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Naratriptan (Monograph)

Brand name: Amerge
Drug class: Selective Serotonin Agonists
- Antimigraine Agents
- Selective Vascular Serotonin Type 1-Like Receptor Agonists
- 5-HT1 Agonists
VA class: CN105
Chemical name: N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide monohydrochloride
Molecular formula: C17H25N3O2S•HCl
CAS number: 143388-64-1

Medically reviewed by on Jul 21, 2023. Written by ASHP.


Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).

Uses for Naratriptan

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.

Naratriptan Dosage and Administration


Oral Administration

Administer orally with fluids.


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


Vascular Headaches

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


Vascular Headaches

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 for Naratriptan



Careful Diagnosis of Migraine

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

If a given migraine attack fails to respond to the first dose of naratriptan, reconsider diagnosis before administering a second dose.

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

Cardiac Effects

Possible myocardial ischemia and/or infarction and coronary vasospasm, even in patients without a history of CAD. Contraindicated in patients with ischemic or vasospastic heart disease.

Possible fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation). Discontinue if such disturbances occur.

Tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently but usually are noncardiac in origin. Manufacturer states that 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 is resumed and such signs or symptoms recur, ECG evaluation recommended.

Patients at Risk for CAD

Perform cardiovascular evaluation prior to initiating therapy in patients with multiple cardiovascular risk factors (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of CAD) who have not previously received 5-HT1 receptor agonist therapy.

If evaluation provides evidence of CAD or coronary vasospasm, do not administer the drug.

If results of evaluation are satisfactory, consider administering the initial dose in a medically supervised setting followed immediately by an ECG.

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

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage and stroke, sometimes fatal. (See Careful Diagnosis of Migraine under Cautions.) Discontinue therapy if a cerebrovascular event occurs.

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

Other Vasospastic Effects

Possible noncoronary vasospastic reactions (e.g., peripheral vascular ischemia, GI ischemia and infarction with abdominal pain and bloody diarrhea, splenic infarction, Raynaud’s syndrome); transient or permanent blindness and partial vision loss reported in patients receiving 5-HT1 receptor agonists.

If signs or symptoms suggestive of vasospasm occur following administration, evaluate patient to rule out vasospastic reaction before administering additional doses.

Hypertensive Effects

Substantial increases in BP, including hypertensive crisis with acute impairment of organ systems, 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 arterial 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 in patients receiving 5-HT1 receptor agonists, particularly in those receiving SSRIs or SNRIs concomitantly. (See Specific Drugs under Interactions.) Also may occur in patients receiving MAO inhibitors or tricyclic antidepressants concomitantly.

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).

If manifestations of serotonin syndrome occur, discontinue naratriptan and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.

Medication Overuse Headache

Overuse of drugs indicated for management of acute migraine attacks (e.g., use of 5-HT1 receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for ≥10 days per month) may result in migraine-like daily headaches or a marked increase in frequency of migraine attacks.

Detoxification, including withdrawal of overused drugs; treatment of withdrawal symptoms (e.g., transient worsening of headaches); and consideration of prophylactic migraine therapy may be necessary.

Sensitivity Reactions

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

Specific Populations


Category C.


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).

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.


Potential pharmacokinetic interaction (increased naratriptan clearance).

Specific Drugs




Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)

Potentially life-threatening serotonin syndrome

Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated

Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide [no longer commercially available in the US])

Possible additive vasospastic effects

Use within 24 hours contraindicated

5-HT1 receptor agonists

Possible additive vasospastic effects

Use within 24 hours contraindicated

Oral contraceptives

Possible slightly increased plasma concentrations of naratriptan

Naratriptan Pharmacokinetics



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 does not affect pharmacokinetics of naratriptan.



Distributed into milk in animals.

Plasma Protein Binding




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.


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 (Clcr of 18–39 mL/minute), clearance is decreased by approximately 50%.





20–25°C. Protect from heat and light.


Advice to Patients


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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Naratriptan Hydrochloride


Dosage Forms


Brand Names



Tablets, film-coated

1 mg (of naratriptan)*



Naratriptan Hydrochloride Tablets

2.5 mg (of naratriptan)*



Naratriptan Hydrochloride Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 31, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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