Which acute migraine medications can be safely taken with Ajovy (fremanezumab) for breakthrough attacks?

Acute Breakthrough Medications Safe to Use with Ajovy (Fremanezumab)

All standard acute migraine medications—including NSAIDs, triptans, gepants, ditans, and antiemetics—can be safely combined with Ajovy for breakthrough attacks, because fremanezumab is a preventive therapy that does not interact with acute treatments. 1, 2

First-Line Acute Treatment Options

For Mild-to-Moderate Breakthrough Attacks

• NSAIDs are the recommended first-line choice: ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg at attack onset. 3
• Combination therapy with acetaminophen 1000 mg + aspirin 500–1000 mg + caffeine 130 mg achieves pain reduction in 59.3% of patients at 2 hours. 4
• Add an antiemetic (metoclopramide 10 mg or prochlorperazine 25 mg) 20–30 minutes before the NSAID if nausea is present, as this provides synergistic analgesia beyond treating nausea alone. 4

For Moderate-to-Severe Breakthrough Attacks

• Triptans are first-line for moderate-to-severe attacks: sumatriptan 50–100 mg, rizatriptan 10 mg, eletriptan 40 mg, or zolmitriptan 2.5–5 mg. 3, 4
• The combination of triptan + NSAID is superior to either agent alone, with 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared to triptan monotherapy. 4
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes, making it ideal for rapid progression or severe nausea. 4
• Intranasal sumatriptan 5–20 mg is an effective alternative when oral routes are compromised by vomiting. 4

Second-Line Acute Options (When Triptans Fail or Are Contraindicated)

CGRP Antagonists (Gepants)

• Ubrogepant 50–100 mg or rimegepant are recommended as third-line options when triptans are inadequate or contraindicated (cardiovascular disease, uncontrolled hypertension). 4
• Gepants have no vasoconstriction, making them safe for patients with cardiovascular contraindications to triptans. 4
• Limit ubrogepant to ≤8 migraine attacks per 30-day period to prevent medication-overuse headache. 4

Ditans (Lasmiditan)

• Lasmiditan 50–200 mg is a 5-HT1F agonist without vasoconstrictor activity, safe for cardiovascular disease patients. 4
• Critical warning: patients must not drive or operate machinery for at least 8 hours after taking lasmiditan due to CNS effects (dizziness, somnolence). 4

Dihydroergotamine (DHE)

• Intranasal or IV dihydroergotamine has good evidence for efficacy as monotherapy for acute migraine. 3, 4
• Contraindications: concurrent triptan use within 24 hours, beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, sepsis. 4

Parenteral Options for Severe Attacks (Emergency/Urgent Care)

Intravenous Combination Therapy

• Metoclopramide 10 mg IV + ketorolac 30 mg IV is the recommended first-line IV combination for severe migraine requiring emergency treatment. 4
• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, independent of its antiemetic properties. 4
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk. 4

Alternative IV Options

• Prochlorperazine 10 mg IV is comparable to metoclopramide in efficacy with a more favorable side-effect profile (21% vs 50% adverse events). 4
• Dihydroergotamine 0.5–1.0 mg IV can be repeated every hour up to 2 mg per day when NSAIDs are contraindicated. 4

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit all acute migraine medications—regardless of class—to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 3, 4

• This 2-day-per-week limit applies to NSAIDs, triptans, gepants, ditans, combination analgesics, and all other acute agents. 4
• If you require acute treatment more than twice weekly despite Ajovy, immediately escalate preventive therapy rather than increasing acute medication frequency. 4
• Consider adding a second preventive agent (e.g., topiramate, beta-blocker) or switching to onabotulinumtoxinA if Ajovy alone is insufficient. 5

Medications to Absolutely Avoid

• Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) are absolutely contraindicated for migraine treatment because they provide questionable efficacy, carry high risk of dependence, cause rebound headaches, and worsen long-term outcomes. 3, 4
• Butalbital-containing compounds should be avoided due to high risk of medication-overuse headache and should be reserved only when all other evidence-based treatments are contraindicated. 4

Optimizing Ajovy Effectiveness

• Fremanezumab works in patients with medication overuse, previous treatment failures, and concomitant depression, improving both migraine and depression measures. 2
• Fremanezumab can be combined with onabotulinumtoxinA to improve resistance to migraine when monotherapy is insufficient. 2
• The typical reduction is 1–2 monthly migraine days over placebo in clinical trials, but real-world studies show greater magnitude of efficacy. 2
• Allow 3–6 months to assess full efficacy of Ajovy before declaring treatment failure. 5

When to Escalate Preventive Therapy

• If breakthrough attacks occur ≥2 days per week despite Ajovy, add a first-line oral preventive: propranolol 80–240 mg/day, topiramate 50–100 mg/day, or candesartan. 5
• If three oral preventives have failed in addition to Ajovy, escalate to onabotulinumtoxinA 155–195 U every 12 weeks. 4, 5
• Fremanezumab as add-on treatment to other preventive medications has demonstrated safety and efficacy in clinical trials. 6