MEDICATION SAFETY ISSUES
Axert® may be confused with Antivert®
U.S. BRAND NAMES — Axert®
Serotonin 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 (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
DOSING: PEDIATRIC — Migraine: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Severe renal impairment (Clcr ≤ 30 mL/minute): 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:
Axert®: 6.25 mg, 12.5 mg
DOSAGE FORMS: CONCISE
Axert®: 6.25 mg, 12.5 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — 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)
ADVERSE REACTIONS SIGNIFICANT
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% (Limited to important or life-threatening): Anaphylactic shock, angina, angioedema, breast pain, colitis, coronary artery vasospasm, hemiplegia, hypertension, myocardial ischemia, MI, neuropathy, rash, seizure, syncope, tachycardia, ventricular fibrillation, ventricular tachycardia, vertigo 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)
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 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,” the first dose of almotriptan should be given in the healthcare provider’s office. 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.
Special populations: Pediatrics: Safety and efficacy have not been established in children <12 years of age. 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.
METABOLISM / TRANSPORT EFFECTS — Substrate (minor) of CYP2D6, 3A4
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25mg and maximum dose to 12.5mg/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
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
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 embryoletha
lity, 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)
6.25 mg (6): $130.08
12.5 mg (12): $238.94
CANADIAN BRAND NAMES — Axert®
INTERNATIONAL BRAND NAMES — Almogran (BE, CH, DE, DK, ES, FI, FR, GB, IE, IS, IT, JP, NL, NO, PT, SE)
MECHANISM OF ACTION — Selective agonist for serotonin (5-HT1B and 5-HT1D 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: Vd: ~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
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)
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.