Almotriptan

Usage

• Almotriptan malate is prescribed for the acute treatment of migraine attacks in adults and adolescents (12-17 years old) with or without aura. It is not intended for migraine prevention or for other types of headaches like cluster headaches, hemiplegic migraine or basilar migraine. It is most effective when taken at the first sign of a migraine. Its use is restricted to situations where a clear diagnosis of migraine has been established.
• Pharmacological Classification: Selective serotonin (5-HT_1B/1D) receptor agonist, antimigraine agent.
• Mechanism of Action: Almotriptan selectively binds to 5-HT_1B/1D receptors located on intracranial blood vessels and sensory nerves associated with the trigeminal system. This binding leads to vasoconstriction of cranial blood vessels, reduces inflammation, and inhibits the release of pro-inflammatory neuropeptides, thus relieving migraine pain and associated symptoms like nausea, photophobia, and phonophobia.

Alternate Names

• International Nonproprietary Name (INN): Almotriptan.
• Brand Names: Axert, Dezamigren, Mylan-Almotriptan, Sandoz Almotriptan and various other generics.

How It Works

• Pharmacodynamics: Almotriptan exerts its therapeutic effect by acting as a selective agonist at 5-HT_1B and 5-HT_1D receptors. Stimulation of these receptors results in vasoconstriction of intracranial blood vessels, believed to be the primary mechanism of action in migraine relief. This action reduces vasodilation and neurogenic inflammation, which are key components of migraine pathophysiology. Additionally, almotriptan inhibits the release of calcitonin gene-related peptide (CGRP), a neuropeptide involved in pain transmission.

• Pharmacokinetics:

  • Absorption: Well-absorbed after oral administration, reaching peak plasma concentrations in 1 to 3 hours. Food does not significantly affect absorption.
  • Metabolism: Primarily metabolized by the liver, involving CYP3A4 enzymes.
  • Elimination: Excreted mainly in the urine, with a half-life of approximately 3 to 4 hours.

• Mode of Action: Almotriptan acts by binding to 5-HT_1B/1D receptors, causing:

  • Cranial Vasoconstriction: Reduces vasodilation of intracranial arteries.
  • Inhibition of Trigeminal Nerve Activation: Decreases the release of pro-inflammatory neuropeptides such as CGRP, substance P, and neurokinin A, thereby reducing pain transmission.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation:

  • Receptor Binding: Selective agonist at 5-HT_1B/1D receptors.
  • Enzyme Inhibition: Minimal inhibition of CYP isoenzymes.
  • Neurotransmitter Modulation: Inhibits the release of pro-inflammatory neuropeptides.

• Elimination Pathways: Primarily hepatic metabolism by CYP3A4, followed by renal excretion.

Dosage

Standard Dosage

Adults (18-65 years):

• Initial dose: 6.25 mg or 12.5 mg orally as a single dose. 12.5 mg is generally more effective.
• If migraine returns after initial relief, a second dose may be taken after at least 2 hours.
• Maximum daily dose: 25 mg (two 12.5 mg tablets or four 6.25 mg tablets).
• The benefit of a second dose if the first dose is ineffective has not been established.

Children (12-17 years):

• Initial dose: 6.25 mg or 12.5 mg orally as a single dose. Individualize dosage selection based on patient response.
• If headache returns, a second dose may be taken after 2 hours.
• Maximum daily dose: 25 mg.
• Safety and efficacy for treating more than four headaches in a 30-day period have not been established. Not for use in children under 12.

Special Cases:

• Elderly Patients (over 65 years): Start with a lower dose (6.25 mg) due to potential age-related decrease in renal, hepatic, or cardiac function.
• Patients with Renal Impairment:
  • Mild to moderate: No dosage adjustment is necessary.
  • Severe (Creatinine clearance < 30 mL/min): Initial dose: 6.25 mg; maximum daily dose: 12.5 mg.
• Patients with Hepatic Dysfunction: Initial dose: 6.25 mg; maximum daily dose: 12.5 mg.
• Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular risk factors.

Clinical Use Cases

Almotriptan is specifically indicated for the acute treatment of migraine attacks. It’s not intended for other clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations (e.g., status epilepticus, cardiac arrest).

Dosage Adjustments

• Concomitant Use with Potent CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole): Start with 6.25 mg; maximum daily dose: 12.5 mg. Avoid coadministration in patients with renal or hepatic impairment.

Side Effects

Common Side Effects:

• Dry mouth, nausea, vomiting.
• Numbness, tingling, or burning sensations (paresthesia).
• Dizziness, drowsiness, fatigue.
• Headache (not a migraine).
• Somnolence.

Rare but Serious Side Effects:

• Allergic reactions (e.g., hives, angioedema, difficulty breathing).
• Chest pain, tightness, or pressure (angina).
• Myocardial infarction, stroke.
• Serotonin syndrome.
• Peripheral vascular ischemia.
• Hypertension.
• Seizures (rare).
• Visual disturbances.
• Syncope.
• Vertigo.

Long-Term Effects:

Medication overuse headache (MOH) can occur with frequent triptan use.

Adverse Drug Reactions (ADR):

Severe allergic reactions, chest pain, myocardial infarction, stroke, serotonin syndrome, and peripheral vascular ischemia require urgent medical attention.

Contraindications

• Hypersensitivity to almotriptan.
• Ischemic heart disease (angina, history of myocardial infarction, silent ischemia).
• Coronary artery vasospasm (Prinzmetal’s angina).
• Uncontrolled hypertension.
• Other significant cardiovascular disease.
• Cerebrovascular syndromes (stroke, transient ischemic attack).
• Peripheral vascular disease (including ischemic bowel disease).
• Hemiplegic or basilar migraine.
• Use within 24 hours of another 5-HT₁ agonist (another triptan) or ergot-type medication (dihydroergotamine, ergotamine).

