What are the alternatives to Ubrelvy (ubrogepant) for managing migraine headaches?

Alternatives to Ubrelvy (Ubrogepant) for Acute Migraine Management

For acute migraine treatment, triptans (sumatriptan, rizatriptan, naratriptan, zolmitriptan) remain first-line options for moderate-to-severe attacks, while NSAIDs (ibuprofen, naproxen, aspirin-acetaminophen-caffeine combinations) are first-line for mild-to-moderate attacks, and newer gepants (rimegepant, zavegepant) serve as alternatives when triptans are contraindicated or ineffective. 1, 2

First-Line Alternatives by Attack Severity

For Mild-to-Moderate Migraine Attacks

• NSAIDs are the primary first-line option, including ibuprofen (400 mg), naproxen sodium (500-825 mg), aspirin, and diclofenac potassium 1, 2
• Combination therapy with aspirin-acetaminophen-caffeine provides synergistic analgesia and is particularly effective when single-agent NSAIDs provide inadequate relief 1, 2
• Begin treatment as early as possible during the attack while pain is still mild to maximize efficacy 2

For Moderate-to-Severe Migraine Attacks

• Triptans are the primary alternative, with oral options including sumatriptan, rizatriptan, naratriptan, and zolmitriptan 1, 2
• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours), making it ideal for severe attacks or when rapid onset is needed 2
• Intranasal sumatriptan (5-20 mg) is particularly useful when significant nausea or vomiting is present 2
• If one triptan fails, try a different triptan before abandoning the class entirely, as failure of one does not predict failure of others 2

Second-Line Alternatives

Other Gepants (Same Class as Ubrelvy)

• Rimegepant is an alternative oral CGRP receptor antagonist with similar mechanism to ubrogepant 2, 3
• Zavegepant is a newer gepant option when other treatments are contraindicated or ineffective 2

Antiemetic Monotherapy

• Intravenous metoclopramide (10 mg) provides direct analgesic effects through dopamine receptor antagonism, not just antiemetic effects 2
• Prochlorperazine (10 mg IV) effectively relieves headache pain and is comparable to metoclopramide in efficacy 2
• These agents work synergistically when combined with NSAIDs or triptans 2

Dihydroergotamine (DHE)

• Intranasal DHE has good evidence for efficacy and safety as monotherapy for acute migraine attacks 1, 2
• Particularly useful for patients with contraindications to triptans or when triptans have failed 2

Intravenous "Migraine Cocktail" for Severe Attacks

• Ketorolac 30 mg IV plus metoclopramide 10 mg IV is the recommended first-line IV combination for severe migraine requiring emergency/urgent care treatment 2
• Ketorolac provides rapid onset with approximately 6 hours duration and minimal rebound headache risk 2
• Prochlorperazine 10 mg IV can substitute for metoclopramide with comparable efficacy 2

Critical Medications to Avoid

• Opioids (including hydromorphone, oxycodone combinations) should be reserved only for cases where all other options cannot be used, as they lead to dependency, rebound headaches, and loss of efficacy 1, 2
• Butalbital-containing compounds carry similar risks of medication-overuse headache 2
• Oral ergot alkaloids have questionable efficacy and significant adverse effects 4

Algorithm for Treatment Selection

1. Assess attack severity at onset: Mild-to-moderate → NSAIDs; Moderate-to-severe → Triptans 1, 2
2. If NSAIDs fail after 2-3 attacks: Switch to triptan or add triptan to NSAID 2
3. If oral route compromised by vomiting: Use subcutaneous or intranasal sumatriptan 2
4. If triptans contraindicated (cardiovascular disease, uncontrolled hypertension): Use gepants (rimegepant, zavegepant) or DHE 2
5. If requiring IV treatment: Ketorolac 30 mg IV + metoclopramide 10 mg IV 2

Critical Pitfall: Medication-Overuse Headache

• Limit all acute medications to no more than 2 days per week to prevent medication-overuse headache, which develops with NSAIDs used ≥15 days/month or triptans used ≥10 days/month 1, 2, 4
• If acute medications are needed more frequently, initiate preventive therapy with options including angiotensin-receptor blockers (candesartan), lisinopril, topiramate, valproate, or CGRP monoclonal antibodies (eptinezumab) 1
• Preventive therapy requires 2-3 months for oral agents to demonstrate efficacy 2

Adjunctive Strategies

• Add antiemetics 20-30 minutes before analgesics to enhance absorption and provide synergistic analgesia 2
• Non-pharmacologic options including aerobic exercise, physical therapy, relaxation training, and thermal biofeedback combined with relaxation training have evidence for migraine management 1