Generic Name: rizatriptan

Brand Names: Maxalt, Maxalt-MLT

Uses

Vascular Headaches

Acute treatment of migraine attacks with or without aura.

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

Safety and efficacy not established for management of cluster headaches.

Dosage and Administration

Administration

Oral Administration

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

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.

Administration of orally disintegrating tablet with liquid is not necessary.

Dosage

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

Adults

Vascular Headaches

Migraine

Oral

5 or 10 mg as a single dose; individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 10-mg dose.

Additional doses may be administered at intervals of ≥2 hours, up to a maximum dosage of 30 mg in any 24-hour period.

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

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 30 mg in any 24-hour period.

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

Cautions

Contraindications

• Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).
• Coronary artery vasospasm (e.g., Prinzmetal variant angina).
• Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).
• Hemiplegic or basilar migraine.
• Treatment within previous 24 hours with another 5-HT₁ agonist or an ergot alkaloid. (See Specific Drugs under Interactions.)
• Concurrent or recent (within 2 weeks) treatment with an MAO inhibitor. (See Specific Drugs under Interactions.)
• Known hypersensitivity to rizatriptan or any ingredient in the formulation.

Warnings/Precautions

Warnings

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

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

Cardiac Effects

Possible myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbances, and death.

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.

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.

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

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.

Cerebrovascular Events

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

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

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. Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic colitis, Raynaud’s phenomenon) occur following administration.

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

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.

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). 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).

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.

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. Conventional tablets do not contain aspartame.

Specific Populations

Pregnancy

Category C. Pregnancy Registry at 800-986-8999.

Lactation

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

Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.

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.

Hepatic Impairment

Use with caution in patients with moderate hepatic impairment. (See Special Populations under Pharmacokinetics.)

Not studied in patients with severe hepatic impairment.

Renal Impairment

Use with caution in patients undergoing dialysis. (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), asthenia/fatigue, dizziness, somnolence, dry mouth, nausea, paresthesia.

Interactions

Metabolized by MAO-A.

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

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

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

Peak plasma concentrations attained within 1–1.5 hours (conventional tablets) or 1.6–2.5 hours (orally disintegrating tablets) after oral administration.

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

Food

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

Distribution

Extent

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

Plasma Protein Binding

14%.

Elimination

Metabolism

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

Elimination Route

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

Half-life

Approximately 2–3 hours.

Special Populations

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

In hemodialysis patients, AUC is approximately 44% greater than in patients with normal renal function.

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C.

Orally Disintegrating Tablets

15–30°C.

Actions

• Binds with high affinity to 5-HT_1B and 5-HT_1D receptors.
• Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, sumatriptan, zolmitriptan).
• Precise mechanism of action not established; may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.

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.
• Importance of taking rizatriptan exactly as prescribed.
• Importance of providing patient a copy of manufacturer’s patient information.
• Risk of dizziness, somnolence, and fatigue; importance of exercising caution when driving or operating machinery.
• 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.
• Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.
• 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).
• Importance of informing patients of risk of serotonin syndrome with concurrent use of rizatriptan and an SSRI or SNRI. Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions September 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.