What are the side effects of rizatriptan compared to naratriptan?

Side Effects Comparison: Rizatriptan vs Naratriptan

Rizatriptan causes significantly more adverse events than naratriptan (39% vs 29%), though both are generally well tolerated with mild and transient side effects. 1, 2

Common Side Effects Profile

Rizatriptan Side Effects

The FDA-approved labeling identifies the most common adverse reactions with rizatriptan (≥5% and greater than placebo) as: 3

• Asthenia/fatigue: 4-7% (dose-dependent)

• Somnolence: 4-8% (dose-dependent)

• Dizziness: 4-9% (dose-dependent)

• Pain/pressure sensations: 6-9% overall

  • Chest pain/tightness/pressure/heaviness: <2-3%
  • Neck/throat/jaw pain/tightness/pressure: <2-2%

• Gastrointestinal effects: 3

  • Dry mouth: 3%
  • Nausea: 4-6%
  • Diarrhea and vomiting (frequent, >1%)

• Atypical sensations: 4-5% (paresthesia 3-4%) 3

Naratriptan Side Effects

Naratriptan demonstrates a more favorable tolerability profile with: 4, 1

• Dizziness and asthenia/fatigue as the most common side effects
• Overall adverse event rate of 29% compared to rizatriptan's 39% 1, 2
• Comparable placebo-level tolerability with lower reported adverse event rates 5

Direct Comparative Evidence

Efficacy vs Tolerability Trade-off

The most recent head-to-head comparison demonstrates: 4, 1

• Rizatriptan provides superior efficacy (44.8% pain-free at 2 hours vs 20.7% for naratriptan) but at the cost of 34% higher adverse event rate 1, 2
• Naratriptan offers better tolerability with adverse event rates approaching placebo levels, making it appropriate for patients who have demonstrated poor tolerance to "triptan-type" adverse events 5

Cardiovascular Side Effects

Both medications share similar cardiovascular safety profiles: 1, 2

• Chest pain incidence is comparable: 2-4% for both rizatriptan and naratriptan
• Both can cause chest pressure, tightness, and heaviness as part of the triptan class effect 3

Serious Adverse Events (Class Effects)

Both medications carry identical FDA warnings for: 3

• Myocardial ischemia/infarction and stroke risk
• Vasospasm reactions (including coronary artery vasospasm)
• Serotonin syndrome when combined with SSRIs/SNRIs
• Medication overuse headache with frequent use (>2 days/week)
• Blood pressure elevation

Clinical Decision Algorithm

For patients prioritizing rapid efficacy and willing to accept higher adverse event rates: Use rizatriptan 10 mg, which provides faster onset (as early as 30 minutes) and higher 2-hour pain-free rates 4, 1

For patients with previous triptan intolerance or prioritizing tolerability: Use naratriptan 2.5 mg, which has placebo-comparable adverse event rates and lower recurrence rates for long-duration headaches 5, 6

For patients with frequent migraines requiring repeated dosing: Naratriptan's lower adverse event burden makes it more suitable for regular use, though both should be limited to ≤2 days/week to prevent medication overuse headache 7, 1

Critical Safety Considerations

• Rizatriptan requires dose reduction to 5 mg when used with propranolol due to MAO-A metabolite interactions 6
• Both medications are contraindicated within 24 hours of ergotamine-containing medications or other triptans 3
• Monitor for medication overuse headache if either agent is used more than twice weekly 3