Medication Guide App

Generic Name: Rizatriptan Benzoate
Class: Selective Serotonin Agonists
VA Class: CN105
Chemical Name: N,N-Dimethyl-5-(1H-1,2,4-triazol-1-yl-methyl)-1H-indole-3-ethanamine monobenzoate
Molecular Formula: C15H19N5•C7H6O2
CAS Number: 145202-66-0

Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).1 2 3 21

Uses for Maxalt

Vascular Headaches

Acute treatment of migraine attacks with or without aura in adults1 12 13 and pediatric patients 6–17 years of age.1 24 Efficacy in reducing migraine-associated symptoms (nausea, photophobia, phonophobia) in pediatric patients not established.1 24

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

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

Maxalt Dosage and Administration

Administration

Oral Administration

Administer orally as conventional or orally disintegrating tablets without regard to meals.1

Just prior to administration of orally disintegrating tablet, remove blister from aluminum pouch; with dry hands, peel open blister package, place tablet on tongue to dissolve, and swallow with saliva.1

Administration of orally disintegrating tablet with liquid is not necessary.1

Dosage

Available as rizatriptan benzoate; dosage is expressed in terms of rizatriptan.1

Pediatric Patients

Vascular Headaches
Migraine
Oral

Pediatric patients 6–17 years of age: 5 mg as a single dose in patients weighing <40 kg, 10 mg as a single dose in those weighing ≥40 kg.1

Efficacy and safety of >1 dose within any 24-hour period not established.1

Adults

Vascular Headaches
Migraine
Oral

5 or 10 mg as a single dose;1 10-mg dose may provide greater effect than 5-mg dose, but may be associated with increased risk of adverse effects.1

If headache recurs, a second dose may be administered 2 hours after the first dose; maximum dosage of 30 mg in any 24-hour period.1

Prescribing Limits

Pediatric Patients

Vascular Headaches
Migraine
Oral

Efficacy and safety of >1 dose (5 mg in patients weighing <40 kg, 10 mg in those weighing ≥40 kg) in any 24-hour period not established.1

Adults

Vascular Headaches
Migraine
Oral

Maximum 30 mg 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

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosage range, because of greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.1

Cautions for Maxalt

Contraindications

  • Ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).1

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

  • Uncontrolled hypertension.1

  • Other serious underlying cardiovascular disease.1

  • History of stroke or TIA.1

  • Peripheral vascular disease or ischemic bowel disease.1

  • Hemiplegic or basilar migraine.1

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

  • Concurrent or recent (within 2 weeks) treatment with an MAO-A inhibitor.1 (See Specific Drugs under Interactions.)

  • Known hypersensitivity to rizatriptan or any ingredient in the formulation.1

Warnings/Precautions

Careful Diagnosis of Migraine

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

If first migraine attack treated with rizatriptan fails to respond to the drug, reconsider diagnosis before administering rizatriptan to treat subsequent attacks.1

Exclude other potentially serious neurologic disorders before administering rizatriptan to patients not previously diagnosed with migraine or to those with atypical symptoms.1

Cardiac Effects

Possible myocardial ischemia and/or infarction and coronary vasospasm, even in patients without a history of CAD.1 Contraindicated in patients with ischemic or vasospastic heart disease.1

Possible fatal or life-threatening cardiac rhythm disturbances (e.g., ventricular tachycardia or fibrillation).1 Discontinue if such disturbances occur.1

Tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw occur frequently but usually are noncardiac in origin.1 Manufacturer states that cardiovascular evaluation should be performed if a cardiac origin is suspected.1

Patients at Risk for CAD

Perform cardiovascular evaluation prior to initiating therapy in patients with multiple cardiovascular risk factors (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, family history of CAD) who have not previously received 5-HT1 receptor agonist therapy.1

If evaluation provides evidence of CAD or coronary vasospasm, do not administer the drug.1

If results of evaluation are satisfactory, consider administering the initial dose in a medically supervised setting followed immediately by an ECG.1

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

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage and stroke, sometimes fatal.1 (See Careful Diagnosis of Migraine under Cautions.) Discontinue therapy if a cerebrovascular event occurs.1

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

Other Vasospastic Effects

Possible noncoronary vasospastic reactions (e.g., peripheral vascular ischemia, GI ischemia and infarction with abdominal pain and bloody diarrhea, splenic infarction, Raynaud’s syndrome);1 transient or permanent blindness and partial vision loss reported in patients receiving 5-HT1 receptor agonists.1

