Axert

Generic Name: Almotriptan Malate
Class: Selective Serotonin Agonists
VA Class: CN105
Chemical Name: Hydroxybutanedioate-1-[[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]sulfonyl]pyrrolidine
Molecular Formula: C₁₇H₂₅N₃O₂S•C₄H₆O₅
CAS Number: 181183-52-8

Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).^{1 2 3 5 12}

Uses for Axert

Vascular Headaches

Acute treatment of migraine attacks with or without aura.^{1 9}

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.¹

Safety and efficacy not established for management of cluster headaches.¹

Axert Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.^{1 5 10 16}

Dosage

Available as almotriptan malate; dosage is expressed in terms of almotriptan.¹

Adults

Vascular Headaches

Migraine

Oral

6.25 or 12.5 mg as a single dose;^{1 4 5} individualize dosage selection,¹ weighing the possible benefit (greater effectiveness)^{1 4 5} and risks (increased adverse effects)⁷ of the 12.5-mg dose.⁷ In clinical studies, doses >12.5 mg did not lead to substantially greater response.¹

If headache recurs, dose may be repeated after 2 hours.¹

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.¹

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 12.5 mg as a single dose; do not exceed 2 doses in any 24-hour period.¹

Safety of treating an average of >4 headaches per 30-day period has not been established.¹

Special Populations

Hepatic Impairment

Initial dose of 6.25 mg; maximum dosage of 12.5 mg over a 24-hour period.¹

Renal Impairment

Initial dose of 6.25 mg; maximum dosage of 12.5 mg over a 24-hour period.¹

Geriatric Patients

Cautious dosage selection recommended; generally start at low end of dosing range due to greater frequency of decreased hepatic, renal, or cardiac function and of concomitant illnesses or other drug therapy in geriatric population.¹

In geriatric patients with normal renal function for their age, dosage is the same as that recommended for younger adults.¹

Cautions for Axert

Contraindications

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  Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).¹

  
  


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  Coronary artery vasospasm (e.g., Prinzmetal variant angina).¹

  
  


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  Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).¹

  
  


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  Hemiplegic or basilar migraine.¹

  
  


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  Treatment within previous 24 hours with another 5-HT₁ receptor agonist or an ergot alkaloid.¹ (See Specific Drugs under Interactions.)

  
  


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  Known hypersensitivity to almotriptan or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Use only in patients in whom a clear diagnosis of migraine has been established.¹

Cardiac Effects

Possible myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbances, and death.^{1 5}

Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.¹

Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician’s office, possibly followed by ECG) unless patient previously received the drug.¹

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.¹

Patients with symptoms suggestive of angina after receiving almotriptan should be evaluated for the presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; if administration is resumed and such signs or symptoms recur, ECG evaluation recommended.¹

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal.¹

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.¹

Other Cardiovascular or Vasospastic Effects

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported with use of 5-HT₁ receptor agonists.¹ Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic colitis, Raynaud’s phenomenon) occur following administration.¹

Substantial increases in BP, including hypertensive crises, reported rarely with 5-HT₁ receptor agonists in patients with or without history of hypertension.¹

Increases in mean pulmonary artery pressure observed following administration of a 5-HT₁ receptor agonist to patients with suspected CAD who were undergoing cardiac catheterization.¹

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT₁ receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs).^{11 a} Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).^{11 a}

General Precautions

Ocular Effects

Possible accumulation of almotriptan in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; not known whether distributed into milk in humans.¹ Caution advised if almotriptan is used.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.^{1 7}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.¹ (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution; dosage adjustment recommended.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution; dosage adjustment recommended.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea, somnolence, headache, paresthesia, dry mouth.¹

Interactions for Axert

Metabolized principally by MAO-A, CYP3A4, and CYP2D6.^{1 b}

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (decreased almotriptan metabolism) with concomitant use of CYP3A4 inhibitors.¹

Specific Drugs

Drug	Interaction	Comments
Alcohol	Pharmacokinetic or pharmacologic interaction unlikely15
Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)	Potentially life-threatening serotonin syndrome1 5 11 a Potential increase in plasma almotriptan concentrations with concurrent fluoxetine administration1 14	Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated1 11 a No dosage adjustment required if fluoxetine is used concomitantly1 14
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide)	Additive vasospastic effects1	Use within 24 hours contraindicated1 5
5-HT1 receptor agonists	Additive vasospastic effects1	Use within 24 hours contraindicated1 5
Itraconazole	Potential decrease in almotriptan metabolism1
Ketoconazole	Potential decrease in almotriptan metabolism1
MAO inhibitors	Potential decrease in almotriptan metabolism1	No dosage adjustment required1
Propranolol	Pharmacokinetic interaction unlikely1 5
Ritonavir	Potential decrease in almotriptan metabolism1
Verapamil	Potential increase in plasma almotriptan concentrations1 5	No dosage adjustment required1 5

Axert Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract.^{1 b} Absolute bioavailability is approximately 70%.^{1 b c}

Peak plasma concentrations attained within 1–3 hours after oral administration.^{1 b c}

Food

Food does not affect pharmacokinetics.^{1 10}

Distribution

Extent

Appears to be widely distributed throughout the body.^c

Distributed into milk in rats; not known whether distributed into milk in humans.¹

Plasma Protein Binding

Approximately 35%.¹

Elimination

Metabolism

Metabolized to inactive metabolites principally via MAO-mediated oxidative deamination, CYP3A4, and CYP2D6, with minor contribution of flavin monooxygenase.^{1 b}

