Naratriptan

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Naratriptan
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

Disclaimer

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Overview

Naratriptan is an antimigraine and5-HT1 serotonin receptor agonist that is FDA approved for the treatment of migraine with or without aura in adults.. Common adverse reactions include paresthesias, nausea, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Naratriptan FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Naratriptan in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Naratriptan in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Naratriptan FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Naratriptan in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Naratriptan in pediatric patients.

Contraindications

AMERGE is contraindicated in patients with:

Warnings

Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina

AMERGE 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 AMERGE. Some of these reactions occurred in patients without known CAD. AMERGE 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 AMERGE. If there is evidence of CAD or coronary artery vasospasm, AMERGE is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of AMERGE in a medically supervised setting and performing an electrocardiogram (ECG) immediately following administration of AMERGE. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of AMERGE.

Arrhythmias

Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue AMERGE if these disturbances occur. AMERGE is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders.

Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure

Sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw commonly occur after treatment with AMERGE and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. 5-HT1 agonists, including AMERGE, are contraindicated in patients with CAD and those with Prinzmetal’s variant angina.

Cerebrovascular Events

Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue AMERGE if a cerebrovascular event occurs.

Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine, exclude other potentially serious neurological conditions. AMERGE is contraindicated in patients with a history of stroke or TIA.

Other Vasospasm Reactions

AMERGE may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud’s syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional doses of AMERGE.

Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 agonists have not been clearly established.

Medication Overuse Headache

Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

Serotonin Syndrome

Serotonin syndrome may occur with AMERGE, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue AMERGE if serotonin syndrome is suspected.

Increase in Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with AMERGE. AMERGE is contraindicated in patients with uncontrolled hypertension.

Anaphylactic/Anaphylactoid Reactions

There have been reports of anaphylaxis and anaphylactoid and hypersensitivity reactions, including angioedema, in patients receiving AMERGE. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. AMERGE is contraindicated in patients with a history of hypersensitivity reaction to AMERGE.

Adverse Reactions

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 to 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.

In controlled clinical trials, the most common adverse reactions were paresthesias, dizziness, drowsiness, malaise/fatigue, and throat/neck symptoms, which occurred at a rate of 2% and at least 2 times placebo rate.

Table 1 lists the adverse reactions that occurred in 5 placebo-controlled clinical trials of approximately 1,752 exposures to placebo and AMERGE in adult patients with migraine. Only reactions that occurred at a frequency of 2% or more in groups treated with AMERGE 2.5 mg and that occurred at a frequency greater than the placebo group in the 5 pooled trials are included in Table 1.

Postmarketing Experience

There is limited information regarding Naratriptan Postmarketing Experience in the drug label.

Drug Interactions

Ergot-Containing Drugs

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and AMERGE within 24 hours of each other is contraindicated.

Other 5-HT1 Agonists

Concomitant use of other 5-HT1B/1D agonists (including triptans) within 24 hours of treatment with AMERGE is contraindicated because the risk of vasospastic reactions may be additive.

Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome

Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C There are no adequate and well-controlled trials in pregnant women. AMERGE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In reproductive toxicity studies in rats and rabbits, oral administration of naratriptan was associated with developmental toxicity (embryolethality, fetal abnormalities, pup mortality, offspring growth retardation) at doses producing maternal plasma drug exposures as low as 11 and 2.5 times, respectively, the exposure in humans receiving the maximum recommended daily dose (MRDD) of 5 mg.

When naratriptan was administered to pregnant rats during the period of organogenesis at doses of 10, 60, or 340 mg/kg/day, there was a dose-related increase in embryonic death; incidences of fetal structural variations (incomplete/irregular ossification of skull bones, sternebrae, ribs) were increased at all doses. The maternal plasma exposures (AUC) at these doses were approximately 11, 70, and 470 times the exposure in humans at the MRDD. The high dose was maternally toxic, as evidenced by decreased maternal body weight gain during gestation. A no-effect dose for developmental toxicity in rats exposed during organogenesis was not established.

