Frovatriptan (Frova) - Uses, Dose, Side effects, MOA, Brands

Frovatriptan (Frova) is a 5 HT-1 receptor agonist commonly called "Triptans". It causes intracranial vasoconstriction and is indicated for the treatment of patients with acute migraine attack. Frovatriptan has a very long half-life compared to other triptans (about five times that of other triptans) and hence, it may be indicated for the short-term prophylaxis of female patients with menstrual migraine.

Frovatriptan (Frova) Uses:

  • Migraines:

    • Adults' acute migraine treatment, either with or without aura
    • Use only as directed; do not use as prophylactic. Use only in patients with a diagnosed condition.
  • Off Label Use of Frovatriptan in Adults:

    • Menstruation-associated migraines (short-term prevention)

Frovatriptan (Frova) Dose in Adults

Note: If no improvement seen consider alternate diagnosis. No safety data of treating more than four events each month.

Frovatriptan (Frova) Dose in the treatment of Migraine:

  • Oral:
    • 2.5 mg as a starting dose; if headache persists, take another dose after 2 hours.
    • The highest daily dose advised is 7.5 mg.

Use in Children:

Not indicated.

Frovatriptan (Frova) Pregnancy Category: C

  • In animal reproduction studies, adverse events were reported. 
  • There are no data for humans. You can use other migraine medications during pregnancy.

Use Frovatriptan while breastfeeding

  • Before starting treatment, analyze the risk-benefit ratio for both mother and baby.

Dose in Kidney Disease:

No dose adjustment is needed.

Frovatriptan (Frova) Dose in Liver disease:

  • Mild to moderate impairment:

    • No dosage adjustment.
  • Severe impairment:

    • No data are available.

Side Effects of Frovatriptan (Frova):

  • Cardiovascular:

    • Flushing
    • Hot Or Cold Flashes
    • Chest Pain
    • Palpitations
  • Central Nervous System:

    • Dizziness
    • Fatigue
    • Headache
    • Paresthesia
    • Drowsiness
    • Anxiety
    • Dysesthesia
    • Hypoesthesia
    • Insomnia
    • Pain
  • Dermatologic:

    • Diaphoresis
  • Gastrointestinal:

    • Xerostomia
    • Nausea
    • Dyspepsia
    • Abdominal Pain
    • Diarrhea
    • Vomiting
  • Neuromuscular & Skeletal:

    • Musculoskeletal Pain
  • Ophthalmic:

    • Visual Disturbance
  • Otic:

    • Tinnitus
  • Respiratory:

    • Rhinitis
    • Sinusitis

Contraindication to Frovatriptan (Frova):

  • Ischemic coronary disease (eg angina pectoris; MI, documented silentischemia)
  • Coronary artery vasospasm including Prinzmetal’s angina;
  • Wolff-Parkinson White syndrome, arrhythmias and other cardiac accessory conduction pathway disorders
  • History of stroke, transient Ischemia Attack, or hemiplegic migraine.
  • Peripheral Vascular Disease;
  • Ischemic bowel disease
  • Hypertension uncontrolled
  • Use of an ergotamine-containing or ergottype 5-HT-1 agonist recently, such as dihydroergotamine, within the previous 24 hours
  • hypersensitivity to any medicine or formula ingredient

Canadian labeling: Additional contraindications not in US labeling

  • Cardiac arrhythmias (especially Tachycardia), valvular and congenital heart diseases, atherosclerotic diseases, and valvular heart disease are all possible.
  • Management of ophthalmoplegic headaches
  • Hepatic impairment severe
  • There is not much evidence of triptan cross-reactivity.
  •  Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

  • Anaphylactoid and Anaphylactic reactions:

    • There may be anaphylaxis, anaphylactoid responses, and hypersensitivity reactions (including edoema).
  • Cardiac events

    • Administration of 5-HT-1 agonist has been associated with cardiac arrest, heart failure, transient ischemia and myocardial injury.
    • Stop side effects developing
    • Patients who suffer chest discomfort, pressure, tightness, or other symptoms that suggest angina should be checked for Prinzmetal's or CAD before continuing with medication.
    • If the patient experiences the same symptoms after treatment, ECG monitoring should be performed.
    • It is not advised for patients with vasospastic or ischemic CAD, Wolff-Parkinson-White syndrome, or arrhythmias linked to various diseases of the cardiac accessory conduction pathways.
  • Cerebrovascular events

    • Contraindicated if you have a history of TIA/CVA.
    • Five-HT-1 agonist administration has been linked to strokes and cerebral/subarachnoid hemorhage (some fatal).
  • High blood pressure