Elimination Route

Excreted in urine (75%) and feces (13%), with 40% of dose recovered in urine as unchanged drug.¹

Half-life

3–4 hours.^{1 b c}

Special Populations

Pharmacokinetics not evaluated in patients with hepatic impairment.¹ Based on mechanism of almotriptan clearance, maximum decrease in clearance of 60% would be expected.¹

In patients with moderate or severe renal impairment, clearance is reduced by approximately 40 or 65%, respectively; peak plasma concentrations increased by approximately 80% in these patients.¹

In healthy geriatric patients, clearance is decreased, resulting in increases in half-life and AUC compared with younger adults; not considered clinically important.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

ActionsActions

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  Binds with high affinity to 5-HT_1D, 5-HT_1B, and 5-HT_1F receptors.¹

  
  


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  Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan).^{2 3 12}

  
  


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  Precise mechanism of action not established;⁷ may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.^{1 3 5 12}

  
  

Advice to Patients

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  Importance of immediately informing clinician if tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw occurs and of not taking almotriptan again until evaluated by clinician.¹

  
  


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  Importance of taking almotriptan exactly as prescribed.¹

  
  


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  Importance of providing patient a copy of manufacturer’s patient information.¹

  
  


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  Risk of somnolence; importance of exercising caution when driving or operating machinery.¹

  
  


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  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).¹

  
  


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  Importance of informing patients of risk of serotonin syndrome with concurrent use of almotriptan and an SSRI or SNRI.¹¹ Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.¹¹

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


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  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Almotriptan Malate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	6.25 mg (of almotriptan)	Axert	Ortho-McNeil
		12.5 mg (of almotriptan)	Axert	Ortho-McNeil

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Axert 12.5MG Tablets (ORTHO-MCNEIL PHARMACEUTICAL): 12/$308.98 or 36/$904.98

Axert 6.25MG Tablets (ORTHO-MCNEIL PHARMACEUTICAL): 6/$166.98 or 18/$475.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Ortho-McNeil Pharmaceutical, Inc. Axert (almotriptan malate) tablets prescribing information. Chicago, IL; 2005 Jun.

2. Deleu D, Hanssens Y. Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000; 40:687-700. [IDIS 449430] [PubMed 10883409]

3. Palacios JM, Rabasseda X, Castaner J et al. Almotriptan. Drugs Future. 1999; 24:367-74.

4. Pascual J, Falk RM, Piessens F et al. Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study. Cephalalgia. 2000; 20:588-96. [PubMed 11075844]

5. Pharmacia Corporation. Axert (almotriptan) tablets comprehensive review. Chicago, IL; 2001 Jan.

6. Spierings ELH, Gomez-Mancilla B, Grosz DE et al. Oral almotriptan vs oral sumatriptan in the abortive treatment of migraine. Arch Neurol. 2001; 58:944-50. [PubMed 11405809]

7. Pharmacia & Upjohn. Chicago, IL; Personal communication.

8. Pascaul J, Falk R, Docekal et al. Tolerability and efficacy of almotriptan in the long-term treatment of migraine. Eur Neurol. 2001; 45:206-13. [PubMed 11385257]

9. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. St. Paul, MN; 2001. From the American Academy of Neurology web site .

10. Jansat JM, Martinez-Tobed A, Garcia E et al. Effect of food intake on the bioavailability of almotriptan, an antimigraine compound, in healthy volunteers: an open, randomized, crossover, single-dose clinical trial. Int J Clin Pharmacol Ther. 2006; 44:185-90. [PubMed 16625988]

11. Food and Drug Administration. Public health advisory: combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephirne reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. Rockville, MD; 2006 Jul 19. From the FDA website: ( and , ).

12. Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000; 60:1259-87. [PubMed 11152011]

13. Fleishaker JC, Sisson TA, Carel BJ et al. Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers. Clin Pharmacol Ther. 2000; 67:498-503. [PubMed 10824628]

14. Fleishaker JC, Ryan KK, Carel BJ et al. Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers. J Clin Pharmacol. 2001; 41:217-23. [PubMed 11210405]

15. Cabarrocas X, Salva M, Pavesi M et al. Ethanol does not significantly affect the bioavailability of almotriptan: an open, randomized, crossover, single-dose, phase I clinical trial in healthy volunteers. Int J Clin Pharmacol Ther. 2006; 44:443-8. [PubMed 16995333]

16. Ortho-McNeil Pharmaceutical, Inc. Axert—Answers to FAQs. From the Ortho-McNeil website.

a. Ortho-McNeil Pharmaceutical, Inc. Axert (almotriptan malate) tablets prescribing information. Raritan, NJ; 2007 Jan.

b. Gras J, Llenas J, Jansat JM et al. Almotriptan, a new anti-migraine agent: a review. CNS Drug Rev. 2002; 8:217-34. [PubMed 12353056]

c. Jansat JM, Costa J, Salva P, Fernandez FJ, Martinez-Tobed A. Absolute bioavailability, pharmacokinetics, and urinary excretion of the novel antimigraine agent almotriptan in healthy male volunteers. J Clin Pharmacol. 2002; 42:1303-10. [PubMed 12463724]

More Axert resources

• Axert Side Effects (in more detail)
• Axert Use in Pregnancy & Breastfeeding
• Drug Images
• Axert Drug Interactions
• Axert Support Group
• 9 Reviews for Axert - Add your own review/rating

• Axert Prescribing Information (FDA)


• Axert Concise Consumer Information (Cerner Multum)


• Axert Advanced Consumer (Micromedex) - Includes Dosage Information


• Axert MedFacts Consumer Leaflet (Wolters Kluwer)

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