What is Ubrelvy (Ubrogepant)?
Ubrelvy (ubrogepant) is an oral calcitonin gene-related peptide (CGRP) receptor antagonist FDA-approved for the acute treatment of migraine attacks with or without aura in adults. 1
Mechanism of Action
Ubrogepant works by:
- Blocking CGRP receptors, which play a critical role in migraine pathophysiology
- Inhibiting the binding of CGRP peptide to its receptor, thereby reducing migraine pain and associated symptoms
- Providing a non-vasoconstrictive mechanism of action, unlike triptans 2
Clinical Efficacy
Ubrogepant has demonstrated significant efficacy in clinical trials:
- Pain freedom at 2 hours: 19.2% (50 mg) and 21.2% (100 mg) compared to 11.8% with placebo 3
- Freedom from most bothersome symptom at 2 hours: 38.6% (50 mg) and 37.7% (100 mg) compared to 27.8% with placebo 3
- Pain relief at 2 hours: 60.7% (50 mg) and 61.4% (100 mg) compared to 49.1% with placebo 1
A recent study also found ubrogepant effective when taken during the prodrome phase of migraine, with 46% of patients avoiding moderate or severe headache within 24 hours compared to 29% with placebo. 4
Available Formulations
Ubrelvy is available as:
- 50 mg oral tablets (white to off-white, capsule-shaped, debossed with "U50")
- 100 mg oral tablets (white to off-white, capsule-shaped, debossed with "U100") 1
Dosing and Administration
- Take as a single dose at the onset of migraine
- May take with or without food
- Most patients can take a second tablet 2 hours after the first if needed
- Should not take a second dose within 24 hours if consuming grapefruit/grapefruit juice or taking certain medications (verapamil, cyclosporine, etc.)
- Not recommended to take for more than 8 migraine headaches in 30 days 1
Place in Therapy
According to the 2025 American College of Physicians guidelines:
- Ubrogepant is considered for moderate to severe acute episodic migraine in patients who don't tolerate or have inadequate response to combination therapy of a triptan with an NSAID or acetaminophen 2
- It represents a newer treatment option with evidence supporting its efficacy compared to placebo, though comparative evidence with other treatments is limited 2
Safety Profile
Common adverse events (occurring in 0.4-4.1% of patients) include:
- Nausea
- Somnolence
- Dry mouth 3
In real-world studies, ubrogepant has shown high levels of patient satisfaction:
- 75.8% satisfied with relief at 2 hours
- 85.1% satisfied with ability to think clearly
- 83.8% satisfied with ability to return to normal function 5
Important Considerations
- Contraindications: Do not use with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole) 1
- Drug interactions: Dose adjustments needed with moderate CYP3A4 inhibitors (verapamil, cyclosporine, fluconazole, etc.) 1
- Pregnancy: Unknown if harmful to unborn baby; pregnancy registry available 1
- Cardiovascular advantage: Unlike triptans, ubrogepant's non-vasoconstrictive mechanism may be safer in patients with cardiovascular risk factors 2
Key Differences from Other Migraine Treatments
- Compared to triptans: Non-vasoconstrictive mechanism; potentially safer in patients with cardiovascular disease
- Compared to NSAIDs: Different mechanism of action; may be suitable for patients who cannot tolerate NSAIDs
- Compared to opioids: Recommended over opioids, which should not be used for migraine treatment 2
Ubrogepant represents an important addition to the migraine treatment arsenal, particularly for patients who have not responded to or cannot tolerate traditional first-line therapies.