If signs or symptoms suggestive of vasospasm occur following administration, evaluate patient to rule out vasospastic reaction before administering additional doses.1

Hypertensive Effects

Substantial increases in BP, including hypertensive crisis with acute impairment of organ systems, reported rarely with 5-HT1 receptor agonists in patients with or without history of hypertension.1

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported in patients receiving 5-HT1 receptor agonists, particularly in those receiving SSRIs or SNRIs concomitantly.1 20 (See Specific Drugs under Interactions.) Also may occur in patients receiving MAO inhibitors or tricyclic antidepressants concomitantly.1

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).1 20

If manifestations of serotonin syndrome occur, discontinue rizatriptan and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.1 33

Medication Overuse Headache

Overuse of drugs indicated for management of acute migraine attacks (e.g., use of 5-HT1 receptor agonists, ergotamine, opiates, or certain analgesic combinations on a regular basis for ≥10 days per month) may result in migraine-like daily headaches or a marked increase in frequency of migraine attacks.1 31 32

Detoxification, including withdrawal of overused drugs; treatment of withdrawal symptoms (e.g., transient worsening of headaches); and consideration of prophylactic migraine therapy may be necessary.1 31 32

Sensitivity Reactions

Hypersensitivity reactions (e.g., angioedema, anaphylaxis, wheezing, toxic epidermal necrolysis) reported.1

Phenylketonuria

Advise individuals who must restrict phenylalanine intake that each 5- or 10-mg Maxalt-MLT orally disintegrating tablet contains aspartame, which is metabolized in GI tract to provide 1.1 or 2.1 mg of phenylalanine, respectively.1 Conventional tablets do not contain aspartame.1

Generic preparations of rizatriptan also may contain aspartame; consult the manufacturer’s prescribing information.

Specific Populations

Pregnancy

Category C.1 Pregnancy registry at 800-986-8999.1

Lactation

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

Pediatric Use

Safety and efficacy not established in children <6 years of age.1 Adverse effects in pediatric patients expected to be similar to those in adults.1

Geriatric Use

No substantial differences in pharmacokinetic profile relative to younger adults; however, clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether response is different.1 Select dosage with caution.1

Hepatic Impairment

Not studied in patients with severe hepatic impairment.17

Common Adverse Effects

Pain/pressure sensations (i.e., chest pain [tightness/pressure/heaviness], pain/tightness/pressure in neck/throat/jaw, regional pain [tightness/pressure/heaviness], pain at location not specified),1 asthenia/fatigue,1 4 dizziness,1 4 headache,1 somnolence,1 4 dry mouth,1 4 nausea,1 4 paresthesia.1 4

Interactions for Maxalt

Metabolized by MAO-A.1

Does not inhibit CYP3A4/5, 1A2, 2C9, 2C19, or 2E1; inhibits CYP2D6 only at high concentrations.1

Specific Drugs

Drug

Interaction

Comments

Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)

Potentially life-threatening serotonin syndrome1 20

Study in healthy individuals showed no effect of paroxetine on plasma concentrations or safety profile of rizatriptan1 15

Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated20

β-Adrenergic blocking agents (metoprolol, nadolol, propranolol)

Metoprolol or nadolol: No pharmacokinetic interaction observed1 22

Propranolol: Increased plasma rizatriptan concentrations1

Metoprolol or nadolol: No dosage adjustment required1 22

Propranolol: Maximum rizatriptan dosage of 5 mg per single dose and 3 doses (15 mg total) per 24-hour period in adults; maximum 5 mg per single dose and 1 dose (5 mg total) per 24-hour period in pediatric patients weighing ≥40 kg; do not use concomitantly in pediatric patients weighing <40 kg1

Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide [no longer commercially available in the US])

Additive vasospastic effects1

Use within 24 hours contraindicated1

5-HT1 receptor agonists

Additive vasospastic effects1

Use within 24 hours contraindicated1

MAO inhibitors

Increased systemic exposure to rizatriptan and active N-monodesmethyl metabolite with MAO-A inhibitors1 16

