This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources.

Pronunciation

(al moh TRIP tan)

Generic Available (U.S.)

No

Index Terms

• Almotriptan Malate

Brand Names: U.S.

• Axert®

Brand Names: Canada

• Axert®

Pharmacologic Category

• Antimigraine Agent
• Serotonin 5-HT1B, 1D Receptor Agonist

Pharmacologic Category Synonyms

• Triptan

Use: Labeled Indications

Acute treatment of migraine with or without aura in adults (with a history of migraine) and adolescents (with a history of migraine lasting ≥4 hours when left untreated)

Pregnancy Risk Factor

C

Pregnancy Considerations

There are no adequate and well-controlled studies in pregnant women. Use in pregnancy should be limited to situations where benefit outweighs risk to fetus. In some (but not all) animal studies, administration was associated with embryolethality, fetal malformations, and decreased pup weight.

Lactation

Excretion in breast milk unknown/use caution

Contraindications

Hypersensitivity to almotriptan or any component of the formulation; hemiplegic or basilar migraine; known or suspected ischemic heart disease (eg, angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); cerebrovascular syndromes (eg, stroke, transient ischemic attacks); peripheral vascular disease (eg, ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT₁ agonist; use within 24 hours of ergotamine derivatives and/or ergotamine-containing medications (eg, dihydroergotamine, ergotamine)

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac events: Coronary artery vasospasm, transient ischemia, myocardial infarction, ventricular tachycardia/fibrillation, cardiac arrest, and death have been reported with 5-HT₁ agonist administration. Patients who experience sensations of chest pain/pressure/tightness or symptoms suggestive of angina following dosing should be evaluated for coronary artery disease or Prinzmetal's angina before receiving additional doses; if dosing is resumed and similar symptoms recur, monitor with ECG.

• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT₁ agonist administration.

• Elevated blood pressure: Significant elevation in blood pressure, including hypertensive crisis, has been reported on rare occasions following 5-HT₁ agonist administration in patients with and without a history of hypertension.

• Ocular effects: Transient and permanent blindness and partial vision loss have been reported (rare) with 5-HT₁ agonist administration.

• Sulfonamide allergy: Almotriptan contains a sulfonyl group which is structurally different from a sulfonamide. Cross-reactivity in patients with sulfonamide allergy has not been evaluated; however, the manufacturer recommends that caution be exercised in this patient population.

• Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT₁ agonist administration.

Disease-related concerns:

• Coronary artery disease: Almotriptan should not be given to patients with documented ischemic or vasospastic CAD. Patients with risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) should undergo adequate cardiac evaluation prior to administration; if the cardiac evaluation is “satisfactory,” first dose should be given in the healthcare provider's office (consider ECG monitoring). All patients should undergo periodic evaluation of cardiovascular status during treatment.

• Hepatic impairment: Use with caution in patients with hepatic impairment. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended.

• Renal impairment: Use with caution in patients with moderate-to-severe renal failure. Drug clearance may be reduced leading to increased plasma concentrations; dosage reduction is recommended for severe renal impairment.

Concurrent drug therapy issues:

• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce almotriptan's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended. If concomitant administration with SSRIs is warranted, monitor closely, especially at initiation and with dose increases.

Special populations:

• Pediatrics: Efficacy has not been demonstrated in improvement of migraine-associated symptoms (eg, phonophobia, nausea, photophobia) in patients aged 12-17 years (Linder, 2008).

Other warnings/precautions:

• Appropriate use: Only indicated for treatment of acute migraine; it is not indicated for migraine prophylaxis, or for the treatment of cluster headaches, hemiplegic migraine, or basilar migraine. If a patient does not respond to the first dose, the diagnosis of acute migraine should be reconsidered.

Adverse Reactions

1% to 10%:

Central nervous system: Somnolence (≤5%), dizziness (≤4%), headache (≤2%)

Gastrointestinal: Nausea (1% to 3%), vomiting (≤2%), xerostomia (1%)

Neuromuscular & skeletal: Paresthesia (≤1%)

<1%, postmarketing, and/or case reports: Abdominal cramps, abdominal discomfort/pain, abnormal coordination, anaphylactic shock, angina, angioedema, anxiety, arthralgia, arthritis, back pain, blepharospasm, breast pain, bronchitis, chest pain, chills, colitis, confusion, conjunctivitis, coronary artery vasospasm, creatine phosphokinase increased, depressive symptoms, dermatitis, diaphoresis, diarrhea, diplopia, dream changes, dry eyes, dysmenorrhea, dyspepsia, dyspnea, ear pain, epistaxis, erythema, esophageal reflux, euphoria, eye irritation, eye pain, fatigue, fever, gastritis, gastroenteritis, GGTP increased, hemiplegia, hyperacusis, hypercholesterolemia, hyperglycemia, hyperhidrosis, hyper-reflexia, hypertension, hypertonia, hyperventilation, hypoesthesia, impaired concentration, insomnia, laryngismus, laryngitis, malaise, muscular weakness, myalgia, myocardial ischemia, MI, myopathy, neck pain, nervousness, neuropathy, nightmares, nystagmus, otitis media, pain in extremities, palpitation, parosmia, peripheral coldness, pharyngitis, photosensitivity reaction, pruritus, rash, restlessness, rhinitis, rigid neck, salivation increased, scotoma, seizure, shakiness, sinusitis, sneezing, stimulation, syncope, tachycardia, taste alterations, thirst, tinnitus, tremor, vasodilation, ventricular fibrillation, ventricular tachycardia, vertigo, weakness

