Triptan, selective 5HT1B/1D receptor agonist
Brand names: Frova
Updated · Methodology
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Migraine in nursing mothers with menstrually-related pattern (short prophylaxis 5–6 days per cycle). Dose 2.5 mg 1–2 times daily. For routine acute attacks, not first-line due to long T½.
Sources
ICD-10: G43.9 · ICD-11: 8A80.Z
Activates 5HT1B/1D receptors on dural vessels and the trigeminal system. The ~26-hour half-life – the longest among triptans – makes it convenient for short-course prophylaxis of menstrual migraine. CYP1A2 metabolism.
AEMPS summary of product characteristics (section 4.6): there are no or limited data on frovatriptan use in pregnant women. Animal studies have shown reproductive toxicity, and the potential risk for humans is unknown. Frovatriptan is not recommended during pregnancy or in women of childbearing potential who do not use contraception, unless clearly necessary.
Compatible with caution. Hale L3. T½ 26 h – longest among triptans, risk of milk accumulation. Used for menstrually-related migraine, not daily. In nursing mothers, prefer sumatriptan or eletriptan.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
2 pairs found. Sorted from critical to minor.
Mechanism
Frovatriptan constricts cranial vessels through serotonin receptors. Ergotamine also constricts arteries, and the effects of the two drugs add up. The Spanish frovatriptan summary of product characteristics (SmPC) warns of high blood pressure and coronary artery spasm when both drugs are taken for the same migraine attack. Ergotamine on its own can cause myocardial ischaemia, or rarely infarction, even in people with no known heart disease. Vasospasm after ergot drugs can be prolonged. The risk comes from the effect on vessels, not from drug levels. With ergotamine, the area under the curve and peak concentration of frovatriptan actually fell, by about 25%.
Symptoms
Coronary artery spasm causes chest pain, pressure or tightness, sometimes severe and spreading to the throat, neck or jaw, and can lead to myocardial infarction. Serious arrhythmias such as ventricular tachycardia and ventricular fibrillation have been reported within a few hours of taking drugs of this group. Vasospasm from ergotamine causes numbness and tingling in the fingers and toes, headache and pain over the heart. With severe spasm, the limbs turn blue and their pulses disappear. Spasm of other arteries causes Raynaud's syndrome and bowel ischaemia with abdominal pain and bloody diarrhoea. Splenic infarction has also been reported. In rare cases, blood pressure rises to a hypertensive crisis.
Management
The frovatriptan documents of the Spanish Agency of Medicines and Medical Devices (AEMPS) and the US Food and Drug Administration () contraindicate the combination. The Spanish summary of product characteristics (SmPC) for ergotamine with caffeine contraindicates all triptans (AEMPS). Keep at least 24 hours between the two drugs, in either order (frovatriptan SmPC, AEMPS, and label, FDA). If ergotamine has not stopped the attack, do not add a triptan for the same attack (ergotamine with caffeine SmPC, AEMPS). If chest pain or tightness suggesting cardiac ischaemia appears after a frovatriptan dose, give no further doses and examine the patient further (frovatriptan SmPC, AEMPS). Stop ergotamine at once if numbness or tingling in the fingers, pain over the heart or other signs of vasospasm appear (ergotamine with caffeine SmPC, AEMPS). Stop frovatriptan if arrhythmias occur, and monitor blood pressure during treatment (frovatriptan label, FDA). If abdominal pain with blood in the stool or white fingers appear, rule out vasospasm before the patient takes frovatriptan again (frovatriptan label, FDA). Taking ergotamine, triptans or both on 10 or more days a month can cause medication overuse headache, with more frequent attacks (frovatriptan label, FDA).
Sources
Mechanism
Frovatriptan is a serotonin agonist, CYP1A2 substrate. With phenelzine – fatal serotonin syndrome.
Symptoms
Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.
Management
Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.
Sources
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, an ergotamine containing or ergot-type medication such as dihydroergotamine (DHE) or methysergide [see Drug…»FDA, section 4 · Open on DailyMed
«está contraindicada la administración concomitante de frovatriptán con ergotamina o derivados de la ergotamina (incluida la metisergida) u otros agonistas del receptor 5-hidroxitriptamina (5-HT 1 ).»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, an ergotamine containing or ergot-type medication such as dihydroergotamine (DHE) or methysergide [see Drug…»FDA, section 4 · Open on DailyMed
«Inhibidores de la monoaminooxidasa: Frovatriptán no es un substrato de la MAO-A. No puede ser excluido un riesgo potencial de síndrome serotoninérgico o hipertensión (ver sección 5.2).»AEMPS, section 4.5 · Open on CIMA
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Al igual que otros agonistas del receptor 5-HT 1 , frovatriptán no debe administrarse a pacientes con riesgo de cardiopatía isquémica (CAD), incluidos los pacientes con hábito tabáquico o pacientes…»AEMPS, section 4.4 · Open on CIMA
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Inhibidores selectivos de la recaptación de serotonina (citalopram, fluoxetina, fluvoxamina, paroxetina, sertralina).»AEMPS, section 4.5 · Open on CIMA
«Anticonceptivos orales: En mujeres que toman anticonceptivos orales, la concentración de frovatriptán es un 30% superior a la de mujeres que no toman anticonceptivos orales. No se ha registrado una…»AEMPS, section 4.5 · Open on CIMA
«5-HT 1B/FDA, section 7 · Open on DailyMed
«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
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Frovatriptan 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.
Common side effects of Frovatriptan (≥ 1 in 100): Dizziness, Somnolence, Hot flushes, Paraesthesia, Chest or throat tightness (non-ischaemic), Nausea. See the Safety section for uncommon and serious reactions.
AEMPS summary of product characteristics (section 4.6): there are no or limited data on frovatriptan use in pregnant women. Animal studies have shown reproductive toxicity, and the potential risk for humans is unknown. Frovatriptan is not recommended during pregnancy or in women of childbearing potential who do not use contraception, unless clearly necessary.
Compatible with caution. Hale L3. T½ 26 h – longest among triptans, risk of milk accumulation. Used for menstrually-related migraine, not daily. In nursing mothers, prefer sumatriptan or eletriptan.
Frovatriptan 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.
Direct links to regulator labels. Open in a new tab.
Meperidine, Metamizole sodium, Morphine, Naratriptan, Palmitoylethanolamide, Tramadol, Buprenorphine (transdermal), Oxycodone