Naratriptan

Naratriptan binds with high affinity to human cloned 5-HT 1B/1D receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (including substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system.

• Naratriptan tablets are indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: Use only if a clear diagnosis of migraine has been established.ICD-10: G43.909

• Naratriptan tablets are contraindicated in patients with: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina [see Warnings and Precautions (5.1) ] Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2) ] History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because such patients are at a higher risk of stroke [see Warnings and Precautions (5.4) ] Peripheral vascular disease [see Warnings and Precautions (5.5) ] Ischemic bowel disease [see Warnings and Precautions (5.5) ] Uncontrolled hypertension [see Warnings and Precautions (5.8) ] Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions ( 7.1 , 7.2 )] Hypersensitivity to naratriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9) ] Severe renal or hepatic impairment [see Use in Specific Populations ( 8.6 , 8.7 ), Cl…contraindicated

Recommended dose: 1 mg or 2.5 mg. ( 2.1 ) May repeat dose after 4 hours if needed; not to exceed 5 mg in any 24- hour period. ( 2.1 ) Mild or moderate renal or hepatic impairment: recommended starting dose is 1 mg not to exceed 2.5 mg in any 24-hour period. ( 2.2 , 2.3 ) 2.1 Dosing Information The recommended dose of naratriptan tablets is 1 mg or 2.5 mg. If the migraine returns or if the patient has only partial response, the dose may be repeated once after 4 hours, for a maximum dose of 5 mg in a 24-hour period. The safety of treating an average of more than 4 migraine attacks in a 30-day period has not been established. 2.2 Dosage Adjustment in Patients With Renal Impairment Naratriptan tablets are contraindicated in patients with severe renal impairment (creatinine clearance: <15 mL/min) because of decreased clearance of the drug [see Contraindications (4) , Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ]. In patients with mild to moderate renal impairment, the maximum daily dose should not exceed 2.5 mg over a 24-hour period and a 1-mg starting dose is recommended [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ]. 2.3 Dosage Adjustment in Patients With Hepatic Impairment Naratriptan tablets are contraindicated in patients with severe hepatic impairment (Child-Pugh Grade C) because of decreased clearance [see Contraindications (4) , Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ].

Myocardial ischemia/infarction and Prinzmetal's angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. ( 5.1 ) Arrhythmias: Discontinue naratriptan if occurs . ( 5.2 ) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for CAD in patients at high risk. ( 5.3 ) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue naratriptan if occurs . ( 5.4 ) Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue naratriptan if occurs. ( 5.5 ) Medication overuse headache: Detoxification may be necessary. ( 5.6 ) Serotonin syndrome: Discontinue naratriptan if occurs. ( 5.7 ) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina Naratriptan is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of naratriptan. Some of these reactions occurred in patients without known CAD. Naratriptan may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving naratriptan. If there is evidence of CAD or coronary artery vasospasm, naratriptan is contraindicated.

The following adverse reactions are discussed in more detail in other sections of the prescribing information: Myocardial ischemia, myocardial infarction, and Prinzmetal's angina [see Warnings and Precautions (5.1 ) ] Arrhythmias [see Warnings and Precautions (5.2) ] Chest, throat, neck, and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.3) ] Cerebrovascular events [see Warnings and Precautions (5.4) ] Other vasospasm reactions [s ee Warnings and Precautions (5.5) ] Medication overuse headache [see Warnings and Precautions (5.6) ] Serotonin syndrome [see Warnings and Precautions (5.7) ] Increase in blood pressure [see Warnings and Precautions (5.8) ] Hypersensitivity reactions [see Contraindications (4) , Warnings and Precautions (5.9) ] Most common adverse reactions (≥2% and >placebo) were paresthesias, nausea, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a long-term open-label trial where patients were allowed to treat multiple migraine attacks for up to 1 year, 15 patients (3.6%) discontinued treatment due to adverse reactions.

Pregnancy: Based on animal data, may cause fetal harm. (8.1) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of naratriptan in pregnant women. Data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have documented outcomes in women exposed to naratriptan during pregnancy; however, due to small sample sizes, no definitive conclusions can be drawn regarding the risk of birth defects following exposure to naratriptan [ see Data ]. In animal studies, naratriptan produced developmental toxicity (including embryolethality and fetal abnormalities) when administered to pregnant rats and rabbits. The lowest doses producing evidence of developmental toxicity in animals were associated with plasma exposures 2.5 (rabbit) to 11 (rat) times that in humans at the maximum recommended daily dose (MRDD) [ see Data ]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and of miscarriage was 17%, which were similar to rates reported in women without migraine.

Metabolism

Absorption: Naratriptan is well absorbed, with about 70% oral bioavailability. Following administration of a 2.5-mg tablet, the peak concentrations are obtained in 2 to 3 hours.

