Almotritan

Almotriptan is a drug used to treat migraines in adults. Almotriptan is a member of the triptan family. Triptans are migraine medications that activate serotonin receptors in the brain. Activation of these receptors reduces inflammation and fluid accumulation around blood vessels in the brain.

Other Names
Almotriptan is sold under the names Axert and Almogran.

Uses
Almotriptan is used for the short term treatment of most types of migraine attacks, with or without aura, in adults. It is not used to prevent migraines, or to decrease the number of migraine attacks.

How Almotriptan is Taken
Almotriptan is available in tablets of 6.25 mg and 12.5 mg. One tablet of either dose is taken at the onset of a migraine attack. If the headache returns, a second dose can be taken at least two hours after the initial dose. No more than two doses should be taken within a 24 hour period.

How Almotriptan Works
The pain of a migraine attack is thought to have two causes: dilated blood vessels and inflammation in the brain. The dilation (widening) of blood vessels in the brain causes them to leak blood and other fluids. Fluid accumulation can cause pain, but can also trigger inflammation, inflammation around sensory neurons, which are those that receive and send signals, including pain messages, as the result of a stimulus.

Serotonin, also called 5-hydroxytryptamine (5-HT), is a neurotransmitter. Neurotransmitters are chemicals that transmit signals from one neuron to another or from one neuron to a muscle. In the brain, serotonin constricts blood vessels and prevents transmission of painful stimuli. Specifically, almotriptan stimulates 5HT 1B/1D receptors, resulting in cerebral artery constriction and reduction of pro-inflammatory cytokine secretion. The migraine headache caused by cerebral vasodilation and inflammation is therefore alleviated.

Almotriptan is a triptan, and, like all triptans, mimics the action of serotonin in the brain. It activates several of the same receptors that serotonin does and elicits a similar physiologic response.

How the Body Affects Almotriptan
Almotriptan reaches a peak concentration in the blood one to three hours after administration. The half-life of almotriptan, the time needed for the concentration In the blood to be reduced by half, is 3–4 hours. Almotriptan is metabolized in the liver by enzymes called MAOs and CYPs.

Special populations
Liver impairment is expected to slow the clearance of almotriptan from the body and increase the concentration of the drug in the blood. Elevated levels of almotriptan could increase the risk of side effects. Use of low doses in people with impaired liver function reduces this risk.

Similarly, severe kidney impairment can reduce the clearance of almotriptan, and the manufacturer recommends that, in these cases, dosing should not exceed one 12.5 mg tablet in a 24 hour period.

Studies in healthy volunteers have shown that elimination of almotriptan is slower in the elderly (65 to 76 years of age) compared to adults aged 19 to 34 years. As a result, the half-life and plasma concentrations of almotriptan may be higher than that seen in younger adults. However, the elevations are not expected to influence the effectiveness or safety of almotriptan.

Gender and race (Caucasian vs. African American) do not influence the metabolism or elimination of almotriptan.

Side Effects
The most common side effects of almotriptan include the following:


 * Nausea


 * Sleepiness


 * Tingling or burning feeling


 * Headache


 * Dry mouth

Often the side effects are mild and of short duration.

Some more potentially serious side effects are severe pain, pressure or tightness in the chest or throat.

Complications
One of the greatest risks associated with the use of almotriptan is an interaction with other drugs that elevate levels of serotonin in the brain (See “Interactions”).

Because serotonin acts throughout the body, triptans can influence cardiovascular function throughout the body. Serious complications are rare, but the risk of adverse cardiovascular events is high in people who have, or have had, the following conditions:


 * Uncontrolled high blood pressure


 * Heart disease or a history of heart disease


 * Hemiplegic or basilar migraine


 * Stroke


 * Circulation problems to the arms, legs, and bowels

Rarely, people have a serious allergic reaction to almotriptan. This reaction could cause shortness of breath, wheeziness, heart throbbing, swelling of eyelids, face, or lips, or a skin rash, lumps or hives.

Interactions
Over-stimulation of the serotonergic system can occur if almotriptan is taken in combination with other drugs that enhance serotonin levels. Monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) all increase the activity of serotonin. Some examples of these drugs are listed below:


 * MAOIs: selegine, rasagiline (Azilect)


 * SSRIs: fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro), fluvoxamine (Luvox)


 * SNRIs: venlafaxine (Effexor)

The most dangerous consequence of high serotonin levels is the serotonin syndrome, which can be life-threatening. Some symptoms of the syndrome include restlessness, hallucinations, loss of coordination, fast heart beat, and increased body temperature. The syndrome is more likely to occur when starting or increasing the dose of almotriptan, the SSRI, SNRI, or MAO.

Other triptans and migraine medicines called ergot derivatives (which contain ergotamine, dihydroergotamine, or methylsergide) can potentiate the effects of almotriptan. Ergot derivatives can be taken safely at least 24 hours before or after taking almotriptan. Another triptan can be taken two hours after taking almotriptan, but dosing with more than any two triptans within a 24 hour period can be harmful.

The CYP3A4 enzyme partly metabolizes almotriptan. Therefore, drugs that inhibit the activity of CYP3A4 could elevate levels of almotriptan. The interaction is more likely with strong CYP3A4 inhibitors such as:


 * The antigungals ketoconazole (Nizoral) or itraconazole (Sporanox)


 * Nefazodone (Serzone)


 * Antibiotics like clarithromycin (Biaxin), erythromycin, or troleandomycin (TAO)


 * The antiHIV drugs ritonavir (Norvir) or nelfinavir (Viracept)

Overdose
Single, 200-mg doses of almotriptan have not been reported to have caused any significant adverse reactions.

History
The U.S. Food and Drug Administration approved almotriptan on May 7, 2001. Almotriptan was developed by Almirall Prodesfarma and is marketed in the United States and Canada by Ortho-McNeil under the brand name Axlert. It marketed as Almogran in Belgium, Finland, France, Germany, Italy, Portugal, Spain and the United Kingdom

Research

 * A multicenter trial determined the effectiveness of almotriptan in over 300 patients.[1] In the trial, the participants were instructed to take 12.5 mg within one hour of pain onset. Two hours after onset, 37% of patients given almotriptan had complete pain relief and 72% had some relief. At the same timepoint, 24% and 48% of patients given a placebo had complete pain relief and some pain relief, respectively.


 * A randomized double-blind, placebo-controlled study showed almotriptan to be a safe and effective treatment for acute migrane headache in adolescents. [2]


 * Another study showed almotriptan to be equally effective for menstrually-related and non-menstrually related migranes. [3]


 * The use of triptans, including almotriptan, were studied in pregnancy. The main side effect was an increase in preterm delivery. No teratogenicity was noted. [4]


 * The difference between early treatment of migranes with almotriptan, regardless of pain intensity, and treatment in response to pain intensity was studied. Time to treatment was a better predictor of headache duration and pain intensity was a better predictor of duration of pain relief. [5]

Clinical Trials
Information about a clinical trial evaluating the use of almotriptan with topiramate (an anticonvulsant medication) to detoxify and treat medication overuse headache is available at ClinicalTrials.gov: almotriptan trials