IM Migraine Cocktail Composition
The optimal intramuscular migraine cocktail consists of ketorolac 60 mg IM plus metoclopramide 10 mg IM, administered together for acute migraine treatment. 1
Primary Components
Ketorolac (NSAID Component)
- Dose: 60 mg IM for patients under 65 years of age 1
- Provides rapid onset of action with approximately 6 hours of analgesic duration 1
- Minimal risk of rebound headache compared to opioid-containing regimens 1
- Reduce dose for patients ≥65 years or with renal impairment 1
- Available as 30 mg/mL concentration, requiring 2 mL injection for full 60 mg dose 2
Metoclopramide (Dopamine Antagonist Component)
- Dose: 10 mg IM 1
- Provides direct analgesic effects through central dopamine receptor antagonism, independent of antiemetic properties 1, 3
- Delivers synergistic analgesia when combined with NSAIDs 1
- Addresses gastric stasis during migraine attacks, enhancing absorption of co-administered medications 1
- Available as 5 mg/mL concentration, requiring 2 mL injection 4
Mechanism of Synergy
The combination works through complementary pathways: ketorolac inhibits peripheral prostaglandin synthesis while metoclopramide provides central dopaminergic blockade with prokinetic effects 1. This dual mechanism addresses both the inflammatory component and the central sensitization of migraine pathophysiology 1.
Administration Protocol
- Both medications can be administered simultaneously via separate IM injection sites 1
- Onset of pain relief typically occurs within 30-60 minutes 5
- Maximum efficacy achieved by 2 hours post-injection 5
Critical Safety Considerations
Contraindications to Ketorolac
- Renal impairment (creatinine clearance <30 mL/min) 1
- Active GI bleeding or history of peptic ulcer disease 1
- Significant cardiovascular disease 1
- Aspirin/NSAID-induced asthma 1
Contraindications to Metoclopramide
- Pheochromocytoma 1
- Seizure disorder 1
- GI obstruction or bleeding 1
- Concurrent use with other dopamine antagonists 1
Frequency Limitation to Prevent Medication-Overuse Headache
Restrict use to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to chronic daily headaches 1. If patients require acute treatment more frequently, initiate preventive migraine therapy immediately rather than increasing acute medication frequency 1.
Alternative IM Options When First-Line Contraindicated
Prochlorperazine 10 mg IM
- Comparable efficacy to metoclopramide for migraine pain relief 1
- Can substitute for metoclopramide in the cocktail when combined with ketorolac 1
- Additional contraindications include CNS depression and concurrent adrenergic blocker use 1
Monotherapy Considerations
- If NSAIDs are contraindicated, metoclopramide 10 mg IM can be used as monotherapy with fair evidence for efficacy 3
- Ketorolac 60 mg IM alone demonstrated equivalence to chlorpromazine 25 mg IV in clinical trials, with mean pain scores decreasing from 4.07 to 0.73 over 2 hours 5
Common Pitfalls to Avoid
- Do not add opioids to this regimen, as they lead to dependency, rebound headaches, and eventual loss of efficacy 1, 6
- Do not add diphenhydramine routinely unless treating acute dystonic reactions, as sedation may complicate assessment and discharge 1
- Do not use this cocktail more than twice weekly, even if effective, as this creates medication-overuse headache 1
When to Escalate Beyond IM Cocktail
If the patient fails to respond to the IM cocktail after 2-3 migraine episodes, consider transitioning to IV dihydroergotamine (DHE) for refractory cases or initiating preventive therapy if attacks are frequent 1, 7.