Adverse reactions observed after overdoses of up to 25 mg included increases in blood pressure resulting in lightheadedness, neck tension, tiredness, and loss of coordination. Also, ischemic ECG changes likely due to coronary artery vasospasm have been reported. The elimination half-life of naratriptan is about 6 hours [see C linical Pharmacology (12.3) ], and therefore monitoring of patients after overdose with naratriptan should continue for at least 24 hours or while symptoms or signs persist. There is no specific antidote to naratriptan. It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentrations of naratriptan.

• Jul 7, 2010ANDAANDA090381Hikma
• Feb 28, 2011ANDAANDA200502Heritage
• Apr 30, 2012ANDAANDA091441Orbion Pharms

1. 1Drug Ineffective17913%
2. 2Migraine1158.5%
3. 3Nausea1047.7%
4. 4Headache957.1%
5. 5Fatigue675.0%
6. 6Dizziness614.5%
7. 7Vomiting594.4%
8. 8Off Label Use574.2%
9. 9Diarrhoea544.0%
10. 10Pain503.7%
11. 11Pyrexia483.6%
12. 12Anxiety413.0%
13. 13Malaise403.0%
14. 14Rash403.0%
15. 15Feeling Abnormal382.8%

The 10 most recently updated of 16 ClinicalTrials.gov registrations naming Naratriptan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Treatments of Migraine with Triptans in Individuals with Elevated Cardiovascular Risk and in Pregnant Women
  Completed · Observational · 68,419 enrolled · Mayo Clinic
  NCT05854992updated 2024-12-02
• Status Migrainosus - Differentiating Between Responders and Non-responders
  Unknown · Phase 1 · Phase 2 · Interventional · 50 enrolled · Hartford HealthCare
  NCT03066544updated 2018-08-31
• Does Treximet Improve Productivity and Patient Satisfaction Due to Sustained Response and Consistency of Response?
  Completed · Phase 4 · Interventional · 60 enrolled · The Cleveland Clinic
  NCT01086358updated 2018-05-01
• Bioequivalency Study of Naratriptan Hydrochloride 2.5 mg Under Fasted Conditions
  Completed · Interventional · 35 enrolled · Roxane Laboratories
  NCT01161667updated 2018-01-23
• Bioequivalency Study of Naratriptan Hydrochloride 2.5 mg Under Fed Conditions
  Completed · Interventional · 33 enrolled · Roxane Laboratories
  NCT01161654updated 2018-01-23
• Treximet ™ Pharmacy Budget Impact Model Database Validation Study
  Completed · Observational · 61,737 enrolled · GlaxoSmithKline
  NCT01332500updated 2017-05-30
• Non-steroidal Anti-inflammatory Drugs Alone or With a Triptan and Reports of Transition From Episodic to Chronic Migraine
  Completed · Observational · 11,249 enrolled · GlaxoSmithKline
  NCT01435941updated 2017-05-16
• Efficacy and Safety of a Fixed-dose Combination of Naratriptan and Naproxen in Acute Treatment of Migraine
  Withdrawn · Phase 3 · Interventional · 0 enrolled · Ache Laboratorios Farmaceuticos S.A.
  NCT01390324updated 2016-10-19
• Efficacy and Safety of a Fixed-dose Combination of Naratriptan and Naproxen in Acute Treatment of Migraine.
  Withdrawn · Phase 3 · Interventional · 0 enrolled · Ache Laboratorios Farmaceuticos S.A.
  NCT01726920updated 2016-03-16
• Special Drug Use Investigation for AMERGE® Tablet (Long-term)
  Completed · Observational · 300 enrolled · GlaxoSmithKline
  NCT01332383updated 2015-08-13

Frequently asked questions

How does Naratriptan work?

Naratriptan binds with high affinity to human cloned 5-HT 1B/1D receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (including substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system.

What is Naratriptan used for?

According to FDA labeling, Naratriptan carries indications including: Naratriptan tablets are indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use: Use only if a clear diagnosis of migraine has been established.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Naratriptan?

Naratriptan is classified as Selective serotonin (5HT1) agonists, Serotonin-1b and Serotonin-1d Receptor Agonist, Serotonin 1b Receptor Agonists, Serotonin 1d Receptor Agonists, Serotonin Agonists, Cerebral Arterial Vasoconstriction, Increased Central Nervous System Serotonin Activity.

What are the contraindications for Naratriptan?

Naratriptan labeling lists contraindications including: Naratriptan tablets are contraindicated in patients with: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina [see Warnings and Precautions (5.1) ] Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2) ] History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because such patients are at a higher risk of stroke [see Warnings and Precautions (5.4) ] Peripheral vascular disease [see Warnings and Precautions (5.5) ] Ischemic bowel disease [see Warnings and Precautions (5.5) ] Uncontrolled hypertension [see Warnings and Precautions (5.8) ] Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions ( 7.1 , 7.2 )] Hypersensitivity to naratriptan (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9) ] Severe renal or hepatic impairment [see Use in Specific Populations ( 8.6 , 8.7 ), Cl…. Always consult the full prescribing information and a clinician.