Use within 2 weeks of MAO-A inhibitor contraindicated1

Oral contraceptives

Pharmacokinetic interaction unlikely1 23

Maxalt Pharmacokinetics

Absorption

Bioavailability

Completely absorbed from GI tract, 1 2 but absolute bioavailability (as conventional tablet) is 45%,1 indicating first-pass metabolism.1 2 Bioavailability is similar for orally disintegrating tablets.1

Peak plasma concentrations attained within 1–1.5 hours when administered as conventional tablets; peak concentrations are delayed by up to 0.7 hour when administered as orally disintegrating tablets.1

AUC and peak plasma concentration are approximately 30 and 11% higher, respectively, in females than in males.1

Exposure in pediatric patients 6–17 years of age receiving a single dose at recommended dosage levels is similar to that in adults receiving a single 10-mg dose.1

Food

Food does not substantially affect bioavailability but may delay time to peak concentration by 1 hour.1

Distribution

Extent

Crosses placenta and is distributed into milk in animals; no studies in pregnant or nursing women.1

Plasma Protein Binding

14%.1

Elimination

Metabolism

Metabolized principally via oxidative deamination by MAO-A to an inactive indole acetic acid metabolite.1 Other minor metabolites, including an N-monodesmethyl derivative with similar activity to the parent compound, have been identified.1

Elimination Route

Excreted principally in urine (14% of dose as unchanged drug, 51% as indole acetic acid metabolite).1 19

Half-life

Approximately 2–3 hours.1

Special Populations

In patients with moderate hepatic impairment, plasma rizatriptan concentrations are approximately 30% higher than in healthy individuals.1

In hemodialysis patients, AUC is approximately 44% greater than in patients with normal renal function.1 AUC in patients with CLcr of 10–60 mL/minute per 1.73 m2 is similar to that in healthy individuals.1

Pharmacokinetic profile in healthy geriatric individuals is similar to that in younger adults.1

Stability

Storage

Oral

Tablets

15–30°C.1

Orally Disintegrating Tablets

15–30°C.1

Actions

  • Binds with high affinity to 5-HT1B and 5-HT1D receptors.1 2 3 21

  • Structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, sumatriptan, zolmitriptan).1 2 21

  • Precise mechanism of action not established;1 2 3 may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.1 2 21

Advice to Patients

  • Risk of serious cardiovascular or cerebrovascular events (e.g., MI, stroke) or other vasospastic reactions.1 Importance of seeking medical care if symptoms of such reactions (e.g., shortness of breath, weakness, slurring of speech, sudden or severe abdominal pain, difficulty in seeing, or tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw) occur and of not taking rizatriptan again until evaluated by clinician.1

  • Importance of taking rizatriptan exactly as prescribed.1

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

  • Risk of dizziness, somnolence, and fatigue; importance of exercising caution when driving or operating machinery.1

  • For patients taking orally disintegrating tablets, importance of not removing the blister from the outer pouch until just before administering dose; importance of opening blister pack with dry hands and of placing tablet on tongue to dissolve and be swallowed with saliva.1

  • Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.1

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

  • Importance of informing patients of risk of serotonin syndrome, particularly with concurrent use of rizatriptan and an SSRI or SNRI.1 20 Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.1 20

  • Overuse of drugs indicated for the management of acute migraine attacks may exacerbate headaches; importance of recording headache frequency and drug use to monitor effectiveness of treatment.1 31

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

  • 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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Rizatriptan Benzoate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mg (of rizatriptan)*

Maxalt

Merck

Rizatriptan Benzoate Tablets

10 mg (of rizatriptan)*

Maxalt

Merck

Rizatriptan Benzoate Tablets

Tablets, orally disintegrating

5 mg (of rizatriptan)*

Maxalt-MLT

Merck

Rizatriptan Benzoate Orally Disintegrating Tablets

10 mg (of rizatriptan)*

Maxalt-MLT

Merck

Rizatriptan Benzoate Orally Disintegrating Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Maxalt 10MG Tablets (MERCK SHARP &amp; DOHME): 18/$531.96 or 54/$1,549.89

Maxalt 5MG Tablets (MERCK SHARP &amp; DOHME): 12/$353.69 or 24/$688.95

Maxalt-MLT 10MG Dispersible Tablets (MERCK SHARP &amp; DOHME): 3/$96.99 or 6/$184.97

Maxalt-MLT 5MG Dispersible Tablets (MERCK SHARP &amp; DOHME): 3/$315.72 or 9/$924.36

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 5, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Merck and Co., Inc. Maxalt (rizatriptan benzoate) tablets and Maxalt-MLT (rizatriptan benzoate) orally disintegrating tablets prescribing information. Whitehouse Station, NJ; 2013 Jan.

