frovatriptan

Action and Spectrum

Actions and spectrum: 

frovatriptan is a selective serotonin receptor agonist used for the acute treatment of migraine headaches. It binds to the 5-HT1B and 5-HT1D receptors, which are located on the blood vessels and nerve endings in the brain, leading to vasoconstriction and inhibition of pro-inflammatory neuropeptide release.

This action helps to reduce the pain and other symptoms of migraine attacks. frovatriptan has a longer half-life compared to other triptans, which makes it useful for the treatment of menstrual-related migraines. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Chest pain (>2%)  

Frequency not defined 

Dizziness 

Flushing 

Hot or cold sensation 

Somnolence 

Nausea 

Skeletal pain 

Fatigue 

Headache 

Paresthesia 

Dyspepsia 

Xerostomia 

Myocardial infarction 

Black Box Warning

Black Box Warning: 

There are no black box warnings for frovatriptan. However, like all triptans, frovatriptan should not be used within 24 hours of using another triptan or an ergotamine-containing medication due to the risk of developing serotonin syndrome. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity to frovatriptan or any of the components of the formulation 
• Ischemic heart disease (angina pectoris, history of myocardial infarction, documented silent ischemia, Prinzmetal’s angina) 
• Coronary artery vasospasm, including Prinzmetal’s angina 
• Uncontrolled hypertension 
• Peripheral vascular disease, including ischemic bowel disease 
• Severe hepatic impairment (Child-Pugh grade C) 
• Concurrent use or recent use (within 24 hours) of another 5-HT1 agonist, ergotamine-containing, or ergot-type medication (like dihydroergotamine, ergotamine tartrate, methysergide), or MAO inhibitors 
• Use within 72 hours of potent CYP1A2 inhibitors such as fluvoxamine, ciprofloxacin, and enoxacin, as frovatriptan clearance may be decreased and plasma concentrations may be increased, potentially causing adverse reactions.

Caution: 

• Cardiovascular disease: frovatriptan can cause the narrowing of blood vessels and increase blood pressure. Hence, it should be used with caution in patients with coronary artery disease, angina, or myocardial infarction. 
• Hepatic impairment: The use of frovatriptan should be avoided in patients with severe liver disease. Patients with hepatic impairment should use frovatriptan with caution. 
• Renal impairment: frovatriptan should be used with caution in patients with renal impairment. In such cases, a lower dose may be required. 
• Elderly patients: Elderly patients are more susceptible to the side effects of frovatriptan, such as dizziness and fatigue. Therefore, caution should be exercised when using this medication in older patients. 
• Pregnancy and breast-feeding: The safety of frovatriptan during pregnancy and breastfeeding has not been established. Hence, it should be used with caution in pregnant and breastfeeding women. 
• Drug interactions: frovatriptan should not be used in combination with other triptans or ergot alkaloids due to the risk of serotonin syndrome. It should also be used with caution in patients taking selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), as it can increase the risk of serotonin syndrome.

Comorbidities: 

• Cardiovascular disease: frovatriptan can cause constriction of blood vessels, which may lead to an increase in blood pressure. Patients with a history of cardiovascular diseases, such as angina, heart attack, stroke, or peripheral vascular disease, should be monitored closely when using frovatriptan. 
• Liver disease: frovatriptan is metabolized in the liver, so patients with liver disease may have a slower elimination of the drug. Close monitoring of these patients may be required to prevent potential toxicity. 
• Renal impairment: frovatriptan is excreted through the kidneys, so patients with renal impairment may have a slower elimination of the drug. Close monitoring of these patients may be required to prevent potential toxicity. 
• Hemiplegic or basilar migraine: frovatriptan is not recommended for patients with a history of hemiplegic or basilar migraine, as it may exacerbate these conditions. 
• Seizure disorders: frovatriptan may lower the seizure threshold and may not be appropriate for patients with a history of seizure disorders. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category C 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

frovatriptan is a selective serotonin receptor agonist belonging to the triptan class of drugs. It is a 5-HT1B/1D receptor agonist that exerts its action by binding to and stimulating these receptors, resulting in vasoconstriction of dilated cranial blood vessels, and inhibiting the release of inflammatory neuropeptides. 

frovatriptan also has some affinity for 5-HT7 receptors, which are thought to be involved in the regulation of circadian rhythm and cognitive processes, although the clinical significance of this is not yet fully understood. Overall, frovatriptan’s pharmacological effects contribute to its efficacy in treating migraine headaches.  

Pharmacodynamics: 

frovatriptan is a selective serotonin receptor agonist that acts specifically on the 5-HT1B/1D subtype. Binding to these receptors causes vasoconstriction of the dilated blood vessels in the brain, which reduces the inflammation and pain associated with migraines. Additionally, frovatriptan inhibits the release of calcitonin gene-related peptide (CGRP), which is involved in the development of migraine symptoms such as pain, nausea, and vomiting. 

The onset of action of frovatriptan is slow, with a peak effect seen between 2 to 4 hours after oral administration. The duration of action is long, with a half-life of approximately 26 hours, which makes it useful in preventing recurrent migraines. 

frovatriptan also exhibits high selectivity for the serotonin receptor subtype, with little or no affinity for other receptors. This selectivity reduces the potential for adverse effects, particularly cardiovascular events.  

Pharmacokinetics: 

Absorption 

frovatriptan is well absorbed after oral administration, with a bioavailability of approximately 25%. Food may decrease the rate of absorption but not the extent of absorption.  

Distribution 

frovatriptan has a high plasma protein binding of approximately 85% and has a volume of distribution of 4.2 L/kg.  

Metabolism 

frovatriptan undergoes extensive first-pass metabolism in the liver by the cytochrome P450 system, primarily CYP1A2 and, to a lesser extent, by CYP2D6. The major metabolite, accounting for 40% of the administered dose, is an indole acetic acid derivative, which is further metabolized to glucuronide and sulfate conjugates.  

Elimination and excretion 

frovatriptan and its metabolites are eliminated in the urine and feces, with 27% of the administered dose excreted in urine as an unchanged drug and 20% in feces. The elimination half-life of frovatriptan is approximately 26 hours. 

frovatriptan is eliminated by the kidney, and dose reduction is recommended in patients with moderate to severe renal impairment. 

Adminstartion

Administration: 

frovatriptan is available in oral tablet form and is usually taken with or without food. The usual recommended dose is 2.5 mg once daily, which can be increased to 5 mg if needed and tolerated, with at least a 2-hour interval between doses. The maximum daily dose should not exceed 7.5 mg within any 24-hour period. 

frovatriptan should be taken at the first sign of a migraine headache. It is not intended for the prevention of migraine headaches, and it should not be used to treat other types of headaches. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: frovatriptan 

Pronounced: (fro-va-trip-tin)  

Why do we use frovatriptan? 

frovatriptan is a medication used for the acute treatment of migraine headaches in adults. It belongs to the class called triptans, which acts by narrowing blood vessels in the brain and blocking certain natural substances release that causes pain, nausea, and other symptoms associated with migraines.

frovatriptan is specifically indicated for the treatment of menstrual migraine, which is a type of migraine that occurs around the time of a woman’s menstrual period. It can also be used to treat other types of migraines, such as those without aura, with or without a history of aura. However, it is not recommended for the prevention of migraines.