Frovatriptan

Frovatriptan is a prescription drug used for the treatment of migraine attacks. It belongs to a family of anti-migraine drugs called triptans. Other triptans include sumatriptan (Imitrex, Imigran) and zolmitriptan (Zomig). These drugs mimic the action of the neurotransmitter serotonin. Neurotransmitters carry signals from one neuron to another, or from a neuron to a muscle. They are thought to alleviate migraine symptoms by constricting blood vessels in the brain. The Food and Drug Administration approved frovatriptan in November 2001. Frovatriptan is marketed as Frova by Endo Pharmaceuticals in the United States and by Menarini in Europe.

Uses
Frovatriptan is used to treat migraine headaches, with or without aura, in adults. It is often used to treat headaches associated with menstruation.

How is Taken
Frovatriptan is available in 2.5 mg oral tablets. The recommended dose is a single 2.5 mg tablet taken with fluids at the onset of a headache. If the headache recurs after the first dose, a second tablet may be taken at least two hours after the initial dose. The total daily dose should not exceed three tablets.

How Works
The pain of migraine headaches is thought to be caused by widening of blood vessels and the release of inflammatory chemicals around nerve cells. The neurotransmitter serotonin, also called 5—hydroxytryptamine, constricts blood vessels after activating serotonin receptors on the surface of blood vessel walls. Like other triptans, frovatriptan binds to and activates these same serotonin receptors. The result is constriction of blood vessels, which makes them leak less, and the reduction of inflammation.

How the Body Affects
Peak circulating levels of frovatriptan are achieved approximately 2–4 hours after administration. Frovatriptan is primarily metabolized in the liver by the enzyme CYP1A2. About 60% of frovatriptan is excreted in the feces and about 30% is excreted in the urine.

Side Effects
The most common side effects of frovatriptan, which occur in more than 2% of treated people, are the following:


 * Dizziness
 * Headache
 * tingling sensations
 * Dry mouth
 * indigestion
 * Fatigue
 * Hot or cold sensations
 * Chest pain
 * Skeletal pain
 * Flushing

Risks and Precautions
Triptans like frovatriptan can cause spasms in the arteries feeding the heart. Risk of serious complications due to this coronary vasospasm are highest in the following conditions:


 * coronary artery disease
 * history of strokes
 * peripheral vascular disease
 * uncontrolled high blood pressure

Drug Interactions
Ergot-containing drugs have been reported to cause prolonged spasms in blood vessels, including coronary arteries. Thus, concomitant use of frovatriptan with these drugs increases the risk of coronary events. This risk is reduced substantially if frovatriptan is not taken within 24 hours of taking an ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide). Other triptans also carry the risk of these vasospasms. Again, this risk is minimal if frovatriptan is not taken within 24 hours of taking another triptan.

Because frovatriptan acts like serotonin, it could interact with any drug that stimulates the serotonergic system. The selective serotonin reuptake inhibitor (SSRI) antidepressants work by elevating levels of serotonin in the brain. These drugs, which include fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft), have been reported to cause weakness and incoordination when coadministered with triptans. In addition, the serotonin-norepinephrine reuptake inhibitors (SNRIs like venlafaxin (Effexor)) elevate serotonin levels and carry a similar risk when administered with frovatriptan. Drugs that inhibit the enzyme monoamine oxidase (MAO inhibitors) also increase serotonin levels.

Clinical Trials
Data from five trials were pooled and analyzed to determine the effectiveness of frovatriptan in the prevention of pain associated with migraine. Patients taking frovatriptan, compared to those taking placebo, were at least two-times less likely to have pain two or four hours after taking the drug. Frovatriptan also reduced pain severity more than did placebo and reduced the risk of a headache recurrence within 24 hours by 26%. A previous analysis of three trials also found that frovatriptan was a consistently effective acute treatment for migraine attacks.