Continuing Education Activity

Almotriptan is a medication used in the management and treatment of acute migraines. It is in the triptan 5-HT class of drugs. This activity reviews the indications, action, and contraindications for almotriptan as a valuable agent in treating and managing acute migraines. This activity will highlight the mechanism of action, adverse effects, and other vital factors such as dosing, pharmacodynamics, pharmacokinetics, monitoring, and relevant interactions pertinent for interprofessional team members in the treatment and care of patients with acute migraines and related conditions.

Objectives:

• Identify the indications for almotriptan use.
• Summarize the risks associated with almotriptan use.
• Describe the most common adverse effects of almotriptan use.
• Explain the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients treated with almotriptan.

Indications

Almotriptan is the first FDA-approved drug used to treat migraine headaches in adults with or without an aura.[1] The drug is also useful in adolescents with a history of a migraine that, when left untreated, lasts 4 hours or longer. Certain triptan medications such as almotriptan and rizatriptan have also been shown to be effective and safe for managing acute migraines and other benign headaches in the pediatric population (less than 18 years of age).[2] 

Almotriptan has approval for use as monotherapy and in conjunction with migraine-abortive medications such as non-steroidal anti-inflammatory drugs (e.g., aceclofenac).[3] It is usually taken by mouth as a tablet.[4] Almotriptan is a white, coated circular tablet and requires a prescription from a registered physician in the United States.[5] 

A randomized, double-blind study by Pascual J. et al. examined the therapeutic efficacy and side effect profile of almotriptan. It was given as a single dose of 6.25 mg or 12.5 mg, and it was compared with placebo in patients with three consecutive migraine episodes of moderate to severe presentation. Seven hundred twenty-two patients completed the study out of 1013 initially enrolled. Almotriptan was found to be superior to placebo in reducing the migraine pain from moderate-severe to mild-no pain at 2 hours after the dose, i.e., 60% (6.25 mg) and 70% (12.5 mg) vs. 38% (placebo). There appeared to be no clinically significant differences in side effects between the almotriptan-treated patients compared with placebo. The study recommends a dose of 12.5 mg to treat migraines because the risk/benefit ratio is optimal at this dose.[6]

A randomized double-blinded study by Dalof C. et al. examined the therapeutic efficacy and side effect profile of almotriptan. It was given as a single dose of 2 mg, 6.25 mg, 12.5 mg, or 25 mg, and it was compared with placebo in patients with moderate to severe migraine pain intensity. Seven hundred forty-two patients completed the study out of 903 initially enrolled. Almotriptan was found to be superior to placebo in reducing the migraine pain at doses above 2 mg at 2 hours after dose, i.e., 30% (2 mg), 56.3% (6.25 mg), 58.5% (12.5 mg), 66.5% (25 mg) vs. 32.5% (placebo). There appeared to be no clinically important differences in side effects between the almotriptan-treated patients at doses of 2 mg, 6.25 mg, and 12.5 mg compared with placebo. The study recommends a dose of 12.5 mg to treat migraines because the risk/benefit ratio is optimal at this dose, and the 6.25 mg dose demonstrated a minimum effective dose.[7]

A double-blind comparison study by Spierings L. et al. examined the therapeutic efficacy (24-hour abortive treatment) and side effect profiles of almotriptan vs. sumatriptan which is an older anti-migraine medication commonly used in comparison studies. Almotriptan was given at a dose of 12.5 mg, and sumatriptan was given at a dose of 50 mg in patients with moderate to severe migraines. The oral capsules of each medication appeared identical to ensure blinding of patients and investigators. One thousand one hundred seventy-three patients received either almotriptan (591) or sumatriptan (582). Almotriptan was found to be similar to sumatriptan in reducing migraine pain 58.0% vs. 57.3%, respectively. Rescue medications were taken by patients in the almotriptan treatment arm 36.7% and 33.2% in the sumatriptan treatment arm. Moderate to severe intensity migraines returned in almotriptan and sumatriptan-treated patients 27.4% vs. 24.0%, respectively. Side effects appeared in 15.2 % of almotriptan-treated patients and 19.4% sumatriptan-treated patients. A potentially significant side effect of chest pain occurred at a higher rate in sumatriptan-treated patients vs. almotriptan-treated patients, 2.2% vs. 0.3%, respectively. The study concluded that almotriptan was similar to sumatriptan in therapeutic efficacy and side effect profiles.[8]

In pregnant women with migraines or headaches, triptan use is less frequent, whereas drugs like metoclopramide and acetaminophen are more common choices for migraines due to their effectiveness and safety.[9] Triptans have also been quite effective in treating menstrual migraines in premenopausal women. Various studies have shown that rizatriptan has proven to be the most beneficial in treating acute menstrual migraines in females among triptan drugs.[10] A randomized, placebo-controlled study showed that rizatriptan provided pain relief between 2 to 24 hours with an efficacy of 63 percent when compared to other triptans.[10] 

Mechanism of Action

Almotriptan is a selective serotonin agonist on the 5-HT1B and 5-HT1D receptors in the cranial arteries. Activation of the 5HT receptors is associated with reducing neurogenic inflammation, which researchers hypothesize to be involved in the migraine relief process.

