Frovatriptan

Pronunciation

(froe va TRIP tan)

U.S. Brand Names

Frova®

Synonyms

Frovatriptan Succinate

Generic Available

No

Use

Acute treatment of migraine with or without aura in adults

Pregnancy Risk Factor

C

Pregnancy Implications

There are no adequate and well-controlled studies using frovatriptan in pregnant women. Use only if potential benefit to the mother outweighs the potential risk to the fetus.

Lactation

Excretion in breast milk unknown/use caution

Contraindications

Hypersensitivity to frovatriptan or any component of the formulation; patients with ischemic heart disease or signs or symptoms of ischemic heart disease (including Prinzmetal's angina, angina pectoris, myocardial infarction, silent myocardial ischemia); cerebrovascular syndromes (including strokes, transient ischemic attacks); peripheral vascular syndromes (including ischemic bowel disease); uncontrolled hypertension; use within 24 hours of ergotamine derivatives; use within 24 hours of another 5-HT1 agonist; management of hemiplegic or basilar migraine; prophylactic treatment of migraine; severe hepatic impairment

Warnings/Precautions

Not intended for migraine prophylaxis, or treatment of cluster headaches, hemiplegic or basilar migraines. Cardiac, cerebral/subarachnoid hemorrhage, and stroke have been reported with 5-HT1 agonist administration. May cause vasospastic reactions resulting in colonic, peripheral, or coronary ischemia. Do not give to patients with risk factors for CAD until a cardiovascular evaluation has been performed; if evaluation is satisfactory, the healthcare provider should administer the first dose and cardiovascular status should be periodically evaluated. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients using other 5-HT1D agonists with and without a history of hypertension. Use with caution in patients with history of seizure disorder. Safety and efficacy in pediatric patients have not been established.

Adverse Reactions

1% to 10%:

Cardiovascular: Chest pain (2%), flushing (4%), palpitation (1%)

Central nervous system: Dizziness (8%), fatigue (5%), headache (4%), hot or cold sensation (3%), anxiety (1%), dysesthesia (1%), hypoesthesia (1%), insomnia (1%), pain (1%)

Gastrointestinal: Hyposalivation (3%), dyspepsia (2%), abdominal pain (1%), diarrhea (1%), vomiting (1%)

Neuromuscular & skeletal: Paresthesia (4%), skeletal pain (3%)

Ocular: Visual abnormalities (1%)

Otic: Tinnitus (1%)

Respiratory: Rhinitis (1%), sinusitis (1%)

Miscellaneous: Diaphoresis (1%)

<1%: Abnormal dreaming, abnormal gait, abnormal lacrimation, abnormal reflexes, abnormal urine, agitation, amnesia, arthralgia, arthrosis, ataxia, back pain, bradycardia, bullous eruption, cheilitis, confusion, conjunctivitis, constipation, dehydration, depersonalization, depression, dysphagia, dyspnea, ear ache, ECG changes, emotional lability, epistaxis, eructation, esophagospasm, euphoria, eye pain, fever, gastroesophageal reflux, hiccup, hot flushes, hyperacusis, hyperesthesia, hypertonia, hyperventilation, hypocalcemia, hypoglycemia, hypotonia, impaired concentration, involuntary muscle contractions, laryngitis, leg cramps, malaise, micturition, muscle weakness, myalgia, nervousness, nocturia, peptic ulcer, personality disorder, pharyngitis, polyuria, pruritus, purpura, renal pain, rigors, saliva increased, salivary gland pain, speech disorder, stomatitis, syncope, tachycardia, taste perversion, thirst, tongue paralysis, toothache, tremor, unspecified pain, urinary frequency, vertigo, weakness

Overdosage/Toxicology

Single oral doses of up to 100 mg have been reported without adverse effects. Treatment of overdose should be supportive and symptomatic. Monitor for at least 48 hours or until signs and symptoms subside. It is not known if hemodialysis or peritoneal dialysis is effective.

Drug Interactions

Substrate of CYP1A2 (minor)

Ergot derivatives: Ergot derivatives may cause prolonged vasospastic reactions, creating additive toxicity with frovatriptan. Do not use within 24 hours of each other.

Estrogens (oral contraceptives): Estradiol may increase serum concentrations of frovatriptan

Propranolol: Propranolol may increase serum concentrations of frovatriptan

Selective serotonin reuptake inhibitors (SSRIs): Frovatriptan may increase SSRI toxicity (eg, weakness, hyper-reflexia, incoordination)

Serotonin agonists: May exhibit additive toxicity with other serotonin agonists (eg, antidepressants, dextromethorphan, tramadol), leading to serotonin syndrome.

Ethanol/Nutrition/Herb Interactions

Food: Food does not affect frovatriptan bioavailability.

Stability

Store at room temperature of 25°C (77°F); protect from moisture and light.

Mechanism of Action

Selective agonist for serotonin (5-HT1B and 5-HT1D receptor) in cranial arteries to cause vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine.

Pharmacodynamics/Kinetics

Distribution: Male: 4.2 L/kg; Female: 3.0 L/kg

Protein binding: 15%

Metabolism: Primarily hepatic via CYP1A2

Bioavailability: 20% to 30%

Half-life elimination: 26 hours

Time to peak: 2-4 hours

Excretion: Feces (62%); urine (32%)

Dosage

Oral: Adults: Migraine: 2.5 mg; if headache recurs, a second dose may be given if first dose provided some relief and at least 2 hours have elapsed since the first dose (maximum daily dose: 7.5 mg)

Dosage adjustment in renal impairment: No adjustment necessary

Dosage adjustment in hepatic impairment: No adjustment necessary in mild to moderate hepatic impairment; use with caution in severe impairment

Administration

Administer with fluids.

Patient Education

Inform prescriber of all prescriptions (including oral contraceptives), OTC medications, or herbal products you are taking, and any allergies you have. This drug is to be used to reduce your migraine, not to prevent or reduce the number of attacks. Follow exact instructions for use. Do not take within 24 hours of any other migraine medication without first consulting prescriber. If first dose brings relief, a second dose may be taken anytime after 2 hours if migraine returns. Do not take more than three tablets (7.5 mg) in 24 hours without consulting prescriber. May cause dizziness, fatigue, insomnia, or drowsiness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth (frequent mouth care and sucking on lozenges may help); skin flushing or hot flashes (cool clothes or a cool environment may help); or mild abdominal discomfort or vomiting (small, frequent meals, good mouth care, chewing gum, or sucking lozenges may help). Report immediately any chest pain, palpitations, or irregular heartbeat; severe dizziness, acute headache, stiff or painful neck, facial swelling, muscle weakness or pain, changes in mental acuity, blurred vision, eye pain, or ringing in ears; changes in urinary pattern; respiratory difficulty; or other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Dosage Forms

Tablet, as base: 2.5 mg

International Brand Names

Allegro® (DE); Eumitan® (AT); Frovex® (IE); Menamig® (CH); Migard® (GB)