Frovatriptan Succinate

Pronunciation: froe-va-TRIP-tan
Class: Serotonin 5-HT 1 receptor agonist

Trade Names

Frova
- Tablets 2.5 mg (as base)

Pharmacology

Selectively agonizes 5-hydroxy-tryptamine 1 (5-HT 1B/1D ) receptor, inhibiting excessive dilation of extracerebral and intracranial arteries in migraine.

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

Pharmacokinetics

Absorption

T max is about 2 to 4 h. Bioavailability is about 20% in men and about 30% in women.

Distribution

Protein binding is about 15%. Mean Vd ss is 4.2 L/kg in men and 3 L/kg in women.

Metabolism

CYP-450 1A2 is the major enzyme involved.

Elimination

About 32% is excreted in urine and 62% in feces. Mean Cl is 220 mL/min in men and 130 mL/min in women. Mean t 1/ 2 is about 26 h.

Special Populations

Hepatic Function Impairment

In mild (Child-Pugh class 5 to 6) to moderate (Child-Pugh class 7 to 9) hepatic function impairment, AUC increased 2 times that of healthy subjects.

Elderly

AUC was 1.5- to 2-fold higher in elderly subjects.

Indications and Usage

Acute treatment of migraine attacks with or without aura in adults.

Contraindications

Patients with ischemic heart disease (eg, angina pectoris, history of MI, documented silent ischemia); history of symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal variant angina or other underlying CV disease; cerebrovascular syndromes (eg, strokes of any type, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; hemiplegic or basilar migraine; within 24 h of another 5-HT 1 agonist, and ergotamine-containing or ergot-type medication (eg, dihydroergotamine); hypersensitive to frovatriptan or any inactive ingredient in the tablet.

Dosage and Administration

Adults

PO 2.5 mg with fluids; if headache recurs after initial relief, a second 2.5-mg tablet may be taken provided the interval is at least 2 h between doses (max, three 2.5 mg tablets/day).

General Advice

  • Administer at onset of migraine symptoms.
  • Administer without regard to meals.

Storage/Stability

Store at ambient room temperature (59° to 86°F) protected from light and moisture.

Drug Interactions

Contraceptives, oral and propranolol

May increase frovatriptan plasma concentrations.

Ergotamine-containing or ergot-type drugs (eg, methysergide)

May reduce frovatriptan plasma levels; additive prolonged vasospastic reactions may occur.

Other 5-HT 1 agonists (eg, sumatriptan)

Contraindicated within 24 h of frovatriptan administration.

SSRIs (eg, fluoxetine)

May cause weakness, hyperreflexia, and incoordination when given concurrently.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Flushing (4%); palpitations (at least 1%).

CNS

Dizziness (8%); fatigue (5%); headache, paresthesia (4%); dysesthesia, hypoesthesia, insomnia, anxiety (at least 1%).

Dermatologic

Increased sweating (at least 1%).

EENT

Abnormal vision, tinnitus (at least 1%).

GI

Dry mouth (3%); dyspepsia (2%); vomiting, abdominal pain, diarrhea (at least 1%).

Musculoskeletal

Skeletal pain (3%).

Respiratory

Sinusitis, rhinitis (at least 1%).

Miscellaneous

Hot or cold sensation (3%); chest pain (2%); pain (at least 1%).

Precautions

Monitor

Assess pain location, intensity, duration, and associated symptoms of migraine attack and response to treatment.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

CV events

Serious cardiac events, including acute MI, life-threatening cardiac arrhythmias, and death may occur. Ensure that patients with potential for coronary artery disease (CAD), including postmenopausal women and men older than 40 yr of age, and patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, obesity, diabetes, smokers, family history) undergo a CV evaluation before initiating therapy.

Cerebrovascular events

Stroke, cerebral hemorrhage, subarachnoid hemorrhage, and other cerebrovascular events may occur.

First dose

Administer first dose in physician's office or other adequately staffed medical facility to patient with potential for CAD whose CV evaluation provided clinical evidence that patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying CV disease. Consider obtaining an ECG during the interval immediately following administration of the first dose of medication to patient with potential for CAD.

Vasospastic events

Vasospastic-related reactions (eg, peripheral vascular ischemia, colonic ischemia) may occur.

Patient Information

  • Advise patient to read the patient information leaflet before starting therapy and again with each refill.
  • Explain that drug is to be used only during migraine and does not prevent or reduce the number of attacks. Emphasize that drug is used only to treat actual migraine attack and should not be used to prevent migraine headaches or treat headaches caused by other conditions.
  • Advise patient that drug is to be taken as soon as symptoms of migraine appear. A second dose may be taken if symptoms return, but no sooner than 2 h following the first dose. For a given attack, if there is no response to the first tablet, do not take a second tablet without first consulting health care provider. Do not take more than 3 tablets in any 24-h period.
  • Advise patient that safety of treating more than 4 headaches in a 30-day period has not been established and to inform health care provider if headaches are occurring more frequently.
  • Advise patient to immediately notify health care provider if any of the following occur after taking a dose of frovatriptan: severe chest pain or chest pain that does not go away; sudden and/or severe stomach pain; shortness of breath; wheezing; swelling of eyelids, face, or lips.
  • Advise patient that if tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw occur when using sumatriptan, to discuss these symptoms with health care provider before using again.
  • Advise patient to notify health care provider if feelings of tingling, heat, flushing, tiredness, dizziness, heaviness, or pressure occur after treatment.
  • Advise patient that drug may cause fatigue or dizziness and to use caution while driving or performing other activities requiring mental alertness.
  • Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
  • Instruct patient to continue to take migraine prophylactic medications daily as directed.
  • Advise patient not currently taking a migraine prophylactic drug to discuss the use of such drugs with health care provider.

Copyright © 2009 Wolters Kluwer Health.

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