Rescue Injection Medication for Acute Migraine
For adults presenting with acute migraine requiring injectable therapy, use subcutaneous sumatriptan 6 mg, intravenous prochlorperazine 10 mg, or intravenous metoclopramide 10 mg as first-line rescue injections. These three medications have the strongest evidence for efficacy and should be offered to eligible patients 1, 2.
First-Line Injectable Options
The 2025 American College of Physicians guideline and the updated 2025 American Headache Society emergency department guideline converge on clear first-line choices:
Subcutaneous Sumatriptan
- Dose: 6 mg subcutaneous injection
- Provides pain relief in 84% of patients within 60 minutes and 63% within 30 minutes 3
- Highly likely to be effective based on multiple class I studies 2
- Add an antiemetic if severe nausea or vomiting is present 1
- Available as pre-assembled auto-injector for ease of use 4
Intravenous Prochlorperazine
- Dose: 10 mg IV
- Must be offered (Level A recommendation) for ED migraine treatment 2
- Superior or equivalent to all other medication classes in multiple studies 5, 6
- Critical caveat: Higher risk of akathisia—consider prophylactic diphenhydramine 25-50 mg IV to prevent this distressing side effect 5
Intravenous Metoclopramide
- Dose: 10 mg IV
- Should be offered (Level B recommendation) 1, 2
- When combined with diphenhydramine, superior to triptans and NSAIDs 6
- Better tolerated than prochlorperazine with lower akathisia risk 5
Alternative Injectable Options
If first-line agents fail or are contraindicated:
Intravenous Ketorolac
- Dose: 30 mg IV
- Should be offered (Level B) 2
- NSAID option when triptans contraindicated (cardiovascular disease, uncontrolled hypertension)
- Generally well-tolerated even when given late in attack 6
Intravenous Dexketoprofen
- Should be offered based on recent evidence 2
- Another NSAID alternative with strong efficacy data
Greater Occipital Nerve Block (GONB)
- Must be offered (Level A) as non-pharmacologic injectable option 2
- Particularly useful when systemic medications contraindicated or failed
Critical Clinical Algorithm
Step 1: Assess for contraindications
- Cardiovascular disease, uncontrolled hypertension, hemiplegic migraine → avoid triptans, use metoclopramide or prochlorperazine
- Severe nausea/vomiting → add antiemetic regardless of choice
Step 2: Select based on setting and availability
- Outpatient/urgent care: Subcutaneous sumatriptan 6 mg (fastest, self-administrable)
- Emergency department: IV prochlorperazine 10 mg OR IV metoclopramide 10 mg (with diphenhydramine to prevent akathisia)
Step 3: Add dexamethasone for recurrence prevention
- Dose: 10-24 mg IV or IM
- Should be offered to prevent headache recurrence within 24-72 hours (Level B) 5, 2
- Reduces recurrence rate from >50% to significantly lower 6
What to Absolutely Avoid
Do not use opioids (morphine, hydromorphone, meperidine) or butalbital for acute migraine treatment 1. The 2025 guidelines explicitly state hydromorphone must not be offered (Level A) 2. These medications:
- Are likely ineffective based on class I evidence 2
- Increase risk of medication overuse headache
- Promote dependency and chronic migraine transformation
- Inferior to dopamine antagonists in head-to-head trials 6
Medication Overuse Warning
Counsel patients that using injectable triptans ≥10 days per month can cause medication overuse headache 1. For NSAIDs, the threshold is ≥15 days per month. If rescue therapy needed frequently, add preventive medications rather than increasing acute treatment frequency.
Special Populations
Pregnancy/lactation: Discuss risks of all pharmacologic treatments. Most injectable migraine medications lack safety data in pregnancy. Metoclopramide has the most reassuring pregnancy data among options discussed 1.
Cardiovascular risk factors: Use metoclopramide, prochlorperazine, or ketorolac instead of triptans, as newer gepants and lasmiditan are not yet available in injectable formulations 1, 7.