What is the role of Ubrelvy (Ubrogepant) in the treatment of migraine?

Ubrelvy (Ubrogepant) in the Treatment of Migraine

Ubrelvy (ubrogepant) is indicated for the acute treatment of migraine with or without aura in adults but is not indicated for preventive treatment of migraine. 1

Mechanism and Role in Treatment Algorithm

• Ubrelvy is a calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) that was FDA-approved in December 2019 as the first oral CGRP antagonist for acute migraine treatment 2
• Ubrelvy is considered a third-line medication for acute migraine treatment, after NSAIDs and triptans have failed or are contraindicated 3
• The American College of Physicians recommends considering gepants like ubrogepant for patients who do not tolerate or have inadequate response to combination therapy of a triptan and an NSAID or acetaminophen 3

Recommended Treatment Algorithm for Acute Migraine

1. First-line therapy: NSAIDs (ibuprofen, naproxen, aspirin, diclofenac) with antiemetics if needed 3
2. Second-line therapy: Triptans (sumatriptan, rizatriptan, zolmitriptan, etc.) or combination of triptans with NSAIDs 3
3. Third-line therapy: CGRP antagonists (gepants) like ubrogepant or ditans like lasmiditan 3

Efficacy and Safety of Ubrelvy

• In phase III clinical trials (ACHIEVE I and II), ubrogepant demonstrated significantly higher rates of freedom from pain at 2 hours compared to placebo (19.2% for 50 mg and 21.2% for 100 mg vs 11.8% for placebo) 4
• Ubrogepant also improved patient-reported functional disability, with significantly more patients able to function normally at 2 hours post-dose compared to placebo (40.6% for 50 mg vs 32.0% for placebo) 5
• Common adverse events include nausea (2-4%), somnolence, and dry mouth, which were generally mild and transient 4, 1
• Unlike earlier gepants, ubrogepant does not show evidence of hepatotoxicity at therapeutic doses 6

Dosing and Administration

• Available as 50 mg and 100 mg tablets 1
• Can take a second dose 2 hours after the first dose if needed 1
• Maximum dose is 200 mg within a 24-hour period 1, 6
• Should not take a second dose within 24 hours if consuming grapefruit/grapefruit juice or taking medications like verapamil, cyclosporine, ciprofloxacin, fluconazole, or fluvoxamine 1

Important Clinical Considerations

• Ubrogepant can be used with triptans if needed. A pharmacokinetic study showed no clinically significant interactions when ubrogepant was coadministered with sumatriptan 7
• Contraindicated in patients taking strong CYP3A4 inhibitors such as ketoconazole, clarithromycin, or itraconazole 1
• Not recommended for preventive treatment of migraine 1
• The CDC recommends avoiding opioids for migraine treatment, noting that triptans, NSAIDs, antiemetics, dihydroergotamine, gepants (including ubrogepant), and lasmiditan are associated with improved pain and function with usually mild and transient adverse events 3

Special Populations

• Safety in pregnancy is not well established. There is a pregnancy registry for women who take Ubrelvy 1
• Very small amounts of ubrogepant pass into breast milk; discuss with healthcare provider if planning to breastfeed 1
• Unlike triptans, gepants like ubrogepant are believed to be non-vasoconstrictive, potentially offering a safer alternative for patients with cardiovascular risk factors 3

Monitoring and Follow-up

• Document frequency, severity, and response to treatment 8
• Be aware of medication overuse headache, which can occur if acute medications are used too frequently (≥10 days/month for triptans, ≥15 days/month for NSAIDs) 3
• Consider preventive therapy if migraines occur frequently (≥2 days/month) despite optimized acute treatment 3