Medication Guide App

Rizatriptan Benzoate

Pronunciation: RYE-za-TRIP-tan BEN-zoe-ate
Class: Serotonin 5-HT 1 receptor agonist

Trade Names

Maxalt
- Tablets, oral 5 mg
- Tablets, oral 10 mg

Maxalt-MLT
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg

Maxalt RPD (Canada)

Pharmacology

Binds to 5-HT 1B/1D receptors located on intracranial blood vessels and sensory nerves of the trigeminal systems.

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Pharmacokinetics

Absorption

Completely absorbed orally. Bioavailability is approximately 45%. T max is approximately 1 to 1.5 h. Food delays the T max by 1 h.

Distribution

Vd is 140 L in men and 110 L in women. Protein binding is 14%.

Metabolism

Extensive first pass metabolism via oxidative deamination by monoamine oxidase-A (MAO-A) to the indole acetic acid metabolite (inactive) and N-monodesmethyl-rizatriptan (active metabolite).

Elimination

Eliminated in urine (82%; 14% excreted as unchanged, 51% excreted as indole acetic acid metabolite) and feces (12%). Plasma half-life is 2 to 3 h.

Special Populations

Renal Function Impairment

In patients with CrCl 10 to 60 mL/min/1.73 m 2 , the AUC 0-∞ of rizatriptan was not significantly different. In hemodialysis patients (CrCl less than 2 mL/min/1.73 m 2 ), the AUC for rizatriptan was approximately 44% greater than that in patients with healthy renal function.

Hepatic Function Impairment

Plasma concentrations of rizatriptan were approximately 30% greater in patients with moderate hepatic insufficiency.

Elderly

Rizatriptan pharmacokinetics in healthy elderly nonmigraineur volunteers (65 to 77 y of age) were similar to those in younger nonmigraineur volunteers (18 to 45 y of age).

Children

Exposures were similar to those observed following a single dose to adults.

Gender

AUC is approximately 30% higher and C max is 11% higher in women than in men.

Race

Pharmacokinetic data revealed no significant differences between black and white subjects.

Indications and Usage

Treatment of acute migraine attacks with or without aura in adults and pediatric patients 6 to 17 y of age.

Contraindications

Ischemic heart disease (eg, angina pectoris, history of MI, documented silent ischemia) or other significant underlying CV disease; coronary artery vasospasm, including Prinzmetal variant angina; history of stroke or transient ischemic attack; peripheral vascular disease; ischemic bowel disease; uncontrolled hypertension; recent use (ie, within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide); hemiplegic or basilar migraine; coadministration or recent discontinuation (ie, within 2 weeks) of an MAO-A inhibitor; hypersensitivity to rizatriptan.

Dosage and Administration

Adults

PO 5 or 10 mg per migraine attack. A second dose may be repeated after a minimum of 2 h as needed (max, 30 mg per 24 hours).

Children (6 to 17 y of age)

PO For weight 40 kg or more, 10 mg per migraine attack; for weight 39 kg or less, 5 mg per migraine attack.

Concomitant therapy with propranolol
Adults

PO Only the 5 mg dose of rizatriptan is recommended, up to a maximum of 3 doses per 24 h (15 mg).

Children (6 to 17 y of age)

PO For weight 40 kg or more, only a single 5 mg dose of rizatriptan is recommended (max, 5 mg per 24 h). Do not coadminister rizatriptan and propranolol to patients who weigh less than 40 kg.

General Advice

  • The safety of treating, on average, more than 4 headaches in a 30-day period has not been established.
  • If a patient has no response to the first dose of rizatriptan, the diagnosis of migraine should be reconsidered before administration of a second dose.
  • Administration of the disintegrating tablets with liquid is not necessary.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

5-HT 1 agonists (eg, sumatriptan)

Increased risk of vasospastic reactions; therefore, coadministration of two 5-HT 1 agonists within 24 h of each other is contraindicated.

Ergot-containing drugs (eg, ergotamine)

Additive and prolonged vasospasm. Coadministration within 24 h is contraindicated.

MAOIs (eg, phenelzine)

Use of rizatriptan with MAOIs or within 14 days following discontinuation of an MAOI is contraindicated.

Propranolol

Increased rizatriptan plasma concentrations. The dose of rizatriptan should be adjusted.

