What alternative treatments can be used for a migraine that is not responding to Ubrelvy (Ubrogepant)?

Immediate Rescue Options for Failed Ubrelvy

When Ubrelvy (ubrogepant) fails to provide relief, the patient should take an NSAID such as ibuprofen or naproxen sodium as the next step, or alternatively a triptan if the migraine is moderate to severe. 1, 2

First-Line Rescue Medications

NSAIDs (Preferred for Most Patients)

• Ibuprofen, naproxen sodium, or aspirin are appropriate rescue options when a CGRP antagonist like ubrogepant fails 1, 2
• These medications work through a different mechanism than ubrogepant, targeting prostaglandin-mediated inflammation rather than CGRP receptors 3
• NSAIDs have demonstrated efficacy in randomized controlled trials and are recommended as first-line therapy for mild to moderate attacks 1, 2

Triptans (For Moderate to Severe Attacks)

• Oral triptans (sumatriptan, rizatriptan, zolmitriptan, or naratriptan) are appropriate second-line options when ubrogepant fails, particularly if the migraine is moderate to severe 1, 3
• Triptans work through serotonin 1B/1D receptor agonism, a completely different pathway than CGRP antagonism 3
• Subcutaneous or intranasal sumatriptan should be considered if significant nausea or vomiting is present, as these routes bypass GI absorption 1

Combination Therapy Approach

• Acetaminophen + aspirin + caffeine combination can be effective when NSAIDs alone provide inadequate relief 1, 4
• This combination provides synergistic analgesia through multiple mechanisms 1

Antiemetic Options

• Metoclopramide 10 mg or prochlorperazine 10 mg can provide both antiemetic effects and direct analgesic benefit for migraine pain 1, 4
• These dopamine antagonists are particularly useful when nausea accompanies the headache 1

Alternative CGRP-Based Options

• Other CGRP antagonists (rimegepant or zavegepant) could theoretically be tried, though there is limited evidence for switching between gepants during the same attack 4
• Dihydroergotamine (DHE) intranasal represents an alternative acute treatment with good efficacy evidence 1, 4

Critical Medication-Overuse Warning

• Limit acute medication use to no more than twice weekly to prevent medication-overuse headache, which can transform episodic migraine into daily headaches 5, 1, 6
• If this patient is experiencing frequent migraines requiring repeated acute treatment, preventive therapy should be initiated rather than relying solely on rescue medications 5, 6

Medications to Avoid

• Opioids and butalbital-containing compounds should be avoided as they lead to dependency, medication-overuse headache, and loss of efficacy over time 1, 4, 3
• These agents are reserved only for situations where other medications are contraindicated and abuse risk has been addressed 1

Practical Algorithm

1. First attempt: NSAID (ibuprofen 400-800 mg or naproxen sodium 500-550 mg) 2, 3
2. If NSAID insufficient: Add acetaminophen + caffeine or switch to a triptan 1, 4
3. If nausea present: Add metoclopramide or prochlorperazine 1, 4
4. If all fail: Consider DHE intranasal or seek medical evaluation for parenteral therapy 1, 4