Evigrade

Naratriptan

AEMPS

Triptan, selective 5HT1B/1D receptor agonist

ATC code: N02CC02

Brand names: Amerge

Updated · Methodology

Indications

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Activates 5HT1B/1D receptors on meningeal vessels and the trigeminal system. Acts more gently and slowly than sumatriptan, with onset in 1–2 hours and lower recurrence rate thanks to a ~6-hour half-life. Mostly renal excretion, minimal CYP metabolism.

Safety

Contraindications

  • Hypersensitivity to triptans or sulfonamides
  • Ischaemic heart disease, prior myocardial infarction, Prinzmetal angina
  • Uncontrolled hypertension
  • Cerebrovascular disease and prior transient ischaemic attack
  • Peripheral arterial disease
  • Co-administration with ergotamine, dihydroergotamine or another triptan within 24 hours
  • Co-administration with MAOIs within 14 days
  • Severe hepatic impairment

Serious adverse effects

  • Coronary vasospasm with myocardial infarction
  • Ischaemic stroke and transient ischaemic attack
  • Serotonin syndrome when combined with SSRIs/SNRIs/TCAs
  • Hypersensitivity reactions including anaphylaxis
  • Medication-overuse headache (use >10 days per month)

Common adverse effects

  • Dizziness
  • Somnolence
  • Hot flushes
  • Paraesthesia
  • Chest or throat tightness (non-ischaemic)
  • Nausea
  • Dry mouth

Pregnancy: can you take Naratriptan?

AEMPS summary of product characteristics (section 4.6): animal studies do not indicate direct teratogenic effects, but delayed fetal ossification and possible effects on embryo viability were seen in rabbits. Post-marketing data from several prospective pregnancy registries cover fewer than 60 women exposed to naratriptan, and the sample is too small for definitive conclusions on the risk of birth defects. Naratriptan is used only if the expected benefit to the mother outweighs any possible risk to the fetus.

Breastfeeding: can you take Naratriptan?

Hale L3 · Probably compatible, limited data

Compatible with caution. Hale L3. T½ 6 h – longer than sumatriptan. Milk accumulation possible with repeated dosing. Prefer shorter-acting triptans.

Maternal half-life
6 h
Maternal peak time
2.5 h

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

2 pairs found. Sorted from critical to minor.

CriticalDihydroergotamineErgot alkaloid, 5-HT1B/1D and alpha-adrenoceptor agonist

Mechanism

Both drugs constrict blood vessels. Naratriptan stimulates serotonin receptors in the walls of cranial vessels. Dihydroergotamine acts on the same serotonin receptors and also on alpha-adrenergic receptors. Ergot drugs cause prolonged vasospasm and triptans can cause coronary artery spasm, so the vasoconstrictor effects of the two drugs may add up. Data on the combination are limited. In these data, naratriptan with ergotamine, dihydroergotamine or sumatriptan did not change blood pressure, heart rate or the electrocardiogram, and did not affect naratriptan blood levels. Still, the combination may in theory raise the risk of coronary artery spasm.

Symptoms

Tightness, pain or pressure in the chest, throat, neck and jaw is common after naratriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, and also after dihydroergotamine. Spasm of other arteries causes numb, cold, pale or bluish fingers and toes, muscle pain, abdominal pain with bloody diarrhoea from bowel ischaemia, and sometimes splenic infarction. Both drugs can raise blood pressure sharply, and hypertensive crisis has been reported after triptans.

Management

The naratriptan summary of product characteristics (SmPC) from the Spanish Agency of Medicines and Medical Devices (AEMPS) contraindicates ergotamine and its derivatives (sections 4.3 and 4.5). The naratriptan and dihydroergotamine labels from the US Food and Drug Administration () also contraindicate the combination. Keep at least 24 hours between the two drugs, in either order (naratriptan and dihydroergotamine labels, FDA). The Spanish naratriptan SmPC sets the same 24-hour interval in both directions for ergotamine preparations (AEMPS). If chest pain or tightness spreading to the throat appears after a naratriptan dose and suggests cardiac ischaemia, give no further doses and evaluate the patient (naratriptan SmPC, AEMPS). If signs of vasospasm appear, such as cold, pale or bluish fingers, muscle pain or abdominal pain with blood in the stool, stop dihydroergotamine at once (dihydroergotamine label, FDA). Rule out vasospasm before the next naratriptan dose (naratriptan label, FDA). Monitor blood pressure (naratriptan label, FDA). Both drugs are contraindicated in uncontrolled hypertension (naratriptan and dihydroergotamine labels, FDA), and naratriptan also in moderate or severe hypertension (naratriptan SmPC, AEMPS). Taking triptans and ergot drugs, alone or together, on 10 or more days a month can lead to medication overuse headache (naratriptan and dihydroergotamine labels, FDA).

Pair details →Dihydroergotamine →

CriticalPhenelzineAntidepressant, irreversible non-selective monoamine oxidase inhibitor (MAO-A and MAO-B)

Mechanism

Naratriptan is a serotonin agonist. With phenelzine – fatal serotonin syndrome.

