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Naratriptan: Drug information

Naratriptan: Drug information
(For additional information see "Naratriptan: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Amerge [DSC]
Brand Names: Canada
  • Amerge;
  • SANDOZ Naratriptan;
  • TEVA-Naratriptan
Pharmacologic Category
  • Antimigraine Agent;
  • Serotonin 5-HT1B, 1D Receptor Agonist
Dosing: Adult

Note: Do not use within 24 hours of an ergotamine preparation or a different triptan. Limit use to <10 days per month to avoid medication-overuse headache (AHS [Ailani 2021]).

Menstrual migraine prevention

Menstrual migraine prevention (off-label use): Oral: 1 mg twice daily beginning 2 to 3 days prior to expected onset of symptoms; continue for a total of 5 to 6 days (Mannix 2007; Newman 2001).

Migraine, moderate to severe, acute treatment

Migraine, moderate to severe, acute treatment:

Note: Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment. When attack is complicated by severe nausea or vomiting, a nonoral medication may be more effective (AHS [Ailani 2021]).

Oral: 2.5 mg as a single dose; if symptoms persist or return, may repeat dose after ≥4 hours. Maximum: 2.5 mg/dose; 5 mg per 24 hours (Mathew 1997; manufacturer’s labeling).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Mild to moderate renal impairment: Initial: 1 mg; maximum dose: 2.5 mg per 24 hours.

Severe renal impairment (CrCl <15 mL/minute): Use is contraindicated.

Dosing: Hepatic Impairment: Adult

Mild to moderate hepatic impairment (Child-Pugh grade A or B): Initial: 1 mg; maximum dose: 2.5 mg per 24 hours.

Severe hepatic impairment (Child-Pugh grade C): Use is contraindicated.

Dosing: Older Adult

Refer to adult dosing. Dosing should generally start at the lower end of the dosing range due to possible increased incidence of hepatic, renal, and cardiac impairment.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Amerge: 1 mg [DSC], 2.5 mg [DSC]

Generic: 1 mg, 2.5 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Amerge: 1 mg [DSC]

Amerge: 2.5 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Generic: 1 mg, 2.5 mg

Administration: Adult

Oral: Administer orally as soon as symptoms appear; may take with or without food. Do not crush or chew tablet; swallow whole with water.

Use: Labeled Indications

Migraine, moderate to severe, acute treatment: Acute treatment of migraine attacks with or without aura in adults.

Use: Off-Label: Adult

Menstrual migraine prevention

Medication Safety Issues
Sound-alike/look-alike issues:

Amerge may be confused with Altace, Amaryl

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Central nervous system: Pain (4%), fatigue (2%), dizziness (1% to 2%), drowsiness (1% to 2%), paresthesia (1% to 2%), hot and cold flashes (1%), sensation of pressure (1%; chest/neck/throat/jaw), vertigo (1%)

Gastrointestinal: Nausea (4% to 5%), vomiting (1%), xerostomia (1%)

Neuromuscular & skeletal: Neck pain (2%)

Ophthalmic: Photophobia (1%)

Respiratory: Constriction of the pharynx (2%), ENT infection (1%)

<1%, postmarketing, and/or case reports (limited to important or life-threatening): Abnormal bilirubin levels, abnormal hepatic function tests, anaphylactoid reaction, anaphylaxis, anemia, angina pectoris, angioedema, bradycardia, cerebral infarction, colonic ischemia, coronary artery vasospasm, depression, dyspnea, ECG changes (atrial fibrillation, atrial flutter, premature ventricular contractions, PR prolongation, or QTc prolongation), glycosuria, hallucination, heart murmur, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypersensitivity reaction (some cases severe, including circulatory collapse), hypertension, hypotension, hypothyroidism, ischemic heart disease, ketonuria, myocardial infarction, palpitations, panic, seizure, serotonin syndrome, skin rash, subarachnoid hemorrhage, subconjunctival hemorrhage, syncope, thrombocytopenia, transient ischemic attacks, ventricular fibrillation, ventricular tachycardia