When naratriptan was administered orally (1, 5, or 30 mg/kg/day) to pregnant Dutch rabbits throughout organogenesis, the incidence of a specific fetal skeletal malformation (fused sternebrae) was increased at the high dose, and increased incidences of embryonic death and fetal variations (major blood vessel variations, supernumerary ribs, incomplete skeletal ossification) were observed at all doses (4, 20, and 120 times, respectively, the MRDD on a body surface area basis). Maternal toxicity (decreased body weight gain) was evident at the high dose in this study. In a similar study in New Zealand White rabbits (1, 5, or 30 mg/kg/day throughout organogenesis), decreased fetal weights and increased incidences of fetal skeletal variations were observed at all doses (maternal exposures equivalent to 2.5, 19, and 140 times exposure in humans receiving the MRDD), while maternal body weight gain was reduced at 5 mg/kg or greater. A no-effect dose for developmental toxicity in rabbits exposed during organogenesis was not established.

When female rats were treated orally with naratriptan (10, 60, or 340 mg/kg/day) during late gestation and lactation, offspring behavioral impairment (tremors) and decreased offspring viability and growth were observed at doses of 60 mg/kg or greater, while maternal toxicity occurred only at the highest dose. Maternal exposures at the no-effect dose for developmental effects in this study were approximately 11 times the exposure in humans receiving the MRDD.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Naratriptan in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Naratriptan during labor and delivery.

Nursing Mothers

Naratriptan is excreted in rat milk. It is not known whether naratriptan is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from AMERGE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Therefore, AMERGE is not recommended for use in patients younger than 18 years of age.

One controlled clinical trial evaluated AMERGE (0.25 to 2.5 mg) in 300 adolescent migraineurs aged 12 to 17 years who received at least 1 dose of AMERGE for an acute migraine. In this study, 54% of the patients were female and 89% were Caucasian. There were no statistically significant differences between any of the treatment groups. The headache response rates at 4 hours (n) were 65% (n = 74), 67% (n = 78), and 64% (n = 70) for placebo, 1-mg, and 2.5-mg groups, respectively. This trial did not establish the efficacy of AMERGE compared with placebo in the treatment of migraine in adolescents. Adverse reactions observed in this clinical trial were similar in nature to those reported in clinical trials in adults.

Geriatic Use

Clinical trials of AMERGE did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Naratriptan is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in elderly patients who have reduced renal function. In addition, elderly patients are more likely to have decreased hepatic function, they are at higher risk for CAD, and blood pressure increases may be more pronounced in the elderly.

A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving AMERGE

Gender

There is no FDA guidance on the use of Naratriptan with respect to specific gender populations.

Race

There is no FDA guidance on the use of Naratriptan with respect to specific racial populations.

Renal Impairment

The use of AMERGE is contraindicated in patients with severe renal impairment (creatinine clearance: <15 mL/min) because of decreased clearance of the drug. In patients with mild to moderate renal impairment, the recommended starting dose is 1 mg, and the maximum daily dose should not exceed 2.5 mg over a 24-hour period.

Hepatic Impairment

The use of AMERGE is contraindicated in patients with severe hepatic impairment (Child-Pugh grade C) because of decreased clearance. In patients with mild or moderate hepatic impairment (Child-Pugh grade A or B), the recommendedstarting dose is 1 mg, and the maximum daily dose should not exceed 2.5 mg over a 24-hour period.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Naratriptan in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Naratriptan in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Naratriptan Administration in the drug label.

Monitoring

There is limited information regarding Naratriptan Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Naratriptan and IV administrations.

Overdosage

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 , and therefore monitoring of patients after overdose with AMERGE 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.

Pharmacology

Template:Px
Naratriptan
Systematic (IUPAC) name
N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide
Identifiers
CAS number 121679-13-8
ATC code N02CC02
PubChem 4440
DrugBank DB00952
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 335.465 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 74%
Metabolism Hepatic
Half life 5-8 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

B3(AU) C(US)

Legal status

Template:Unicode Prescription only

Routes Oral

Mechanism of Action

There is limited information regarding Naratriptan Mechanism of Action in the drug label.

Structure

Naratriptan hydrochloride is chemically designated as N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide monohydrochloride, and it has the following structure:

Pharmacodynamics

There is limited information regarding Naratriptan Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Naratriptan Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Naratriptan Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Naratriptan Clinical Studies in the drug label.

How Supplied

There is limited information regarding Naratriptan How Supplied in the drug label.

