Almotriptan

U.S. BRAND NAMES — Axert™
PHARMACOLOGIC CATEGORY Antimigraine AgentSerotonin 5-HT1B, 1D Receptor Agonist
DOSING: ADULTS — Migraine: Oral: Initial: 6.25-12.5 mg in a single dose; if the headache returns, repeat the dose after 2 hours; no more than 2 doses in 24-hour period
Note: If the first dose is ineffective, diagnosis needs to be re-evaluated. Safety of treating more than 4 migraines/month has not been established.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSING: HEPATIC IMPAIRMENT — Initial: 6.25 mg in a single dose; maximum daily dose: 12.5 mg
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as malate: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE Tablet: Axert™: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Acute treatment of migraine with or without aura
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Headache (>1%), dizziness (>1%), somnolence (>1%) Gastrointestinal: Nausea (1% to 2%), xerostomia (1%) Neuromuscular & skeletal: Paresthesia (1%)
<1% (Limited to important or life-threatening): Colitis, coronary artery vasospasm, hypertension, myocardial ischemia, MI, neuropathy, rash, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo
CONTRAINDICATIONS — Hypersensitivity to almotriptan or any component of the formulation; use as prophylactic therapy for migraine; hemiplegic or basilar migraine; cluster headache; known or suspected ischemic heart disease (angina pectoris, MI, documented silent ischemia, coronary artery vasospasm, Prinzmetal's variant angina); peripheral vascular syndromes (including ischemic bowel disease); uncontrolled hypertension; use within 24 hours of another 5-HT1 agonist; use within 24 hours of ergotamine derivative; concurrent administration or within 2 weeks of discontinuing an MAO inhibitor (specifically MAO type A inhibitors)
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. 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 also been reported on rare occasions in patients with and without a history of hypertension. Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia have been reported with 5-HT1 agonist. administration.
Disease-related concerns: Coronary artery disease: Should not be given to patients who have risk factors for CAD (eg, hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, menopause, male >40 years of age) without adequate cardiac evaluation. Patients with suspected CAD should have cardiovascular evaluation to rule out CAD before considering use; if cardiovascular evaluation "is satisfactory", first dose should be given in the healthcare provider's office. Periodic evaluation of cardiovascular status should be done in all patients. 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.
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.
Special populations: Pediatrics: Safety and efficacy have not been established in children <18 years of age.
Other warnings/precautions: Appropriate use: Only indicated for treatment of acute migraine; if a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered.
DRUG INTERACTIONS — Substrate (minor) of CYP2D6, 3A4
Ergot-containing drugs: Prolong vasospastic reactions; do not use almotriptan or ergot-containing drugs within 24 hours of each other.
Ketoconazole: Increases almotriptan serum concentration. Monitor for increased almotriptan response.
MAO inhibitors (moclobemide [MAO type A inhibitor]): Almotriptan clearance decreased by 27%; Cmax increased by 6%. Avoid concurrent administration of MAO inhibitors or within 2 weeks of discontinuing an MAO inhibitor, specifically MAO type A inhibitors.
Selegiline: Selegiline is a selective MAO type B inhibitor; while not specifically contraindicated, combination has not been studied.
Verapamil: Increased almotriptan serum concentration by 24%. Dose adjustment not necessary.
Serotonin agonists (eg, triptans): Concurrent use of almotriptan with these agents may increase the risk of serotonin syndrome; monitor.
Serotonergic reuptake inhibitors (eg, SSRIs/SNRIs): Concurrent use of almotriptan with these agents may increase the risk of serotonin syndrome; monitor.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — 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
DIETARY CONSIDERATIONS — May be taken without regard to meals
PRICING — (data from drugstore.com)Tablets (Axert) 6.25 mg (6): $120.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Hypertension or more serious cardiovascular symptoms may occur. Clinical and electrocardiographic monitoring is needed for at least 20 hours even if patient is asymptomatic. Treatment is symptom-directed and supportive.
CANADIAN BRAND NAMES — Axert™
INTERNATIONAL BRAND NAMES — Almogran (BE, DE, DK, FI, FR, GB, IE, IT, NL); Axert® (CA)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B, 5-HT1D, 5-HT1F receptors) in cranial arteries; causes vasoconstriction and reduce sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine
PHARMACODYNAMICS / KINETICS Absorption: Well absorbed
Distribution: Vd: 180-200 L
Protein binding: ~35%
Metabolism: MAO type A oxidative deamination (~27% of dose); via CYP3A4 and 2D6 (~12% of dose) to inactive metabolites
Bioavailability: 70%
Half-life elimination: 3-4 hours
Time to peak: 1-3 hours
Excretion: Urine (40% as unchanged drug); feces (13% unchanged and metabolized)
PATIENT INFORMATION — This drug is to be used to reduce your migraine not to prevent or reduce the number of attacks. Take exactly as directed. If headache returns or is not fully resolved, the dose may be repeated after 2 hours. Do not use more than two doses in 24 hours. Do not take within 24 hours of other migraine medication without consulting prescriber. You may experience dizziness, fatigue, or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known). Report immediately chest pain, palpitations, feeling of tightness or pressure in chest, jaw, or throat; acute headache or dizziness; muscle cramping, pain, or tremors; skin rash; hallucinations, anxiety, panic; or other adverse reactions.