What are the side effects of triptans (sumatriptan, zolmitriptan, eletriptan) for migraine treatment?

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Triptan Side Effects

Triptans are generally well tolerated with common benign side effects including chest pressure/heaviness, paresthesias, dizziness, and nausea, but carry rare serious cardiovascular risks that contraindicate their use in patients with ischemic vascular disease, uncontrolled hypertension, or significant cardiovascular disease. 1, 2

Common Side Effects (Generally Mild and Self-Limited)

Sensory Disturbances

  • Chest pressure or heaviness (not indicative of cardiac ischemia in most cases) 1, 3, 2
  • Paresthesias (tingling or numbness), particularly in fingers and toes 1, 3, 2
  • Warmth or cold sensations throughout the body 1, 2

Neurological Effects

  • Dizziness and drowsiness 1, 2, 4
  • Weakness or fatigue 1, 2
  • Headache (paradoxically) 1

Gastrointestinal Effects

  • Nausea and vomiting 1, 2, 4
  • Dry mouth 4

Other Common Effects

  • Throat, neck, or jaw tightness/discomfort 1, 2, 4
  • Injection site reactions (for subcutaneous sumatriptan) 1
  • Malaise 1

Serious Adverse Events (Rare but Important)

Cardiovascular Events

  • Coronary vasospasm leading to angina, myocardial infarction, ventricular arrhythmias 1
  • Hypertension 1
  • Cerebrovascular events including stroke 1
  • Important context: Large epidemiological studies show no increased risk of stroke or MI in triptan users compared to non-users in real-world practice 5

Peripheral Vascular Events

  • Raynaud's syndrome (changes in color or sensation in fingers and toes) 2
  • Peripheral vascular ischemia with symptoms including leg cramping, pain, cold feeling, or color changes 2
  • Gastrointestinal and colonic ischemia presenting as severe stomach pain, bloody diarrhea, or weight loss 2

Serotonin Syndrome

  • Rare but potentially life-threatening when triptans are combined with SSRIs or SNRIs 2, 4, 6
  • Symptoms include mental status changes (hallucinations, agitation), fast heartbeat, blood pressure changes, high body temperature, muscle rigidity, and seizures 2, 4
  • Critical caveat: One large prospective study failed to document a single case, suggesting this risk may be overstated 6

Medication Overuse Headache

  • Chronic use leads to worsening headaches and increased headache frequency 2
  • Limit use to avoid this rebound phenomenon 1, 2

Drug-Specific Side Effect Profiles

Sumatriptan

  • Most data available given longest market presence (since 1991) 6
  • Injection form has highest rate of injection site reactions 1
  • Nausea, warmth, vertigo, malaise, chest pressure 1

Rizatriptan

  • Tachycardia, bradycardia, throat tightness 1
  • Requires dose adjustment with propranolol (drug interaction) 1

Zolmitriptan

  • Similar profile to other oral triptans 1
  • Pain, pressure or tightness in neck/throat/jaw, tingling, drowsiness 4

Naratriptan

  • Longest half-life may reduce recurrence headaches 1
  • Dizziness, drowsiness, nausea, fatigue, paresthesias 1

Eletriptan

  • Most complex pharmacokinetic profile due to CYP3A4 metabolism 7
  • Requires caution with CYP3A4 inhibitors 7
  • Favorable tolerability profile overall 7

Critical Safety Considerations

Absolute Contraindications

  • Ischemic vascular conditions (coronary, cerebral, or peripheral) 1, 8, 3
  • Vasospastic coronary disease 1
  • Uncontrolled hypertension 1
  • Hemiplegic or basilar migraine 1
  • Recent MAOI use (within 14 days) 1, 4
  • Concurrent ergotamine use (within 24 hours) 1

Important Drug Interactions

  • SSRIs and SNRIs: Risk of serotonin syndrome 1, 2, 4
  • Ergot derivatives: Additive vasospasm risk 1
  • MAOIs: Contraindicated 1, 4
  • Propranolol with rizatriptan: Requires dose reduction 1
  • CYP3A4 inhibitors with eletriptan: Avoid potent inhibitors 7

Clinical Management Pearls

  • If one triptan causes intolerable side effects, try a different triptan due to pharmacological differences between agents 3
  • Maximum daily dosing must be respected: Sumatriptan 200mg oral/12mg subcutaneous, rizatriptan 30mg, zolmitriptan 10mg 1, 2, 4
  • Overall safety profile is excellent with over 30 years of clinical experience and extensive postmarketing surveillance 6
  • Seizures have occurred in patients with no prior seizure history 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Triptans and Sensory Disturbances

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Safety profile of the triptans.

Expert opinion on drug safety, 2003

Guideline

Acute Migraine Treatment with Rizatriptan and Eletriptan

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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