2. Goadsby PJ, Hargreaves RJ. Mechanisms of action of serotonin 5-HT1B/1D agonists: insights into migraine pathophysiology using rizatriptan. Neurology. 2000; 55(Suppl 2):S8-S14. [IDIS 455607] [PubMed 11089513]

3. Dooley M, Faulds D. Rizatriptan: a review of its efficacy in the management of migraine. Drugs. 1999; 58:699-723. [PubMed 10551439]

4. Kramer MS, Matzura-Wolfe D, Polis A et al. A placebo-controlled crossover study of rizatriptan in the treatment of multiple migraine attacks. Neurology. 1998; 51:773-81. [IDIS 414343] [PubMed 9748025]

5. Tfelt-Hansen P, Teall J, Rodriguez F et al. Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Headache. 1998; 38:748-55. [PubMed 11284463]

6. Teall J, Tuchman M, Cutler N et al. Rizatriptan (Maxalt) for the acute treatment of migraine and migraine recurrence. Headache. 1998; 38:281-7. [PubMed 9595867]

7. Lines C, Visser WH, Vandormael K et al. Rizatriptan 5 mg versus sumatriptan 50 mg in the acute treatment of migraine. Headache. 1997; 37:319-20.

8. Ahrens SP, Farmer MV, Williams DL et al. Efficacy and safety of rizatriptan wafer for the acute treatment of migraine. Cephalagia. 1999; 19:525-30.

9. Dahlof CGH, Rapoport AM, Sheftell FD et al. Rizatriptan in the treatment of migraine. Clin Ther. 1999; 21:1823-6. [IDIS 440855] [PubMed 10890255]

10. Block GA, Goldstein J, Polis A et al. Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Headache. 1998; 38:764-71. [PubMed 11284464]

11. Goldstein J, Ryan R, Jiang K et al. Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 and 50 mg in migraine. Headache. 1998; 38:737-47. [PubMed 11284462]

12. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. From American Academy of Neurology web site (http://www.aan.com).

13. Silberstein SD, for the US Headache Consortium. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2000; 55:754-63. [IDIS 453389] [PubMed 10993991]

15. Goldberg MR, Lowry RC, Musson DG et al. Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine. J Clin Pharmacol. 1999; 39:192-99. [IDIS 422446] [PubMed 11563413]

16. van Haarst AD, van Gerven JMA, Cohen AF et al. The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers. Br J Clin Pharmacol. 1999; 48:190-6. [IDIS 432034] [PubMed 10417495]

17. Merck, West Point, PA: Personal communication.

19. Vyas KP, Halpin RA, Geer LA et al. Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans. Drug Metab Dispos. 2000; 28:89-95. [IDIS 441742] [PubMed 10611145]

20. 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 ).

21. 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]

22. Goldberg MR, Sciberras D, De Smet M et al. Influence of beta-adrenoceptor antgaonists on the pharmacokinetics of rizatriptan, a 5HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol. Br J Clin Pharmacol. 2001; 52:69-76. [PubMed 11453892]

23. Shadle CR, Liu G, Goldberg MR. A double-blind, placebo-controlled evaluation of the effect of oral doses of rizatriptan 10 mg on oral contraceptive pharmacokinetics in healthy female volunteers. J Clin Pharmacol. 2000; 40:309-15. [PubMed 10709161]

24. Ho TW, Pearlman E, Lewis D et al. Efficacy and tolerability of rizatriptan in pediatric migraineurs: results from a randomized, double-blind, placebo-controlled trial using a novel adaptive enrichment design. Cephalalgia. 2012; 32:750-65. [PubMed 22711898]

31. Tepper SJ, Tepper DE. Breaking the cycle of medication overuse headache. Cleve Clin J Med. 2010; 77:236-42. [PubMed 20360117]

32. Negro A, Martelletti P. Chronic migraine plus medication overuse headache: two entities or not?. J Headache Pain. 2011; 12:593-601. [PubMed 21938457]

33. Bijl D. The serotonin syndrome. Neth J Med. 2004; 62:309-13. [PubMed 15635814]

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