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification

Ergot Derivatives: May enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Risk X: Avoid combination

MAO Inhibitors: May decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Mechanism of Action

Selective agonist for serotonin (5-HT_1B and 5-HT_1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine

Pharmacodynamics/Kinetics

Absorption: Well absorbed

Distribution: V_d: ~180-200 L

Protein binding: ~35%

Metabolism: Via MAO type A oxidative deamination (~27% of dose) and CYP3A4 and 2D6 (~12% of dose) to inactive metabolites

Bioavailability: ~70%

Half-life elimination: 3-4 hours

Time to peak, plasma: 1-3 hours

Excretion: Urine (~75%; ~40% of total dose as unchanged drug); feces (~13% of total dose as unchanged drug and metabolites)

Dosage

Oral: Children ≥12 years and Adults: Migraine: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours (maximum daily dose: 25 mg)

Note: The safety of treating more than 4 migraines/month has not been established.

Dosage adjustment with concomitant use of an enzyme inhibitor:

Patients receiving a potent CYP3A4 inhibitor: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg

Patients with renal impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use

Patients with hepatic impairment and concomitant use of a potent CYP3A4 inhibitor: Avoid use

Dosage adjustment in renal impairment: Severe renal impairment (Cl_cr ≤30 mL/minute): Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg

Dosage adjustment in hepatic impairment: Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg

Administration: Oral

Administer without regard to meals.

Dietary Considerations

May be taken without regard to meals.

Patient Education

This drug is to be used to reduce your migraine, not to prevent or reduce the number of attacks. Do not use more than two doses in 24 hours and do not take within 24 hours of any other migraine medication without consulting prescriber. May cause dizziness, fatigue, or drowsiness. Report immediately any chest pain or palpitations, feelings of tightness or pressure in jaw or throat, dizziness, or skin rash.

Geriatric Considerations

Use cautiously in elderly, particularly since many have cardiovascular disease, which would put them at risk for cardiovascular adverse effects. Safety and efficacy in elderly patients >65 years of age have not been established.

Cardiovascular Considerations

5-HT_1B/1D agonists have been associated with coronary vasospasm. These agents are contraindicated in patients with documented ischemic or vasospastic coronary artery disease. Patients with risk factors for CAD may receive these agents, provided a cardiovascular evaluation yields satisfactory evidence that the patient is free of cardiovascular disease. In patients with risk factors for CAD, administration of the initial dose in a medically staffed/equipped facility (ie, physician's office) is recommended. In addition, ECG monitoring after the initial dose should be considered. Patients who acquire risk factors for CAD, or long-term users of agents from this class of medications, should undergo periodic cardiovascular evaluation.

Dental Health: Effects on Dental Treatment

Key adverse effect(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation)

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Nursing: Physical Assessment/Monitoring

Clear diagnosis of migraines should be determined before beginning treatment. Cardiovascular status should be evaluated prior to initiating medication and periodically thereafter. Assess risk for coronary artery disease, liver or renal dysfunction, or sulfonamide allergy. Assess potential for interactions with ergot-containing drugs, SSRIs, and MAO inhibitors patient may be taking. Teach patient proper use (treatment of acute migraine; not prevention of migraine).

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral, as maleate:

Axert®: 6.25 mg, 12.5 mg

Pricing: U.S. (www.drugstore.com)

Tablets (Axert)

6.25 mg (6): $166.98

12.5 mg (12): $308.98

References

Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352(11):1112-20.

Chen LC and Ashcroft DM, “Meta-Analysis Examining the Efficacy and Safety of Almotriptan in the Acute Treatment of Migraine,” Headache, 2007, 47(8):1169-77.

Freitag F, Smith T, Mathew N, et al, “Effect of Early Intervention With Almotriptan vs. Placebo on Migraine-Associated Functional Disability: Results from the AEGIS Trial,” Headache, 2008, 48(3):341-54.

Goadsby PJ, Zanchin G, Geraud G, et al, “Early vs. Non-Early Intervention in Acute Migraine—‘Act when Mild (AwM)'. A Double-Blind, Placebo-Controlled Trial of Almotriptan,” Cephalalgia, 2008, 28(4):383-91.

Linder SL, Mathew NT, Cady RK, et al, “Efficacy and Tolerability of Almotriptan in Adolescents: A Randomized, Double-Blind, Placebo-Controlled Trial,” Headache, 2008, 48(9):1326-36.

Mathew NT, Finlayson G, Smith TR, et al, “Early Intervention With Almotriptan: Results of the AEGIS Trial (AXERT® Early Migraine Intervention Study),” Headache, 2007, 47(2):189-98.

Mazzoleni R, Kreisler A, Lucas C, et al, “Seizure After Use of Almotriptan,” Clin NeurolNeurosurg, 2008, 110(8):850-1.

McEnroe JD and Fleishaker JC, “Clinical Pharmacokinetics of Almotriptan, a Serotonin 5-HT1B/1DReceptor Agonist for the Treatment of Migraine,” Clin Pharmacokinet, 2005, 44(3):237-46.

International Brand Names

• Almogran (AT, BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, KP, NL, NO, PT, SE)
• Amignul (GR)

Lexi-Comp.com

Last full review/revision October 2011

Content last modified October 2011