Almotriptan works by narrowing the blood vessels in the brain, thereby reducing the cerebral blood flow stopping the transmission of pain signals to the brain center.[11] The drug has a relatively short half-life of 3 hours, and the oral bioavailability was found to be 69.1%.[12] Almotriptan is excreted in the urine and metabolized predominantly by the cytochrome CYP450 system.[12] Compared with earlier generation triptans such as sumatriptan, almotriptan has a higher oral bioavailability and a shorter plasma half-life.[11]

Administration

The recommended oral dose of almotriptan is 12.5 mg to treat acute migraine attacks in adults and adolescents effectively.[12] The dose may be repeated after two hours if a headache returns. It is recommended not to administer more than two doses or more than 25 mg/day. Studies have also shown that almotriptan has a synergistic effect when combined with aceclofenac 100 mg to treat an acute migraine attack.[3] 

Food intake has not demonstrated any effect on the absorption of almotriptan; therefore, its dosing can be without regard to food intake.[12] Dosing adjustment is recommended in patients with renal insufficiency. Dosing adjustment is necessary when the drug is used with cytochrome P450 inducers (e.g., phenytoin, phenobarbital) and cytochrome P450 inhibitors (e.g., certain antimicrobials, grapefruit juice, ketoconazole, protease inhibitors). 

Adverse Effects

The common adverse effects of almotriptan are drowsiness, dizziness, headache, nausea, vomiting, chest pain, and fatigue.[13] The drug is associated with a similar incidence of nausea/vomiting compared to other classes of triptans (e.g., sumatriptan). However, it shows a decreased incidence of the other common adverse effects listed above, especially when compared to first-generation triptans.[11][13] 

Almotriptan binds to 5HT1B receptors, which are present in the coronary arteries; thus, the administration may result in coronary artery narrowing or spasms, leading to potential coronary artery vasospasm or myocardial infarction.[14] Some rare side effects of almotriptan include pulmonary vasoconstriction, serotonin syndrome, inhibition of trigeminal nerves.[15][16]

Contraindications

Almotriptan is contraindicated in patients with renal dysfunction or insufficiency and the elderly due to a physiological decrease in renal function and renal clearance with advanced age.[12] 

Minor clearance of almotriptan occurs through the CYP450 system (specifically, CYP3A4); therefore, the clinician should avoid other drugs metabolized through this pathway because they may decrease almotriptan clearance. These drugs include but are not limited to verapamil, nifedipine, losartan, cyclosporine, and moclobemide.[12] It is reasonable to assume that patients with decreased activity of this enzyme should be cautious in dosing the drug.

Contraindications to almotriptan also include patients with underlying cardiovascular disease due to the presence of 5HT1B receptors on the coronary arteries. Almotriptan potentially binds to such receptors resulting in further narrowing or spasm of the arteries.[14] Patients with hypersensitivity to almotriptan should not use the drug, nor should patients with a history of a hemiplegic or basilar migraine or a heart condition. Moreover, this medication is not for use in patients with cerebrovascular syndromes, peripheral vascular disease, or high blood pressure. Caution is necessary if dosing almotriptan within 24 hours of using a serotonin agonist or an ergotamine class medication due to the vasoconstrictive effects of both drugs.[16] 

Monitoring

Patients taking almotriptan should require monitoring for the presence of side effects and response to therapy. Kidney function should be monitored when taking the drug as renal clearance may affect the overall drug clearance from the body, causing toxicity. Regular monitoring of the blood pressure should occur at each clinical visit due to the narrowing effect of the 5-HT1B receptors on the blood vessels and assess the effectiveness of the drug.[16] 

Toxicity

There are no associated toxicities with almotriptan due to the limited data, although studies demonstrate increased preterm birth rates in pregnant women that received triptans for migraine relief.[17]

An analysis of several case reports of patients undergoing dual triptan-SSRI/SNRI, e.g., fluoxetine and venlafaxine, therapy or triptan monotherapy, suggested adding triptans to SSRI/SNRI therapy does not necessarily increase patients' risk of developing serotonin syndrome. However, providers should remain cautious and vigilant of the symptoms.[18]

Enhancing Healthcare Team Outcomes

Managing the administration of almotriptan in patients with acute migraines requires an interprofessional team of healthcare professionals that include a neurologist, primary care physician, nephrologist in the case of a compromised renal function, psychiatrist, specialty-trained nursing staff, and pharmacist for appropriate dosing and safety precautions, all working collaboratively to ensure optimal patient outcomes. Nurses must be ready to inform the prescriber regarding any potential adverse events from the medication and monitor whether almotriptan provides adequate migraine pain relief. The pharmacist must look into possible drug-drug interactions, verify dosing, counsel the patient on proper administration, and answer patient questions regarding the safe use of the drug. A robust support system consisting of the patients' family and friends may also contribute to successful health outcomes.

Consistent patient follow-up and adherence to appointment times are essential for properly monitoring vital signs and managing any adverse effects. Moreover, it is also necessary for assessing drug effectiveness. This type of interprofessional team effort is essential to optimize therapy with almotriptan so the patient can achieve the best outcomes. [Level 5]