Selective serotonin reuptake inhibitors (SSRIs) (eg, citalopram, fluoxetine, fluvoxamine, sertraline), serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, venlafaxine), tricyclic antidepressants (TCAs) (eg, amitriptyline)

Serotonin syndrome has been reported during coadministration of SSRIs, SNRIs, or TCAs and selective 5-HT 1 agonists. The onset of serotonin syndrome can occur within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Rizatriptan treatment should be discontinued if serotonin syndrome is suspected.

Sibutramine

Serotonin syndrome, including CNS irritability, motor weakness, shivering, myoclonus, and altered consciousness, may occur. Coadministration is not recommended.

Adverse Reactions

Cardiovascular

Palpitation (at least 1%); coronary artery vasospasm; hypertension; MI; stroke; transient myocardial ischemia; ventricular tachycardia; ventricular fibrillation.

CNS

Dizziness (9%); somnolence (8%); asthenia/fatigue (7%); paresthesia (4%); headache (2%); euphoria, hypoesthesia, tremor (at least 1%); seizure (postmarketing).

GI

Nausea (6%); dry mouth (3%); abdominal discomfort, diarrhea, vomiting (at least 1%); dysgeusia (postmarketing).

Hypersensitivity

Allergic conditions, including anaphylaxis/anaphylactoid reaction, angioedema, wheezing, and TEN (postmarketing).

Miscellaneous

Pain and other pressure sensations (9%); atypical sensations (5%); localized pain, pain, tightness, pressure, and/or heaviness of chest (3%); regional tightness, pressure, or heaviness, tightness, pain, or pressure of neck, throat, or jaw (2%); dyspnea, flushing, warm sensations (at least 1%).

Precautions

Monitor

Periodic CV evaluation should be considered in intermittent long-term users who have CV risk factors.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy in pediatric patients younger than 6 y have not been established.

Elderly

Use with caution.

Hypersensitivity

Angioedema and anaphylaxis have been seen in postmarketing experience.

Hazardous Tasks

Treatment may cause somnolence; dizziness has been reported.

Arrhythmias

Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following administration of 5-HT 1 agonists.

Coronary artery disease

May cause coronary artery vasospasm (Prinzmetal angina). Do not administer to patients with ischemic or vasospastic coronary artery disease or those with Prinzmetal variant angina. Rare reports of serious cardiac reactions, including acute MI, occurring within a few hours following administration, have occurred.

Cerebrovascular effects

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with 5-HT 1 agonists, some resulting in fatalities. Do not administer to patients with a history of stroke or transient ischemic attack.

Hypertension

Elevation in BP, including hypertensive crisis with acute impairment of organ systems, has been reported with administration of 5-HT 1 agonists.

Overuse

May lead to exacerbation of headache (medication overuse headache).

Phenylketonurics

The orally disintegrating tablets contain phenylalanine, a component of aspartame.

Serotonin syndrome

May occur, particularly during coadministration with SSRIs, SNRIs, TCAs, and MAOIs.

Vasospasm effects

May cause vasospastic reactions, such as peripheral vascular ischemia, GI vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud syndrome.

Overdosage

Symptoms

Abdominal discomfort, bradycardia including third-degree AV block, dizziness, dyspnea, fatigue, hypertension, incontinence, myocardial ischemia, somnolence, syncope, vomiting.

Patient Information

  • Inform patients that rizatriptan may cause serious CV adverse reactions, such as MI or stroke. Advise patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, and slurring of speech.
  • Inform patients about the risk of serotonin syndrome, particularly during combined use with SSRIs or SNRIs.
  • Inform patients that rizatriptan should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.
  • Advise patients to notify their health care provider if they are breast-feeding or planning to breast-feed.
  • Instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of rizatriptan.
  • Inform patients that use of acute migraine drugs for more than 10 days per month may lead to an exacerbation of headache. Encourage patients to record headache frequency and rizatriptan use (eg, by keeping a headache diary).
  • Instruct patients not to remove the blister from the outer aluminum pouch until ready to use the disintegrating tablet inside. The blister pack should then be peeled open with dry hands and the orally disintegrating tablet be placed on the tongue, where it will dissolve and be swallowed with saliva.
  • Inform phenylketonuric patients that rizatriptan disintegrating tablets contain phenylalanine (a component of aspartame). Each 5 mg disintegrating tablet contains phenylalanine 1.1 mg and each 10 mg disintegrating tablet contains phenylalanine 2.1 mg.

Copyright © 2009 Wolters Kluwer Health.

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