What is a migraine cocktail, what is it made of and how is it administered?

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Last updated: October 13, 2025View editorial policy

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Migraine Cocktail: Composition and Administration

A migraine cocktail is a combination of medications typically administered intravenously in emergency or urgent care settings to treat severe migraine attacks, commonly consisting of an NSAID (usually ketorolac), an antiemetic (metoclopramide or prochlorperazine), and sometimes dihydroergotamine (DHE), administered via intravenous, intramuscular, or intranasal routes depending on the specific components.

Standard Components of a Migraine Cocktail

  • The primary components typically include an NSAID, most commonly ketorolac (30 mg IV), which provides rapid pain relief with approximately six hours of duration and minimal risk of rebound headache 1
  • An antiemetic such as metoclopramide (10 mg IV) or prochlorperazine (10 mg IV) is included not only to treat accompanying nausea but also to provide synergistic analgesia for migraine pain 1, 2
  • Dihydroergotamine (DHE), a semisynthetic ergot alkaloid and nonselective 5-HT1 receptor agonist, may be included for severe migraines, available in parenteral preparations (IV/IM) and as a nasal spray 2
  • The combination of IV metoclopramide (10 mg) plus IV ketorolac (30 mg) is recommended as first-line combination therapy for severe migraine attacks requiring intravenous treatment 1

Administration Routes and Methods

  • Intravenous (IV) administration is the most common route for migraine cocktails in emergency settings, providing rapid relief for severe attacks 1
  • Intramuscular (IM) administration may be used for DHE with a maximal initial dose of 0.5 to 1.0 mg, which can be repeated hourly to a maximal dosage of 3 mg IM per day 2
  • Intranasal administration is available for DHE as one 0.5-mg spray in each nostril, followed by one spray in each nostril 15 minutes later, with a maximum of four sprays (2 mg) per day 2
  • For patients with significant nausea and vomiting, non-oral routes of administration are preferred 1, 3

Alternative Components and Variations

  • Triptans may be included in some migraine cocktail variations, with subcutaneously injectable sumatriptan (Imitrex) reaching peak blood concentrations in approximately 15 minutes and showing effectiveness in 70-82% of patients 2
  • Subcutaneous sumatriptan (6 mg) provides the most rapid pain relief compared to other routes of administration, with pain reduced from moderate/severe to none in almost 6 in 10 people (59%) within two hours 4
  • Isometheptene combinations (such as Midrin) may be used in some cocktail formulations, though they show only borderline significance in relieving headache pain 2

Important Considerations and Cautions

  • Medication-overuse headache can result from frequent use of acute medications (more than twice weekly), leading to increasing headache frequency and potentially daily headaches 2, 1
  • DHE has contraindications including use with triptans, beta blockers, antihypertensives, pregnancy, and ergot alkaloid sensitivity 2
  • Triptans are contraindicated in patients with ischemic vascular conditions, vasospastic coronary disease, uncontrolled hypertension, or other significant cardiovascular disease 2, 5
  • Opioids should be avoided in migraine treatment as they can lead to dependency, rebound headaches, and eventual loss of efficacy 1, 3

Evidence-Based Administration Protocol

  • Treatment should begin as early as possible during the migraine attack to improve efficacy 1
  • For IV administration, metoclopramide (10 mg) is typically administered first to reduce nausea and improve gastric motility 3
  • This is followed by ketorolac (30 mg IV) for pain relief 1
  • If needed, DHE may be administered (0.5-1.0 mg IV/IM) and can be repeated hourly to a maximum of 3 mg IM or 2 mg IV per day 2
  • Patients should be monitored for adverse effects, particularly with DHE, which can cause ergot toxicity, coronary vasospasm, and cardiac events 2

By following this evidence-based approach to migraine cocktail administration, healthcare providers can effectively manage severe migraine attacks while minimizing adverse effects and reducing the risk of medication overuse headaches.

References

Guideline

Acute Headache Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Migraine Treatment Options Without Opiates or Diphenhydramine

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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