fifty 2.5 mg tablets and reduce to a fine powder. In small amounts, add 125 mL of Ora-Plus® and mix well after each addition. Transfer to a calibrated bottle, rinse mortar with vehicle, then add quantity of Ora-Sweet® or Ora-Sweet® SF sufficient to make 250 mL. Label "shake well" and "refrigerate". Stable 90 days refrigerated.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
Bomhof MK, Paz J, Legg N, et al, “Comparison of Rizatriptan 10 mg vs Naratriptan 2.5 mg in Migraine,” Eur Neurol 1999, 42(3):173-9.
Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.
Tfelt-Hansen P, de Vries P, Saxena PR, “Triptans in Migraine: A Comparative Review of Pharmacology, Pharmacokinetics and Efficacy,” Drugs, 2000, 60(6):1259-87.
International Brand Names
Lexi-Comp.com
Last full review/revision April 2011
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