Drug Interactions

• CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole): Increased almotriptan levels, necessitating dosage reduction.
• Ergot-containing medications (e.g., ergotamine, dihydroergotamine): Additive vasoconstrictive effects; avoid concomitant use or use within 24 hours of each other.
• Other 5-HT₁ agonists (triptans): Additive effects; avoid concomitant use within 24 hours.
• Monoamine Oxidase Inhibitors (MAOIs): Increased risk of serotonin syndrome; avoid concomitant use or use within 2 weeks of discontinuing MAOIs.
• Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs): Increased risk of serotonin syndrome; monitor closely.
• St. John’s Wort may decrease almotriptan efficacy.

Pregnancy and Breastfeeding

• Pregnancy: Limited data available. Almotriptan may cause fetal harm. Use only if the potential benefit justifies the potential risk to the fetus. Advise patients to use effective contraception during treatment.

• Breastfeeding: Limited data available; caution advised. Almotriptan is present in breast milk. Consider avoiding breastfeeding for 24 hours after taking almotriptan or using an alternative medication. Discuss risks and benefits with the patient.

Drug Profile Summary

• Mechanism of Action: 5-HT_1B/1D receptor agonist, leading to cranial vasoconstriction and inhibition of trigeminal nerve activation.
• Side Effects: Common: Dry mouth, nausea, dizziness, paresthesia. Serious: Allergic reactions, chest pain, myocardial infarction, stroke.
• Contraindications: Cardiovascular disease, cerebrovascular disease, uncontrolled hypertension, concomitant use with ergot-containing medications or other triptans.
• Drug Interactions: CYP3A4 inhibitors, ergot alkaloids, MAOIs, SSRIs, SNRIs.
• Pregnancy & Breastfeeding: Limited data; potential fetal harm. Caution advised during breastfeeding.
• Dosage: Adults: 6.25 mg or 12.5 mg, max 25 mg/day. Children (12-17 years): 6.25 mg or 12.5 mg, max 25 mg/day. Special adjustments required for renal/hepatic impairment.
• Monitoring Parameters: Blood pressure, heart rate, and signs and symptoms of serotonin syndrome, myocardial ischemia or cerebrovascular events.

Popular Combinations

Almotriptan is typically used as monotherapy. Combining it with other migraine medications (e.g., NSAIDs, triptans) is generally not recommended due to the potential for additive side effects and increased risk of adverse events like medication overuse headache.

Precautions

• Assess cardiovascular risk factors before initiating therapy.
• Monitor blood pressure and cardiac function.
• Screen for pre-existing hepatic or renal impairment.
• Caution in patients with seizures, as almotriptan may lower seizure threshold.
• May cause drowsiness; avoid activities requiring alertness until effects are known.
• Encourage patients to maintain a headache diary to track triggers and treatment response.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Almotriptan?

A: Adults: 6.25 mg or 12.5 mg orally at the onset of a migraine attack. A second dose may be taken after 2 hours if needed, up to a maximum of 25 mg/day. Children (12-17 years): Same as adult dosing. Dosage adjustments are required for patients with hepatic or severe renal impairment (initial dose 6.25 mg, maximum daily dose 12.5 mg).

Q2: How does Almotriptan differ from other triptans?

A: Almotriptan is similar to other triptans in its mechanism of action and efficacy. It has a moderate half-life (3-4 hours). Individual patient response and tolerability to different triptans may vary, leading to a preference for one over another.

Q3: Can Almotriptan be used for migraine prevention?

A: No, Almotriptan is only indicated for acute treatment of migraine attacks, not for prevention. Preventive therapies should be considered for patients with frequent or severe migraines.

Q4: What are the most common side effects of Almotriptan?

A: The most common side effects are usually mild and transient, including dry mouth, nausea, dizziness, fatigue, somnolence and paresthesia.

Q5: What are the contraindications for using Almotriptan?

A: Almotriptan is contraindicated in patients with ischemic heart disease, cerebrovascular disease, uncontrolled hypertension, peripheral vascular disease, hemiplegic or basilar migraine, and within 24 hours of using another triptan or ergot alkaloid.

Q6: Can Almotriptan interact with other medications?

A: Yes. Clinically significant interactions can occur with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole), ergot alkaloids, MAOIs, other triptans, and some antidepressants (SSRIs, SNRIs). It is essential to review the patient’s medication list for potential interactions.

Q7: Can pregnant or breastfeeding women take Almotriptan?

A: Almotriptan should be used with caution during pregnancy and breastfeeding. There is limited data regarding safety. If the potential benefit justifies the potential risk to the fetus, it may be used during pregnancy. Breastfeeding women should avoid breastfeeding for 24 hours after taking almotriptan or consider using an alternative medication.

Q8: What should patients be advised about lifestyle modifications while taking Almotriptan?

A: Patients should be counseled on identifying and avoiding potential migraine triggers such as certain foods, stress, and changes in sleep patterns. Maintaining a headache diary can help identify these triggers. Patients experiencing drowsiness should avoid operating machinery or driving. Patients should also be cautioned against the overuse of almotriptan or other acute migraine medications, which can lead to medication overuse headache.

Q9: What is the first-line treatment for a patient experiencing their first migraine attack?

A: Almotriptan can be used as a first-line treatment but simple analgesics like paracetamol or ibuprofen could also be considered. If the first dose is ineffective, further investigation and a review of the diagnosis are needed.

Q10: How should almotriptan be stored?

A: Store at room temperature, away from moisture and heat. Keep out of reach of children.