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 Drugs.com on Jul 22, 2024. Written by ASHP.

Introduction

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

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 for Naratriptan

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).

• Uncontrolled hypertension.

• Other serious underlying cardiovascular disease.

• Cerebrovascular syndromes (e.g., stroke syndrome, TIAs).

• Peripheral vascular disease or ischemic bowel disease.

• 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

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

Pregnancy

Category C.

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).

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

Naratriptan 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.

• Risk of serious cardiovascular or cerebrovascular events (e.g., MI, stroke) or other vasospastic reactions. Importance of seeking medical care if symptoms of such reactions (e.g., shortness of breath, weakness, slurring of speech, or tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck) occur 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.

• Overuse of drugs indicated for the management of acute migraine attacks may exacerbate headaches; importance of recording headache frequency and drug use to monitor effectiveness of treatment.

• 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, particularly 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.

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

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