DrugindexOnline^{2nd edition}

Pronouncation: (al-moh-TRIP-tan MAL-ate)
Class: Serotonin 5-HT ₁ receptor agonist

Trade Names:
Axert
- Tablets 6.25 mg
- Tablets 12.5 mg

Mechanism of Action

Pharmacology

Selective agonist for vascular serotonin (5-HT) receptor subtype, causing vasoconstriction of cranial arteries.

Pharmacokinetics

Absorption

Well absorbed. T _max is 1 to 3 h. C _max is 49.5 to 64 mcg/L.

Distribution

Bioavailability is approximately 70%; approximately 35% is protein bound; Vd is approximately 180 to 200 L.

Metabolism

Metabolized to inactive metabolites by MAO-mediated oxidation (about 27%), CYP-450 (3A4 and 2D6)–mediated oxidation (about 12%), and flavin monooxygenase (minor).

Elimination

The t _½ is 3 to 4 h. About 75% is excreted by the kidneys (about 40% as unchanged drug). About 13% is excreted in feces.

Special Populations

Renal Function Impairment

Cl is decreased about 65% in those with Ccr 10 to 30 mL/min and decreased about 40% in those with Ccr 31 to 71 mL/min. C _max increased about 80%.

Hepatic Function Impairment

The max decrease expected in almotriptan Cl due to hepatic function impairment would be 60%.

Elderly

A longer t _½ (3.7 vs 3.2 h) and a 25% higher AUC has been observed in elderly patients.

Indications and Usage

Acute treatment of migraine with or without aura.

Contraindications

Ischemic heart disease (eg, angina pectoris, history of MI, documented silent ischemia); symptoms or findings consistent with ischemic heart disease; coronary artery vasospasm (including Prinzmetal variant angina); significant underlying CV disease; uncontrolled hypertension; within 24 h of treatment with another 5-HT ₁ agonist or ergotamine-containing or ergot-type medication; hemiplegic or basilar migraine; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO 6.25 to 12.5 mg. If headache returns, may repeat dose after 2 h (max, 2 doses per 24 h).

Hepatic or Renal Function Impairment
Adults

PO 6.25 mg initially (max, 12.5 mg per 24 h).

General Advice

• Administer prescribed dose at onset of migraine symptoms.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Ergot-containing drugs (eg, methysergide)

May cause prolonged vasospastic reactions; therefore, contraindicated within 24 h of almotriptan administration.

Other 5-HT _1B/1D agonists (eg, sumatriptan)

Contraindicated within 24 h of each other.

Potent CYP3A4 inhibitors (eg, erythromycin, itraconazole, ketoconazole, ritonavir)

Almotriptan plasma levels may be elevated, increasing the risk of adverse reactions.

Serotonin norepinephrine reuptake inhibitors (eg, venlafaxine), SSRIs (eg, fluoxetine)

Risk of life-threatening serotonin syndrome may be increased.

Verapamil

Almotriptan plasma concentrations may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Coronary artery vasospasm, intermediate coronary syndrome, MI (postmarketing).

CNS

Dizziness, headache, paresthesia, somnolence (at least 1%).

EENT

Dry mouth (at least 1%).

GI

Nausea (2%).

Precautions

Monitor CV evaluation Ensure that patients with potential for coronary artery disease (CAD), including postmenopausal women, men older than 40 yr of age, and patients with risk factors for CAD (eg, diabetes, family history, hypercholesterolemia, hypertension, obesity, smoking), undergo a CV evaluation before initiating therapy. Migraine evaluation Assess pain location, intensity, duration, and associated symptoms of migraine attack and response to treatment.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Safety and efficacy in patients older than 65 yr of age not established.

Renal Function

Cl is reduced; use with caution.

Hepatic Function

Cl is reduced; use with caution.

Cardiac events/vasoconstriction

Serious coronary events, though rare, can occur after administration of 5-HT ₁ agonists. It is strongly recommended that almotriptan not be given to patients in whom unrecognized CAD is predicted by presence of risk factors (eg, hypertension, obesity). For patients with CAD risk factors, administer first dose in health care provider's office or similarly staffed and equipped facility. Consider obtaining an ECG during interval following administration of first dose of medication to patient with potential for CAD. Coronary artery vasospasm, acute MI, life-threatening cardiac rhythm disturbances, and death have been reported.

Cerebrovascular events

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with 5-HT ₁ agonists.

Hypertensive crisis

Elevations in systemic BP, including hypertensive crisis, have been reported.

Serotonin syndrome

Potentially life-threatening serotonin syndrome may occur, particularly during coadministration of SSRIs or serotonin norepinephrine reuptake inhibitors.

Overdosage

Symptoms

Hypertension, serious CV symptoms.

Patient Information

• Advise patient to read the patient information leaflet before starting therapy and again with each refill.
• Explain that drug is to be used only during migraine and does not prevent or reduce the number of attacks. Emphasize that drug is used only to treat actual migraine attack.
• Advise patient that drug is to be taken as soon as symptoms of migraine appear. Second dose may be taken if symptoms return, but no sooner than 2 h following first dose. For a given attack, if there is no response to first tablet, do not take second tablet without first consulting health care provider. Do not take more than 2 tablets in any 24-h period.
• Advise patient that safety of treating more than 4 headaches in a 30-day period has not been established and to inform health care provider if headaches are occurring more frequently.
• Advise patient that if tightness, pain, pressure, or heaviness in chest or throat occurs when using almotriptan, notify health care provider before using drug again. Tell patient to notify health care provider immediately if chest pain is severe or does not go away.
• Advise patient to notify health care provider if feeling tingling, heat, heaviness, or pressure after treatment.
• Advise patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other activities requiring mental alertness.
• Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
• Instruct patient that if migraine prophylactic medications are prescribed, to continue to take daily as directed.
• Advise patient not currently taking a migraine prophylactic drug to discuss the use of such drugs with health care provider.