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Rizatriptan

Pronunciation

(rye za TRIP tan)

Index Terms

  • MK462
  • Rizatriptan Benzoate

Dosage Forms

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

Tablet, Oral:

Maxalt: 5 mg, 10 mg

Generic: 5 mg, 10 mg

Tablet Dispersible, Oral:

Maxalt-MLT: 5 mg, 10 mg [contains aspartame; peppermint flavor]

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Maxalt
  • Maxalt-MLT

Pharmacologic Category

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

Pharmacology

Selective agonist for serotonin (5-HT1B and 5-HT1D receptors) in cranial arteries; causes vasoconstriction and reduces sterile inflammation associated with antidromic neuronal transmission correlating with relief of migraine

Absorption

Complete

Distribution

Vd: Females: 110 L; Males 140 L

Metabolism

Via monoamine oxidase-A; forms metabolites; significant first-pass metabolism

Excretion

Urine (82%, 14% as unchanged drug); feces (12%)

Onset of Action

Most patients have response to treatment within 2 hours

Time to Peak

Maxalt: 1 to 1.5 hours; Maxalt-MLT: 1.6 to 2.5 hours

Half-Life Elimination

2-3 hours

Protein Binding

14%

Special Populations: Renal Function Impairment

In patients with CrCl 10 to 60 mL/min/1.73 m2, the AUC0-∞ of rizatriptan was not significantly different. In hemodialysis patients (CrCl less than 2 mL/min/1.73 m2), the AUC for rizatriptan was approximately 44% greater than that in patients with healthy renal function.

Special Populations: Hepatic Function Impairment

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

Special Populations: 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).

Special Populations: Gender

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

Special Populations: Race

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

Use: Labeled Indications

Acute treatment of migraine with or without aura

Contraindications

Hypersensitivity to rizatriptan or any component of the formulation; documented ischemic heart disease or other significant cardiovascular disease; coronary artery vasospasm (including Prinzmetal's angina); history of stroke or transient ischemic attack; peripheral vascular disease; ischemic bowel disease; 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)

Dosing: Adult

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.

Migraine: Oral: 5-10 mg, repeat after 2 hours if significant relief is not attained; maximum: 30 mg/24 hours

Dose adjustment with concomitant propranolol therapy: 5 mg/dose (maximum: 15 mg/24 hours)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Migraine: Oral: Children 6-17 years: Note: Safety and efficacy of multiple rizatriptan doses in a 24-hour period have not been established for pediatric patients.

<40 kg: 5 mg as a single dose

≥40 kg: 10 mg as a single dose

Dose adjustment with concomitant propranolol therapy:

<40 kg: Use not recommended

≥40 kg: 5 mg as a single dose (maximum: 5 mg/24 hours)

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer's labeling; however, the AUC was 44% greater in patients on hemodialysis.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer's labeling; however, plasma concentrations are increased by 30% in patients with moderate hepatic dysfunction.

Administration

May be administered with or without food. 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.

Dietary Considerations

Some products may contain phenylalanine.

Storage

Store at room temperature of 15°C to 30°C (59°F to 86°F); orally disintegrating tablets should be stored in blister pack until administration.

Drug Interactions

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Droxidopa: Serotonin 5-HT1D Receptor Agonists may enhance the hypertensive effect of Droxidopa. Monitor therapy

Ergot Derivatives: Serotonin 5-HT1D Receptor Agonists may enhance the vasoconstricting effect of Ergot Derivatives. Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists. Exceptions: Nicergoline. 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. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

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

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

SUMAtriptan: Serotonin 5-HT1D Receptor Agonists may enhance the adverse/toxic effect of SUMAtriptan. Avoid combination

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Adverse Reactions

1% to 10%:

Cardiovascular: Chest pain (≤3%), flushing (>1%), palpitations (>1%), flushing

Central nervous system: Dizziness (4% to 9%), drowsiness (4% to 8%), fatigue (adults: 4% to 7%; children: >1%), paresthesia (3% to 4%), pain (3%), feeling of heaviness (≤2%), headache (≤2%), euphoria (>1%), hypoesthesia (>1%)

Gastrointestinal: Nausea (4% to 6%), xerostomia (3%), sore throat (≤2%), abdominal distress (children: >1%), diarrhea (>1%), vomiting (>1%)

Neuromuscular & skeletal: Weakness (4% to 7%), jaw pain (≤2%), jaw pressure (≤2%), jaw tightness (≤2%), neck pain (≤2%), neck pressure (≤2%), neck tightness (≤2%), tremor (>1%)

Respiratory: Pharyngeal edema (≤2%), pressure on pharynx (≤2%), dyspnea (>1%)

<1% (Limited to important or life-threatening): Anaphylaxis, anaphylactoid reaction, angina pectoris, angioedema, auditory impairment (children), blurred vision, bradycardia, confusion, edema, hallucination (children), hypertensive crisis, ischemic heart disease, memory impairment, myocardial infarction, pruritus, seizure, syncope, tachycardia, tinnitus, tongue edema, toxic epidermal necrolysis, vasospasm, vertigo, wheezing

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; if dosing is resumed and similar symptoms recur, monitor with ECG.

• Cerebrovascular events: Cerebral/subarachnoid hemorrhage and stroke have been reported with 5-HT1 agonist administration. Use is contraindicated in patients with a history of stroke or transient ischemic attack

• 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.

• Headaches: Acute migraine agents (eg, triptans, opioids, ergotamine, or a combination of the agents) used for 10 or more days per month may lead to worsening of headaches (medication overuse headache); withdrawal treatment may be necessary in the setting of overuse.

• Vasospasm-related events: Peripheral vascular ischemia and colonic ischemia, gastrointestinal ischemia/infarction, splenic infarction, and Raynaud’s syndrome have been reported with 5-HT1 agonist.

• Visual effects: Rarely, partial vision loss and blindness (transient and permanent) 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 (consider ECG monitoring). 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 (systemic exposure is increased).

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. If concomitant administration with SSRIs is warranted, monitor closely, especially at initiation and with dose increases.

Dosage form specific issues:

• Phenylalanine: Maxalt-MLT® tablets contain phenylalanine.

Other warnings/precautions:

• Appropriate use: Only indicated for treatment of acute migraine; not for the prevention of migraines or the treatment of cluster headache. If a patient does not respond to the first dose, the diagnosis of migraine should be reconsidered.

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Information related to rizatriptan use in pregnancy is limited (Källén, 2011; Nezvalová-Henriksen, 2010; Nezvalová-Henriksen, 2012).

A pregnancy registry has been established to monitor outcomes of women exposed to rizatriptan during pregnancy (800-986-8999). Preliminary data from the pregnancy registry (prospectively collected from 65 live births 1998-2004) does not show an increased risk of congenital malformations (Fiore, 2005). Until additional information is available, other agents are preferred for the initial treatment of migraine in pregnancy (Da Silva, 2012; MacGregor, 2012; Williams, 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, fatigue, feeling of heaviness, burning or numbness feeling, or loss of strength and energy. Have patient report immediately to prescriber signs of a heart attack (angina; pain in arms, back, neck, jaw, or stomach; shortness of breath; cold sweats; severe dizziness; passing out; or severe nausea or vomiting), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), severe headache, vision changes, blindness, constipation, diarrhea, severe nausea, severe vomiting, severe abdominal pain, bloody diarrhea, weight loss, leg cramps, leg pain, sensation of cold, burning or aching in feet or toes, shortness of breath, mood changes, skin discoloration, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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