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Medication Safety Issues
International issues:
Allegro® [Germany] may be confused with Allegra® which is a brand name for fexofenadine in the U.S.
Allegro®: Brand name for fluticasone in Israel
Pronunciation
(froe va TRIP tan)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Acute treatment of migraine with or without aura
Pregnancy Risk Factor
C
Pregnancy Considerations
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
Canadian labeling: Additional contraindications (not in U.S. labeling): Cardiac arrhythmias, valvular heart disease, congenital heart disease, atherosclerotic disease; management of ophthalmoplegic migraine; severe hepatic impairment
Warnings/Precautions
Concerns related to adverse effects:
• Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT1 agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses.
• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration.
• Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension.
• Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist administration.
Disease-related concerns:
• Coronary artery disease: Should not be given to patients who have risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation “is satisfactory”, first dose should be given in the healthcare provider's office. Periodic evaluation of cardiovascular status should be done in all patients.
• Neurologic disease: Use with caution in patients with epilepsy and structural brain lesions; may lower seizure threshold.
Concurrent drug therapy issues:
• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (eg, SSRIs/SNRIs or triptans) or agents which reduce frovatriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <18 years of age.
Other warnings/precautions:
• Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis or for the treatment of cluster headaches. If a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered; rule out underlying neurologic disease in patients with atypical headache, migraine (with no prior history of migraine) or inadequate clinical response to initial dosing.
Adverse Reactions
1% to 10%:
Cardiovascular: Flushing (4%), chest pain (2%), palpitation (1%)
Central nervous system: Dizziness (8%), fatigue (5%), headache (4%), hot or cold sensation (3%), somnolence (?2%), anxiety (1%), dysesthesia (1%), hypoesthesia (1%), insomnia (1%), pain (1%)
Gastrointestinal: Xerostomia (3%), nausea (?2%), dyspepsia (2%), abdominal pain (1%), diarrhea (1%), vomiting (1%)
Neuromuscular & skeletal: Paresthesia (4%), skeletal pain (3%)
Ocular: Vision abnormal (1%)
Otic: Tinnitus (1%)
Respiratory: Rhinitis (1%), sinusitis (1%)
Miscellaneous: Diaphoresis (1%)
<1%, postmarketing, and/or case reports: Abnormal dreaming, abnormal gait, abnormal lacrimation, abnormal reflexes, abnormal urine, agitation, amnesia, anorexia, arthralgia, arthrosis, ataxia, back pain, bowel changes, bradycardia, bullous eruption, cheilitis, concentration impaired, confusion, conjunctivitis, constipation, dehydration, depersonalization, depression, dysphagia, dyspnea, earache, ECG changes, emotional lability, epistaxis, eructation, esophagospasm, euphoria, eye pain, fever, flatulence, gastroesophageal reflux, hiccup, hot flushes, hyperacusis, hyperesthesia, hypertonia, hyperventilation, hypocalcemia, hypoglycemia, hypotonia, involuntary muscle contractions, laryngitis, leg cramps/pain, malaise, micturition, mouth edema, muscle weakness, myalgia, nervousness, nocturia, peptic ulcer, personality disorder, pharyngitis, polyuria, pruritus, purpura, renal pain, rigors, saliva increased, salivary gland pain, seizure, speech disorder, stomatitis, syncope, tachycardia, taste perversion, thirst, tongue paralysis, toothache, tremor, urinary frequency, vertigo, weakness
Metabolism/Transport Effects
Substrate of CYP1A2 (minor)
Drug Interactions
Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: Food does not affect frovatriptan bioavailability.
Storage
Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Mechanism of Action
Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes 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: Male: ~20%; Female: ~30%
Half-life elimination: ~26 hours
Time to peak: 2-4 hours
Excretion: Feces (62%); urine (32%; <10% as unchanged drug)
Dosage
Oral: Adults: Migraine:
U.S. labeling: 2.5 mg; if headache recurs, a second dose may be given if first dose provided relief and at least 2 hours have elapsed since the first dose (maximum daily dose: 7.5 mg)
Canadian labeling: 2.5 mg; if headache recurs, a second dose may be given if first dose provided relief and at least 4 hours have elapsed since the first dose (maximum daily dose: 5 mg)
Note: The safety of treating more than 4 migraines/month has not been established.
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 (has not been studied in severe impairment).
Canadian labeling (not in U.S. labeling): Use is contraindicated in severe hepatic impairment.
Administration: Oral
Administer with fluids.
Patient Education
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, feeling of tingling in extremities, 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.
Geriatric Considerations
Migraine headaches occur infrequently in elderly; however, since elderly often have cardiovascular disease, careful evaluation of the use of 5-HT agonists is needed to avoid complications with the use of these agents. The pharmacokinetic disposition of these agents is similar to that seen in younger adults.
Cardiovascular Considerations
Coronary vasospasm has been associated with 5-HT1B/1D agonists. These agents are contraindicated in patients with documented ischemic or vasospastic coronary artery disease. Patients with risk factors for CAD may receive these agents, provided a cardiovascular evaluation yields satisfactory evidence that the patient is free of cardiovascular disease. In patients with risk factors for CAD, administration of the initial dose in a medically staffed/equipped facility (ie, physician's office) is recommended. In addition, ECG monitoring after the initial dose should be considered. Patients who acquire risk factors for CAD, or long-term users of agents from this class of medications, should undergo periodic cardiovascular evaluation.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking (eg, ergot derivatives). Cardiovascular status should be evaluated prior to initiating medication and periodically thereafter. Assess effectiveness and adverse response. Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Frova®: 2.5 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Frova)
2.5 mg (9): $209.82
References
Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.
Rapoport A, Ryan R, Goldstein J, et al, “Dose Range-Finding Studies With Frovatriptan in the Acute Treatment of Migraine,” Headache, 2002, 42(Suppl 2):74-83.
Ryan R, Geraud G, Goldstein J, et al, “Clinical Efficacy of Frovatriptan: Placebo-Controlled Studies,” Headache, 2002, 42(Suppl 2):84-92.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2009
Content last modified August 2009
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