    • Hypertension rarely with end-organ damage, or markedly elevated blood pressure.
    • Contraindicated in conjunction with uncontrolled hypertension
  • Headaches

    • If you take your medication for more than 10 days per month, withdrawal headaches can occur.
  • Vasospasm-related events

    • Raynaud syndrome, gastrointestinal and peripheral vascular infarction, and infarction.
  • Visual effects

    • There have been cases of partial and complete (reversible or irreversible) but no clear relationship.
  • Coronary artery disease

    • Patients at high risk of developing CAD should be avoided (eg, hypertension and hypercholesterolemia; smoking obesity, diabetes, strong family history, men >40 years old, hypertension, smoking, or other factors that could increase the likelihood of developing CAD).
    • Contraindicated for CAD and coronary artery vasospasm
    • Before starting treatment, a cardiac evaluation is required. If you are using long-term treatment, follow up with periodic evaluation.
  • Hepatic impairment

    • There are no data available. Please be careful.

Frovatriptan: Drug Interaction

Risk Factor C (Monitor therapy)

Antiemetics (5HT3 Antagonists)

Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.

Antipsychotic Agents

Serotonin modulators might make antipsychotic drugs more harmful or toxic. Serotonin modulators, in particular, may enhance dopamine blockade, potentially raising the risk for neuroleptic malignant syndrome. Serotonin modulators' serotonergic effects may be strengthened by antipsychotic drugs. Serotonin syndrome might occur from this.

Droxidopa

Droxidopa's hypertensive action may be enhanced by serotonin 5-HT1D receptor antagonists.

Metaxalone

Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.

Methylphenidate

Serotonin modulators' harmful or toxic effects could be exacerbated. In particular, there may be an increased risk of serotonin syndrome or serotonin poisoning.

Metoclopramide

Serotonin modulators may intensify Metoclopramide's harmful or hazardous effects. This could appear as signs of neuroleptic malignant syndrome or serotonin syndrome.

Opioid Agonists

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Serotonin Modulators

May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.

Tedizolid

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

TraMADol

Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

Risk Factor D (Consider therapy modification)

Anti-Parkinson Agents (Monoamine Oxidase Inhibitor)

Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this. If selegiline, rasagiline, or safinamide is taken with a serotonin modulator, keep an eye out for any signs and symptoms of serotonin syndrome or serotonin poisoning. It is not advised to use transdermal selegiline with serotonin modulators.

Linezolid

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely.

Risk Factor X (Avoid combination)

Dapoxetine

May enhance the adverse/toxic effect of Serotonin Modulators.

Ergot Derivatives

May enhance serotonin 5-HT1D receptor antagonists' ability to constrict blood vessels. The vasoconstrictive effects of ergot derivatives may be enhanced by serotonin 5-HT1D receptor antagonists. The exception is nigroline.

Methylene Blue

May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.

SUMAtriptan

The negative/toxic effects of sumatriptan may be increased by serotonin 5-HT1D receptor antagonists.

 

Monitoring parameters:

  • Severity of headache severity
  • bloodpressure
  • signs/symptoms of angina. Periodic cardiac function assessment inwin patients with long duration of therapy and multiple cardiovascular risk factors.
  • signs/symptoms of serotonin syndrome and hypersensitivity reactions.

How to administer Frovatriptan (Frova)?

  • Take when symptoms appear. Wash down with lots of fluids

Mechanism of action of Frovatriptan (Frova):

  • Selective serotonin antagonist (5-HT-1B or 5-HT-1D receptors), in the cranial arteries. 
  • Reduces migraines due to migrane headaches by increasing blood flow and decreasing inflammation.

Protein binding:

  • ~15%

Metabolism:

  • Primarily hepatic via CYP1A2

Bioavailability:

  • Male: ~20%;
  • Female: ~30%

Half-life elimination:

  • ~26 hours

Time to peak:

  • 2-4 hours

Excretion:

  • Feces (62%);
  • Urine (32%)

International Brand Names of Frovatriptan:

  • Frova
  • APO-Frovatriptan
  • TEVA-Frovatriptan
  • Allegro
  • Auradol
  • Eumitan
  • Forvey
  • Fromen
  • Fromena
  • Fromirex
  • Frovatex
  • Frovex
  • Menamig
  • Menatriptan
  • Migard
  • Miguard
  • Relieva
  • Tigreat

Frovatriptan Brands Names in Pakistan:

No Brands Available in Pakistan.