Rizatriptan - Drug Monograph

Introduction

Rizatriptan is a selective serotonin (5-HT1B/1D) receptor agonist belonging to the triptan class of medications. It is specifically designed for the acute treatment of migraine attacks with or without aura in adults. First approved by the FDA in 1998, rizatriptan represents an important therapeutic option for abortive migraine therapy.

Mechanism of Action

Rizatriptan exerts its therapeutic effects through selective agonism at serotonin 5-HT1B and 5-HT1D receptors. This action causes:

• Constriction of dilated cranial arteries
• Inhibition of neuropeptide release
• Reduction of trigeminal nerve transmission

The net effect is the reversal of the vasodilation and neurogenic inflammation that characterize migraine pathophysiology.

Indications

FDA-approved indications:

• Acute treatment of migraine with aura in adults
• Acute treatment of migraine without aura in adults

Not indicated for:

• Preventive migraine therapy
• Cluster headaches
• Hemiplegic or basilar migraine
• Management of other headache types

Dosage and Administration

• 5 mg or 10 mg tablet taken orally at migraine onset
• Maximum dose: 30 mg in 24 hours
• Minimum 2-hour interval between doses

• Hepatic impairment: Maximum 5 mg dose
• Renal impairment: No adjustment needed (CrCl >10 mL/min)
• Elderly: Use with caution (limited clinical experience)

• May be taken with or without food
• Orally disintegrating tablets: Place on tongue, allow to dissolve
• Conventional tablets: Swallow whole with water

Pharmacokinetics

• Rapid oral absorption
• Bioavailability: ~45%
• Tmax: 1-1.5 hours
• Food delays absorption by approximately 1 hour

• Protein binding: ~14%
• Volume of distribution: ~140 L

• Primarily metabolized via monoamine oxidase-A (MAO-A)
• Forms inactive indole acetic acid metabolite

• Half-life: 2-3 hours
• Renal excretion: ~82% (mostly as metabolite)
• Fecal excretion: ~12%

Contraindications

• History of coronary artery disease
• Uncontrolled hypertension
• History of stroke or TIA
• Peripheral vascular disease
• Ischemic bowel disease
• Hemiplegic or basilar migraine
• Concurrent MAO inhibitor use (or within 2 weeks)
• Hypersensitivity to rizatriptan or components
• Severe hepatic impairment

Warnings and Precautions

• May cause coronary artery vasospasm
• Risk of myocardial ischemia/infarction
• Blood pressure increases reported
• Perform cardiovascular evaluation in patients with multiple risk factors

• Potential for cerebrovascular events
• Screen for underlying cerebrovascular disease

• Risk when used with other serotonergic drugs
• Monitor for agitation, hallucinations, tachycardia

• Limit use to ≤10 days per month
• Monitor for development of chronic daily headache

• Orally disintegrating tablets contain phenylalanine

Drug Interactions

• MAO inhibitors: Increased rizatriptan levels (contraindicated)
• Propranolol: Increases rizatriptan AUC by 70%
• SSRIs/SNRIs: Increased serotonin syndrome risk
• Ergot derivatives: Prolonged vasospastic reactions
• Other triptans: Additive vasoconstrictive effects

• Use caution with other vasoconstrictors
• Monitor with CYP450 inhibitors

Adverse Effects

• Dizziness (9%)
• Somnolence (8%)
• Asthenia/fatigue (7%)
• Nausea (4%)
• Chest pain/tightness (4%)

• Myocardial infarction
• Stroke
• Coronary artery vasospasm
• Serotonin syndrome
• Arrhythmias
• Significant hypertension

Monitoring Parameters

• Cardiovascular assessment
• Blood pressure baseline
• Headache characteristics and frequency
• Medication overuse headache screening

• Headache response (2-hour pain freedom)
• Functional disability improvement
• Adverse effect profile
• Usage frequency (prevent medication overuse)
• Cardiovascular symptoms (chest pain, palpitations)

• Headache diary maintenance
• Development of chronic daily headache
• Changes in cardiovascular status

Patient Education

• Take at migraine onset, not for prevention
• Maximum 2 doses in 24 hours
• Wait at least 2 hours between doses

• Conventional tablets: Swallow with water
• Orally disintegrating tablets: Place on tongue to dissolve
• Do not break or crush tablets

• Report chest pain, shortness of breath, or severe dizziness immediately
• Avoid driving if drowsiness occurs
• Inform all healthcare providers of rizatriptan use
• Do not use with other migraine medications without consulting provider

• Maintain headache diary
• Identify and avoid migraine triggers
• Seek emergency care for unusual or severe symptoms

References

1. FDA Prescribing Information: Maxalt (rizatriptan benzoate) 2. Tfelt-Hansen P, et al. Guidelines for controlled trials of drugs in migraine: second edition. Cephalalgia. 2000;20(9):765-786. 3. Ferrari MD, et al. Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668-1675. 4. Tepper SJ, et al. Safety and efficacy of rizatriptan for acute migraine: a meta-analysis. Headache. 2013;53(4):643-659. 5. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18. 6. Goadsby PJ, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553-622.