Contraindications

Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction [MI], or documented silent ischemia); coronary artery vasospasm, including Prinzmetal's angina; Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders; history of stroke, transient ischemic attack (TIA), or history of hemiplegic migraine or migraine with brainstem aura; peripheral vascular disease; ischemic bowel disease; uncontrolled hypertension; recent use (within 24 hours) of another 5-HT1 agonist, ergotamine-containing medication, or ergot-type medication (eg, dihydroergotamine or methysergide); severe renal impairment (CrCl <15 mL/minute) or severe hepatic impairment; hypersensitivity to naratriptan or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Severe hypertension, cardiac arrhythmias (especially tachycardias); valvular heart disease, significant underlying cardiovascular disease (eg, congenital heart disease, atherosclerotic disease); management of ophthalmoplegic migraine

Documentation of allergenic cross-reactivity for triptans is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic reactions: Anaphylaxis and hypersensitivity reactions (including angioedema) have occurred; may be life-threatening or fatal. Use is contraindicated in patients with known hypersensitivity to naratriptan.

• Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration; some events have occurred within a few hours of administration. Discontinue if these events occur. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease (CAD) or Prinzmetal's angina before receiving additional doses; if dosing is resumed and similar symptoms recur, monitor with ECG. Use is contraindicated in patients with ischemic or vasospastic CAD and Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke (some fatal) have been reported with 5-HT1 agonist administration. Use is contraindicated in patients with a history of stroke or transient ischemic attack.

• CNS depression: May cause CNS depression, such as dizziness, weakness, or drowsiness, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients with and without a history of hypertension. Monitor blood pressure; use is contraindicated in patients with uncontrolled hypertension.

• Headaches: Acute migraine agents (eg, triptans, opioids, ergotamine, or a combination of the agents) used for 10 or more days per month may lead to worsening of headaches (medication overuse headache); withdrawal treatment may be necessary in the setting of overuse.

• Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia, gastrointestinal vascular ischemia and infarction, splenic infarction, and Raynaud syndrome have been reported with 5-HT1 agonist administration.

• Visual effects: Partial vision loss and blindness (transient and permanent) have been reported with use of 5-HT1 agonists; a causal relationship between these events and 5-HT1 agonist administration has not been clearly determined.

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. Use is contraindicated if there is evidence of CAD or coronary artery vasospasm. 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 health care provider's office (consider ECG monitoring). Periodic evaluation of cardiovascular status should be done in all patients.

• Hepatic impairment: Use is contraindicated in patients with severe hepatic impairment (Child-Pugh grade C).

• Renal impairment: Use is contraindicated in patients with severe renal impairment (CrCl <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. If concomitant administration with SSRIs is warranted, monitor closely, especially at initiation and with dose increases. Discontinue naratriptan if serotonin syndrome is suspected.

Special populations:

• Older adult: Blood pressure increases may be more pronounced in the elderly.

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.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Bromocriptine: May enhance the adverse/toxic effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Management: Consider alternatives to this combination when possible. If combined, monitor for increased bromocriptine and triptan toxicities. Risk D: Consider therapy modification

Droxidopa: Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the hypertensive effect of Droxidopa. Risk C: Monitor therapy

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Monoamine Oxidase Inhibitors: Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase the serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid combination

Serotonergic Agents (High Risk): Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

SUMAtriptan: Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the adverse/toxic effect of SUMAtriptan. Risk X: Avoid combination

Pregnancy Considerations

Pregnancy outcome information for naratriptan is available from a pregnancy registry sponsored by GlaxoSmithKline. As of September 2012, data were available for 57 infants/fetuses exposed to naratriptan, and seven exposed to both naratriptan and sumatriptan. Following naratriptan exposure, there was one infant born with a birth defect; this infant was also exposed to sumatriptan during the first trimester of pregnancy. The pregnancy registry was closed to enrollment in January 2012. Additional information related to the use of naratriptan in pregnancy is limited (Källén 2011; Nezvalová-Henriksen 2010; Nezvalová-Henriksen 2012). Until additional information is available, other agents are preferred for the initial treatment of migraine in pregnancy (Da Silva 2012; MacGregor 2012; Williams 2012).

