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Pronunciation

(rye za TRIP tan)

U.S. Brand Names

• Maxalt-MLT®
• Maxalt®

Index Terms

• MK462

Generic Available

No

Canadian Brand Names

• Maxalt RPD™
• Maxalt™

Pharmacologic Category

• Antimigraine Agent
• Serotonin 5-HT1B, 1D Receptor Agonist

Pharmacologic Category Synonyms

• Triptan

Use: Labeled Indications

Acute treatment of migraine with or without aura

Pregnancy Risk Factor

C

Pregnancy Considerations

There are no adequate and well-controlled studies using rizatriptan in pregnant women. Use only if potential benefit to the mother outweighs the potential risk to the fetus. A pregnancy registry has been established to monitor outcomes of women exposed to rizatriptan during pregnancy (800-986-8999). In some animal studies, administration was associated with decreased weight gain, developmental toxicity and increased mortality in the offspring. Teratogenic effects were not observed.

Lactation

Excretion in breast milk unknown/use caution

Contraindications

Hypersensitivity to rizatriptan or any component of the formulation; documented ischemic heart disease or Prinzmetal's angina; uncontrolled hypertension; basilar or hemiplegic migraine; during or within 2 weeks of MAO inhibitors; during or within 24 hours of treatment with another 5-HT₁ agonist, or an ergot-containing or ergot-type medication (eg, methysergide, dihydroergotamine)

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.

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.

• Renal impairment: Use with caution in dialysis patients.

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 rizatriptan'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.

Dosage form specific issues:

• Phenylalanine: Maxalt-MLT® tablets contain phenylalanine.

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.

Adverse Reactions

1% to 10%:

Cardiovascular: Systolic/diastolic blood pressure increases (5-10 mm Hg), chest pain (5%), palpitation

Central nervous system: Dizziness, drowsiness, fatigue (13% to 30%, dose related)

Dermatologic: Skin flushing

Endocrine & metabolic: Mild increase in growth hormone, hot flashes

Gastrointestinal: Abdominal pain, dry mouth (<5%), nausea

Respiratory: Dyspnea

<1%: Akinesia, angina, arrhythmia, arthralgia, blurred vision, bradykinesia, decreased mental activity, diaphoresis, diarrhea, dry eyes, eye pain, facial edema, bradycardia, chills, hangover, heat sensitivity muscle weakness, myalgia, nasopharyngeal irritation, neck pain/stiffness, neurological/psychiatric abnormalities, pharyngitis, polyuria, pruritus, syncope, tachycardia, tinnitus

Postmarketing and/or case reports: Angioedema, dysgeusia, myocardial ischemia, MI, stroke, toxic epidermal necrolysis, wheezing

Drug Interactions

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

Propranolol: May increase the serum concentration of Rizatriptan. Management: Rizatriptan dose should be reduced to 5mg in patients who are also being treated with propranolol. Risk D: Consider therapy modification

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

Ethanol/Nutrition/Herb Interactions

Food: Food delays absorption.

Storage

Store in blister pack until administration.

Mechanism of Action

Selective agonist for serotonin (5-HT_1B and 5-HT_1Dreceptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine

Pharmacodynamics/Kinetics

Onset of action: ~30 minutes

Duration: 14-16 hours

Protein binding: 14%

Metabolism: Via monoamine oxidase-A; first-pass effect

Bioavailability: 40% to 50%

Half-life elimination: 2-3 hours

Time to peak: 1-1.5 hours

Excretion: Urine (82%, 8% to 16% as unchanged drug); feces (12%)

Dosage

Note: In patients with risk factors for coronary artery disease, following adequate evaluation to establish the absence of coronary artery disease, the initial dose should be administered in a setting where response may be evaluated (physician's office or similarly staffed setting). ECG monitoring may be considered.

Oral: 5-10 mg, repeat after 2 hours if significant relief is not attained; maximum: 30 mg in a 24-hour period (use 5 mg dose in patients receiving propranolol with a maximum of 15 mg in 24 hours)

Note: For orally-disintegrating tablets (Maxalt-MLT®): Patient should be instructed to place tablet on tongue and allow to dissolve. Dissolved tablet will be swallowed with saliva.