Symptoms

Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.

Management

Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.

Pair details →Phenelzine →

Label mentions13 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • «La administración concomitante de naratriptán con ergotamina, preparados que contengan ergotamina, dihidroergotamina (DHE) o sumatrip tán no produjo efectos clínicamente significativos en la presión…»

    AEMPS, section 4.5 · Open on CIMA

  • «CONTRAINDICATIONS: 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…»

    FDA, section 4 · Open on DailyMed

  • CriticalErgotamine
    «La administración concomitante de ergotamina, derivados de la ergotamina (incluida la metisergida) y cualquier triptán/agonista del receptor 5-hidroxitriptamina 1 (5-HT 1 ) con naratriptán está…»

    AEMPS, section 4.3 · Open on CIMA

  • CriticalErgotamine
    «CONTRAINDICATIONS: 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…»

    FDA, section 4 · Open on DailyMed

  • Minoranticonceptivos hormonalesclass named in the label
    «Los anticonceptivos orales reducen en un 30 % el aclaramiento total de naratriptán y el tabaquismo aumenta el aclaramiento total en un 30 %. No obstante, no se requiere ningún ajuste de dosis.»

    AEMPS, section 4.5 · Open on CIMA

  • antidepresivos tricíclicosclass named in the label
    «No hay pruebas de una interacción farmacocinética con β -bloqueantes, antidepresivos tricíclicos e inhibidores selectivos de la recaptación de serotonina, alcohol o alimentos.»

    AEMPS, section 4.5 · Open on CIMA

  • betabloqueantesclass named in the label
    «No hay pruebas de una interacción farmacocinética con β -bloqueantes, antidepresivos tricíclicos e inhibidores selectivos de la recaptación de serotonina, alcohol o alimentos.»

    AEMPS, section 4.5 · Open on CIMA

  • ISRSclass named in the label
    «Se han comunicado casos de síndrome serotoninérgico (incluyendo estado mental alterado, inestabilidad autonómica y anomalías neuromusculares) tras el tratamiento concomitante con triptanes e…»

    AEMPS, section 4.5 · Open on CIMA

  • medicamentos serotoninérgicosclass named in the label
    «Se han comunicado casos de síndrome serotoninérgico (incluyendo estado mental alterado, inestabilidad autonómica y anomalías neuromusculares) tras el tratamiento concomitante con triptanes e…»

    AEMPS, section 4.5 · Open on CIMA

  • SSRIs/SNRIsclass named in the label
    «Other 5-HT 1 Agonists: Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome»

    FDA, section 7 · Open on DailyMed

From other drugs’ labels

  • CriticalMoclobemide
    «La administración conjunta de Manerix con triptanos está contraindicada ya que éstos son potentes receptores agonistas serotoninérgicos metabolizados por las monoaminooxidasas (MAOs) y varios enzimas…»

    AEMPS, section 4.5 · Open on CIMA

  • CriticalRizatriptan
    «Ergotamina, derivados de la ergotamina (incluyendo metisérgida) y otros agonistas de los receptores 5 HT 1B/1D : Debido a un efecto aditivo, el uso concomitante de rizatriptán y ergotamina, derivados…»

    AEMPS, section 4.5 · Open on CIMA

  • CriticalSelegiline
    «Agonistas de la serotonina: La selegilina no debe utilizarse en combinación con agonistas de la serotonina (por ejemplo, sumatriptán, naratriptán, zolmitriptán, rizatriptán, lasmiditán) debido al…»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Naratriptan used for?

Naratriptan is evaluated for the following indications with varying evidence strength: Migraine during breastfeeding (evidence tier C). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Naratriptan?

Common side effects of Naratriptan (≥ 1 in 100): Dizziness, Somnolence, Hot flushes, Paraesthesia, Chest or throat tightness (non-ischaemic), Nausea. See the Safety section for uncommon and serious reactions.

Is Naratriptan safe during pregnancy?

AEMPS summary of product characteristics (section 4.6): animal studies do not indicate direct teratogenic effects, but delayed fetal ossification and possible effects on embryo viability were seen in rabbits. Post-marketing data from several prospective pregnancy registries cover fewer than 60 women exposed to naratriptan, and the sample is too small for definitive conclusions on the risk of birth defects. Naratriptan is used only if the expected benefit to the mother outweighs any possible risk to the fetus.

Is Naratriptan compatible with breastfeeding?

Compatible with caution. Hale L3. T½ 6 h – longer than sumatriptan. Milk accumulation possible with repeated dosing. Prefer shorter-acting triptans.

Who should not take Naratriptan?

Naratriptan is contraindicated in: Hypersensitivity to triptans or sulfonamides; Ischaemic heart disease, prior myocardial infarction, Prinzmetal angina; Uncontrolled hypertension; Cerebrovascular disease and prior transient ischaemic attack; Peripheral arterial disease. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

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