Storage

There is limited information regarding Naratriptan Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Naratriptan Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Naratriptan interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Naratriptan Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Naratriptan Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Naratriptan
NARATRIPTAN tablet® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Patient Counseling Information
Labels and Packages
Clinical Trials on Naratriptan
ClinicalTrials.gov
Naratriptan
Clinical data
Trade namesAmerge
AHFS/Drugs.comMonograph
MedlinePlusa601083
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability74%
MetabolismHepatic
Elimination half-life5-8 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC17H25N3O2S
Molar mass335.465 g/mol
3D model (JSmol)
  (verify)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

For patient information about Naratriptan, click here.

Synonyms / Brand Names: NARATRIPTAN

Overview

Naratriptan (trade names include Amerge and Naramig) is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. Naratriptan is available in 2.5 mg tablets. It is a selective 5-HT1 receptor subtype agonist.

Category

Serotonin Receptor Agonists; Antimigraine Agents

FDA Package Insert

Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages

Indication

Naratriptan is used for the treatment of the acute migraine attacks and the symptoms of migraine, including severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound or light.[1]

Mechanism of action

The causes of migraine are not clearly understood; however, the efficacy of naratriptans and other triptans is believed to be due to their activity as 5HT (serotonin) agonists.

Efficacy

A meta-analysis of 53 clinical trials has shown that all triptans are effective for treating migraine at marketed doses and that naratriptan, although less effective than sumatriptan and rizatriptan was more effective than placebo in reducing migraine symptoms at two hours[2] and efficacy was demonstrated in almost two thirds of subjects after four hours of treatment.[3]

Side effects

Side effects include: dizziness, drowsiness, tingling of the hands or feet, nausea, dry mouth and unsteadiness. If these effects persist or worsen, notify your doctor promptly. Side-effects which are unlikely and which should be promptly reported include: chest pain/pressure, throat pain/pressure, unusually fast/slow/irregular pulse, one-sided muscle weakness, vision problems, cold/bluish hands or feet, stomach pain, bloody diarrhea, mental/mood changes, and fainting. In the unlikely event you have a serious allergic reaction to this drug, seek immediate medical attention. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing (swelling of the throat).

The use of naratriptan with MAOIs and serotonergic drugs may result in the life threatening serotonin syndrome. Make sure your doctor/pharmacist is aware of all your current medications (including as needed medications) before taking this drug. [4]

Exclusivity

In the United States, the Food and Drug Administration (FDA) approved naratriptan on February 11, 1998.[5] It was covered by U.S. Patent no. 4997841; the FDA lists the patent as expiring on July 7, 2010.[5][6]

In July 2010, in the wake of the patent expiration, several drug manufacturers, including Roxane Labs,[7] Sandoz[8] and Teva Pharmaceuticals,[9] announced that they were launching generic Naratriptan medications.

The drug continues to be covered by European patent 0303507 in Germany, Spain, France and the United Kingdom through March 10, 2012,[10] and by Australian patent 611469 in Australia through June 17, 2013.[10] It had previously been covered by Canadian patent 1210968; but both Sandoz and Novopharm have offered generic equivalents in Canada since that patent's expiration December 1, 2009.[10]

References

  1. Medline Plus Drug Information for Naratriptan Accessed 6 August 2009
  2. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 2002 Oct;22(8):633-58.
  3. Efficacy of naratriptan tablets in the acute treatment of migraine: A dose-ranging study. Clin Ther 2000 Aug;22(8):970-80.
  4. (( cite web | url = http://www.drugs.com/cdi/naratriptan.html ))
  5. 5.0 5.1 FDA AccessData entry for Naratriptan Hydrochloride, accessed September 8, 2008
  6. U.S. Patent no. 4997841, Alexander W. Oxford, et al., Indole Derivatives, March 5, 1991
  7. DeArment, Alaric (2010-07-09). "Roxane launches generic Amerge, Arimidex". Drug Store News. Retrieved 2010-07-23.
  8. DeArment, Alaric (2010-07-12). "Sandoz launches generic Amerge". Drug Store News. Retrieved 2010-07-23.
  9. DeArment, Alaric (2010-07-14). "Teva launches generic Amerge". Drug Store News. Retrieved 2010-07-23.
  10. 10.0 10.1 10.2 Oh, Dae (June 2010). "Drug In Focus: Naratriptan". GenericsWeb. Retrieved 2010-12-15.

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