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.1 12 13
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
Adults
Vascular Headaches
Migraine
Oral
5 or 10 mg as a single dose;1 individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 10-mg dose.1
Additional doses may be administered at intervals of ≥2 hours, up to a maximum dosage of 30 mg in any 24-hour period.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 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
Cautions for Maxalt
Contraindications
Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).1
Coronary artery vasospasm (e.g., Prinzmetal variant angina).1
Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).1
Hemiplegic or basilar migraine.1
Treatment within previous 24 hours with another 5-HT1 agonist or an ergot alkaloid.1 (See Specific Drugs under Interactions.)
Concurrent or recent (within 2 weeks) treatment with an MAO inhibitor.1 (See Specific Drugs under Interactions.)
Known hypersensitivity to rizatriptan 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
Exclude other potentially serious neurologic disorders before administering rizatriptan to patients not previously diagnosed with migraine or to those with atypical symptoms.14
Cardiac Effects
Possible myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbances, and death.1
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 rizatriptan should be evaluated for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; if administration 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 14
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).1 20 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
General Precautions
Ocular Effects
Possible accumulation of rizatriptan in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.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 1.05 or 2.1 mg of phenylalanine, respectively.1 Conventional tablets do not contain aspartame.1
Specific Populations
Pregnancy
Category C.1 Pregnancy Registry at 800-986-8999.18
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 <18 years of age; use not recommended.1
Geriatric Use
No substantial differences in efficacy, safety, or pharmacokinetic profile relative to younger adults; however, limited clinical experience in patients ≥65 years of age.1
Hepatic Impairment
Use with caution in patients with moderate hepatic impairment.1 (See Special Populations under Pharmacokinetics.)
Not studied in patients with severe hepatic impairment.17
Renal Impairment
Use with caution in patients undergoing dialysis.1 (See Special Populations under Pharmacokinetics.)
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 somnolence,1 4 dry mouth,1 4 nausea,1 4 paresthesia.1 4
Interactions for Maxalt
Metabolized by MAO-A.18
Does not inhibit CYP3A4/5, 1A2, 2C9, 2C19, or 2E1; inhibits CYP2D6 only at high concentrations.18
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 initiated1 20 |
β-Adrenergic blocking agents (metoprolol, nadolol, propranolol) | No pharmacokinetic interaction observed with metoprolol or nadolol1 22 Propranolol increased plasma rizatriptan concentrations in one study 1 | If used concomitantly with metoprolol or nadolol, no dosage adjustment required1 22 If used concomitantly with propranolol, maximum rizatriptan dosage of 5 mg per single dose and 3 doses per 24-hour period recommended1 |
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide) | 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 metabolite1 16 | Use within 2 weeks of MAO 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 (conventional tablets) or 1.6–2.5 hours (orally disintegrating tablets) after oral administration.1
AUC and peak plasma concentration are approximately 30 and 11% higher, respectively, in females than in males.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.18 Other minor metabolites, including an N-monodesmethyl derivative with similar activity to the parent compound, have been identified.18
Elimination Route
Excreted principally in urine (14% of dose as unchanged drug, 51% as indole acetic acid metabolite).18 19
Half-life
Approximately 2–3 hours.18
Special Populations
In patients with moderate hepatic impairment, plasma rizatriptan concentrations are approximately 30% higher than in healthy individuals.18
In hemodialysis patients, AUC is approximately 44% greater than in patients with normal renal function.18
Stability
Storage
Oral
Tablets
Tight containers at 15–30°C.18
Orally Disintegrating Tablets
15–30°C.18
ActionsActions
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
Importance of immediately informing clinician if tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw occurs 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 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
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 5 mg (of rizatriptan) | Maxalt | Merck |
10 mg (of rizatriptan) | Maxalt | Merck | ||
Tablets, orally disintegrating | 5 mg (of rizatriptan) | Maxalt-MLT (with aspartame) | Merck | |
10 mg (of rizatriptan) | Maxalt-MLT (with aspartame) | Merck |
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.
Maxalt 5MG Tablets (MERCK SHARP & DOHME): 12/$325.99 or 24/$634.99
Maxalt-MLT 10MG Dispersible Tablets (MERCK SHARP & DOHME): 6/$165.99 or 18/$475.98
Maxalt-MLT 5MG Dispersible Tablets (MERCK SHARP & DOHME): 3/$290.99 or 9/$851.96
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 September 2007. 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; 2006 Jun.
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]
14. Glaxo Wellcome Inc. Amerge (naratriptan hydrochloride) tablets prescribing information. Research Triangle Park, NC; 1999 Nov.
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.
18. Merck & Co., Inc. Maxalt (rizatriptan benzoate) tablets/Maxalt-MLT (rizatriptan benzoate) orally disintegrating tablets, prescribing information. Whitehouse Station, NJ; 2001 Oct.
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]
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