Monitoring Parameters

Headache severity, signs/symptoms suggestive of angina; consider monitoring blood pressure, heart rate, and/or ECG with first dose in patients with likelihood of unrecognized coronary disease, such as patients with significant hypertension, hypercholesterolemia, obese patients, patients with diabetes, smokers with other risk factors or strong family history of coronary artery disease

Dietary Considerations

Orally-disintegrating tablet contains phenylalanine (1.05 mg per 5 mg tablet, 2.10 mg per 10 mg tablet).

Patient Education

This drug is to be used to reduce your migraine, not to prevent or reduce the number of attacks. Follow exact instructions for use. For orally-disintegrating tablets (Maxalt-MLT®), do not open blister pack before using. Open with dry hands, place on tongue, and allow to dissolve (dissolved tablet will be swallowed with saliva). Do not crush, break, or chew. Do not take within 24 hours of any other migraine medication without first consulting prescriber. If first dose brings relief, second dose may be taken anytime after 2 hours if migraine returns. Do not take more than two doses without consulting prescriber. May cause dizziness or drowsiness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth (frequent mouth care and sucking on lozenges may help); skin flushing or hot flashes (cool clothes or a cool environment may help); or mild abdominal discomfort or nausea or vomiting. Report immediately any chest pain, palpitations, or irregular heartbeat; severe dizziness, acute headache, stiff or painful neck or facial swelling; muscle weakness or pain; changes in mental acuity; blurred vision or eye pain; or excessive perspiration or urination. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

Geriatric Considerations

Since the elderly often have cardiovascular disease, careful evaluation of the use of 5-HT agonists is needed to avoid complications with the use of these agents. The pharmacokinetic disposition of these agents is similar to that seen in younger adults.

Anesthesia and Critical Care Concerns/Other Considerations

Clinical Pearls/Comments: Rizatriptan should not be used in patients with a history of vasospastic disease, Prinzmetal's angina, or any critical vascular disease.

Cardiovascular Considerations

Coronary vasospasm has been associated with 5-HT_1B/1D agonists. These agents are contraindicated in patients with documented ischemic of vasospastic coronary artery disease. Patients with risk factors for CAD may receive these agents, provided a cardiovascular evaluation yields satisfactory evidence that the patient is free of cardiovascular disease. In patients with risk factors for CAD, administration of the initial dose in a medically staffed/equipped facility (ie, physician's office) is recommended. In addition, ECG monitoring after the initial dose should be considered. Patients who acquire risk factors for CAD, or long-term users of agents from this class of medications, should undergo periodic cardiovascular evaluation.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Drowsiness and dizziness are common

Mental Health: Effects on Psychiatric Treatment

Contraindicated with other serotonin agonists (SSRIs) and MAO inhibitors

Nursing: Physical Assessment/Monitoring

For use only with clear diagnosis of migraine. Evaluate presence of or at risk for coronary disease. Initial dose should be administered in a setting where response may be evaluated and ECG monitoring may be considered. Assess potential for interactions with other pharmacological agents patient may be taking (eg, ergot containing drugs, SSRIs). Assess effectiveness (relief of migraine) and adverse response (eg, drowsiness, nausea/vomiting, chest pain, palpitations). Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:

Maxalt®: 5 mg, 10 mg

Tablet, orally disintegrating:

Maxalt-MLT®: 5 mg [contains phenylalanine 1.05 mg/tablet; peppermint flavor]; 10 mg [contains phenylalanine 2.1 mg/tablet; peppermint flavor]

Pricing: U.S. (www.drugstore.com)

Tablet, orally-disintegrating (Maxalt-MLT)

5 mg (3): $258.95

10 mg (6): $138.76

Tablets (Maxalt)

5 mg (6): $107.44

5 mg (12): $292.96

10 mg (12): $281.41

References

Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.

International Brand Names

• Maxalt (AR, AT, BE, BG, BR, CH, CN, CR, DE, DK, EE, ES, FI, GB, GR, GT, HN, HU, IT, MX, NL, NO, NZ, PA, PE, PL, SE, SV)
• Maxalt RPD (CN, PE, VE)
• Rizact (IN)
• Rizalt (IL)

Lexi-Comp.com

Last full review/revision August 2009

Content last modified August 2009