Continuing Education Activity

Almotriptan is a medication used in the management and treatment of acute migraines. The medication is in the triptan 5-HT class of drugs. Participating clinicians review the indications, actions, and contraindications for almotriptan as a valuable agent in treating and managing acute migraines.

This activity highlights the mechanism of action, adverse effects, and vital factors such as dosing, pharmacodynamics, pharmacokinetics, monitoring, and relevant interactions pertinent for interprofessional team members in treating and caring for patients with acute migraines and related conditions. The interprofessional team, ranging from primary care clinicians and emergency clinicians to specialists, benefit from guideline-specific practices.

Objectives:

• Identify the indications for almotriptan use.

• Differentiate between various migraine types and accurately diagnose those suitable for almotriptan intervention, considering factors such as aura, frequency, and associated symptoms.

• Implement evidence-based guidelines in the use of almotriptan for acute migraine attacks, including dosage adjustments and appropriate timing of administration.

• Collaborate with the interprofessional team to coordinate a comprehensive approach to migraine management, especially in cases requiring a multidisciplinary perspective.

Indications

Almotriptan is the first FDA-approved drug to treat migraine headaches in adults with or without an aura.[1] The drug is also beneficial 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, are effective and safe for managing acute migraines and 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 (eg, aceclofenac).[3] Oral formulations are the most common.[4] Almotriptan is a white, coated circular tablet and requires a prescription from a registered clinician 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. The drug was given as a single dose of 6.25 mg or 12.5 mg and compared with placebo in patients with 3 consecutive migraine episodes of moderate to severe presentation. Seven hundred twenty-two patients completed the study out of 1013 initially enrolled. Almotriptan was superior to placebo in reducing the migraine pain from moderate-severe to mild-no pain at 2 hours after the dose, ie, 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 the placebo. The study recommends a dose of 12.5 mg to treat migraines because the risk-to-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. The triptan was given as a single dose of 2 mg, 6.25 mg, 12.5 mg, or 25 mg, and it was compared with a 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 superior to placebo in reducing the migraine pain at doses above 2 mg at 2 hours after dose, ie, 30% (2 mg), 56.3% (6.25 mg), 58.5% (12.5 mg), 66.5% (25 mg) vs. 32.5% (placebo). There are no clinically significant 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-to-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, 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 similar to sumatriptan in reducing migraine pain by 58.0% vs. 57.3% respectively.

Patients in the almotriptan treatment arm took rescue medications at 36.7% and 33.2% in the sumatriptan treatment arm. Moderate to severe intensity migraines returned in almotriptan and sumatriptan-treated patients at 27.4% vs. 24.0%, respectively. Side effects appeared in 15.2% of almotriptan-treated patients and 19.4% of 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 common choices for migraines due to their effectiveness and safety.[9] Triptans are effective in treating menstrual migraines in premenopausal women. Various studies have shown that rizatriptan is the most beneficial triptan to treat acute menstrual migraines in females.[10] A randomized, placebo-controlled study showed that rizatriptan provided pain relief between 2 and 24 hours with an efficacy of 63% compared to other triptans.[10] 

There is limited data on the use of almotriptan during breastfeeding. The concentration of almotriptan in breast milk is low. Clinicians should consider alternative treatment because of a lack of data on safety.[11]

Almotriptan has been used for acute migraines for over 20 years with safety and efficacy.[12] The drug is also effective in treating menstrual migraines.

Triptans (sumatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan, rizatriptan, and frovatriptan) were studied in 186 randomized controlled trials (N = 101,276).[13] Triptans controlled pain at 2 hours and 1 day when compared to a placebo. Triptans were also a risk for mild and transient side effects.

Mechanism of Action

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.

Pharmacokinetics

Almotriptan narrows the brain's blood vessels, reduces cerebral blood flow, and reduces the transmission of pain signals to the brain.[14] 

Absorption

The drug has a relatively short half-life of 3 hours, and the oral bioavailability was 69.1%.[15] The currently available oral delivery system of almotriptan has limited bioavailability because of poor aqueous solubility. To improve the solubility of almotriptan, researchers have created a buccal delivery system for almotriptan, which was tested in a rabbit model.[16] The buccal delivery system demonstrated greater absorption when compared to the current oral delivery system

Distribution, Metabolism, Elimination

Almotriptan is excreted in the urine and metabolized predominantly by the cytochrome CYP450 system.[15] Compared with earlier generation triptans such as sumatriptan, almotriptan has a higher oral bioavailability and a shorter plasma half-life.[14]

Administration

Adult Dosage

The recommended oral dose of almotriptan is 12.5 mg to treat acute migraine attacks in adults and adolescents effectively.[15] The dose may be repeated after 2 hours if a headache returns. More than 2 doses or 25 mg/d is not recommended. 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 does not affect the absorption of almotriptan.[15] 

Renal Impairment

Dosing adjustment is recommended in patients with renal insufficiency.

Hepatic Impairment

Dosing adjustment is necessary when the drug is used with cytochrome P450 inducers (eg, phenytoin, phenobarbital) and cytochrome P450 inhibitors (eg, 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.[17] The drug is associated with a similar incidence of nausea or vomiting compared to other classes of triptans (eg, sumatriptan). However, it shows a decreased incidence of common adverse effects, especially compared to first-generation triptans.[14][17] 

Almotriptan binds to 5HT1B receptors, which are present in the coronary arteries. The administration may result in coronary artery narrowing or spasms, leading to potential coronary artery vasospasm or myocardial infarction.[18] Some rare side effects of almotriptan include pulmonary vasoconstriction, serotonin syndrome, and inhibition of trigeminal nerves.[19][20]

Contraindications

Box Warnings

Almotriptan is contraindicated in patients with renal dysfunction or insufficiency and with advanced age due to a physiological decrease in renal function and renal clearance with advanced age.[15] 

Minor almotriptan clearance 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.[15] Patients with reduced enzyme activity should be cautious in dosing the drug.

Warnings and Precautions

Contraindications to almotriptan include patients with underlying cardiovascular disease due to the presence of 5HT1B receptors in the coronary arteries. Almotriptan potentially binds to such receptors, further narrowing the arteries or spasms.[18] 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 used 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.[20] 

Monitoring

Patients prescribed almotriptan should be monitored 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 blood pressure monitoring should occur at each clinical visit due to the narrowing effect of the 5-HT1B receptors on the blood vessels to assess the drug's effectiveness.[20] 

Toxicity

There are no associated toxicities with almotriptan due to the limited data, although studies demonstrate increased preterm birth rates in pregnant women who were prescribed triptans for migraine relief.[21]

An analysis of several case reports of patients undergoing dual triptan-SSRI/SNRI, eg, 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, clinicians should remain cautious and vigilant of the symptoms.[22]

Enhancing Healthcare Team Outcomes

Managing the administration of almotriptan in patients with acute migraines requires an interprofessional team of healthcare professionals that includes a neurologist, primary care clinician, nephrologist if there is compromised renal function, psychiatrist, specialty-trained nursing staff, and pharmacist for appropriate dosing and safety precautions, working collaboratively to ensure optimal patient outcomes. 

Nurses must be ready to inform the prescriber of any potential adverse events from the medication and monitor whether almotriptan provides adequate relief for migraine pain. 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 of the patient's 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. This interprofessional team effort is necessary to optimize therapy with almotriptan so the patient can achieve the best outcomes.