Breastfeeding Considerations

It is not known if naratriptan is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Headache severity, blood pressure, signs/symptoms suggestive of angina; perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD), monitor ECG with first dose in patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation and consider periodic cardiovascular evaluation in such patients if they are intermittent long-term users; signs/symptoms of serotonin syndrome and hypersensitivity reactions.

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

Pharmacokinetics

Onset of action: ~1 to 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 to 20 hours); Increased in hepatic impairment (moderate impairment: 8 to 16 hours)

Time to peak: 2 to 3 hours

Excretion: Urine (50% of total dose as unchanged drug; 30% of total dose as metabolites)

Pharmacokinetics: Additional Considerations

Altered kidney function: Naratriptan clearance is reduced 50% with moderate impairment (CrCl 18 to 39 mL/minute); mean Cmax increased ~40%.

Hepatic function impairment: Naratriptan clearance is decreased 30% in patients with moderate impairment (Child-Pugh class A or B).

Older adult: Clearance is decreased ~26% in healthy elderly subjects (65 to 77 years) compared with younger patients.

Sex: Cmax is 50% higher in women.

Pricing: US

Tablets (Naratriptan HCl Oral)

1 mg (per each): $25.00 - $29.49

2.5 mg (per each): $25.00 - $29.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Amerge (JP);
  • Formigran (DE);
  • Migtal (CL);
  • Nacralid (RO);
  • Naramig (AE, AR, AU, BE, BG, BH, BR, CH, CL, CO, CY, CZ, DE, EC, EE, EG, ES, FI, FR, GB, GR, HU, IL, IQ, IR, JO, KR, KW, LB, LT, LU, LY, MX, NL, NO, NZ, OM, PE, PL, PT, QA, RU, SA, SE, SG, SI, SY, TH, TR, UY, YE, ZA);
  • Naratano (BR);
  • Naratrex (IN);
  • Naraverg (IE, MT);
  • Narcef (BR);
  • Naredrix (EG);
  • Nartan (CL);
  • Royamigran (EG);
  • Zomigren (CL)


For country code abbreviations (show table)
  1. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. doi:10.1111/head.14153 [PubMed 34160823]
  2. Amerge (naratriptan) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; October 2020.
  3. Amerge (naratriptan) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; November 2016.
  4. 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. [PubMed 10529545]
  5. Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20. [PubMed 15784664]
  6. Källén B, Nilsson E, and Otterblad Olausson P, "Delivery Outcome After Maternal Use of Drugs for Migraine: A Register Study in Sweden," Drug Saf, 2011, 34(8):691-703. [PubMed 21751829]
  7. MacGregor EA, "Headache in Pregnancy," Neurol Clin, 2012, 30(3):835-66. [PubMed 22840792]
  8. Mannix LK, Savani N, Landy S, et al. Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies. Headache. 2007;47(7):1037-1049. [PubMed 17635595]
  9. Mathew NT, Asgharnejad M, Peykamian M, Laurenza A. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. The Naratriptan S2WA3003 Study Group. Neurology. 1997;49(6):1485-1490. doi:10.1212/wnl.49.6.1485 [PubMed 9409334]
  10. Newman L, Mannix LK, Landy S, et al. Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study. Headache. 2001;41(3):248-256. [PubMed 11264684]
  11. Nezvalová-Henriksen K, Spigset O, and Nordeng HM, "Errata in 'Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From the Norwegian Mother and Child Cohort Study,'" Headache, 2012, 52(8):1319-20. [PubMed 22946832]
  12. Nezvalová-Henriksen K, Spigset O, and Nordeng H, "Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From the Norwegian Mother and Child Cohort Study," Headache, 2010, 50(4):563-75. [PubMed 20132339]
  13. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society [published correction appears in Neurology. 2013;80(9):871]. Neurology. 2012;78(17):1337-1345. doi: 10.1212/WNL.0b013e3182535d20. [PubMed 22529202]
  14. 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. [PubMed 11152011]
  15. Williams SH and Kehr HA, "An Update in the Treatment of Neurologic Disorders During Pregnancy-Focus on Migraines and Seizures," J Pharm Pract, 2012, 25(3):341-51. [PubMed 22550159]
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