What is the recommended dosage and usage of Ubrelvy (ubrogepant) for acute treatment of migraine attacks?

Ubrelvy (Ubrogepant) for Acute Migraine Treatment

Recommended Dosage

The recommended dose of Ubrelvy is 50 mg or 100 mg taken orally with or without food, with an optional second dose at least 2 hours after the initial dose if needed, not exceeding 200 mg in 24 hours. 1

Standard Dosing Protocol

• Initial dose: 50 mg or 100 mg orally 1
• Second dose (if needed): May be taken at least 2 hours after the initial dose 1
• Maximum daily dose: 200 mg in a 24-hour period 1
• Monthly limit: Safety of treating more than 8 migraines in a 30-day period has not been established 1
• Food: Can be taken with or without food 1

Place in Therapy

Ubrelvy should be reserved as a third-line option for patients who do not tolerate or have inadequate response to combination therapy of a triptan plus an NSAID or acetaminophen. 2, 3

Treatment Algorithm

• First-line: Start with NSAIDs (ibuprofen, naproxen) or acetaminophen at adequate doses 2
• Second-line: Add a triptan to an NSAID (or to acetaminophen if NSAIDs are contraindicated) if first-line therapy provides insufficient pain relief 2
• Third-line: Consider Ubrelvy (or other gepants like rimegepant or zavegepant) only after failure of or intolerance to triptan-NSAID combination therapy 2, 3
• Fourth-line: Lasmiditan is reserved for patients who fail all other treatments including gepants 2

Dosage Modifications

Drug Interactions

Dose adjustments are required when Ubrelvy is used with CYP3A4 inhibitors or inducers, and with BCRP/P-gp inhibitors. 1

• Moderate CYP3A4 inhibitors: Use 50 mg initial dose; avoid second dose within 24 hours 1
• Weak CYP3A4 inhibitors: Use 50 mg for both initial and second dose 1
• Strong CYP3A4 inhibitors: Contraindicated—do not use Ubrelvy 1
• Strong CYP3A4 inducers: Avoid concomitant use 1
• Weak/moderate CYP3A4 inducers: Use 100 mg for both initial and second dose 1
• BCRP and/or P-gp only inhibitors: Use 50 mg for both initial and second dose 1

Special Populations

Patients with severe hepatic or renal impairment require dose reduction to 50 mg. 1

• Severe hepatic impairment (Child-Pugh Class C): 50 mg initial dose; 50 mg second dose if needed 1
• Severe renal impairment (CrCl 15-29 mL/min): 50 mg initial dose; 50 mg second dose if needed 1
• End-stage renal disease (CrCl <15 mL/min): Avoid use 1

Critical Clinical Considerations

Timing of Administration

Begin treatment as soon as possible after migraine onset for optimal efficacy. 2, 3

Contraindications

Ubrelvy is contraindicated in patients with a history of serious hypersensitivity reactions (including anaphylaxis, dyspnea, facial or throat edema) and with concomitant use of strong CYP3A4 inhibitors. 1

Hypersensitivity Monitoring

Discontinue Ubrelvy immediately if serious hypersensitivity reactions occur, which can manifest within minutes, hours, or days after administration. 1

• Reactions include anaphylaxis, dyspnea, facial or throat edema, rash, urticaria, and pruritus 1
• Most reactions occurred within hours of dosing 1

Medication Overuse Headache

Monitor for medication overuse headache, defined as headache occurring ≥15 days per month for at least 3 months due to overuse of acute medication. 2

• The threshold varies by medication class (≥15 days/month for NSAIDs; ≥10 days/month for triptans) 2
• Limit treatment to no more than 8 migraines per 30-day period 1

Safety Profile

Common Adverse Events

The most common adverse events are nausea and somnolence, occurring in approximately 2-4% of patients. 1, 4

• Nausea: 2.0-4.1% 1, 4
• Somnolence: 0.4-4.1% 1, 4
• Dry mouth: 0.4-4.1% 1, 4
• These events were more frequent with the 100 mg dose 1, 4

Long-Term Safety

Long-term intermittent use over 52 weeks demonstrated a favorable safety profile with no cases of Hy's Law (drug-induced liver injury). 5

• Treatment-emergent adverse events occurred in 66-73% of participants over one year, with upper respiratory tract infection being most common (<12%) 5
• Treatment-related adverse events were reported in only 10-11% of participants 5
• Serious adverse events occurred in 2-3% of participants 5

Efficacy Data

Ubrelvy demonstrated statistically significant superiority over placebo for both pain freedom and absence of most bothersome symptom at 2 hours. 4, 6

• Pain freedom at 2 hours: 19.2-21.8% with Ubrelvy vs. 11.8-14.3% with placebo 4, 6
• Absence of most bothersome symptom at 2 hours: 37.7-38.9% with Ubrelvy vs. 27.4-27.8% with placebo 4, 6

Important Limitations

Not for Prevention

Ubrelvy is not indicated for the preventive treatment of migraine. 1, 3

Pregnancy Considerations

Based on animal data, Ubrelvy may cause fetal harm and should be avoided in pregnancy. 1

Concomitant Use with Other Gepants

Ubrelvy can be safely used concomitantly with atogepant (a preventive CGRP antagonist) without new safety signals. 7

• The combination of atogepant 60 mg daily plus ubrogepant 100 mg as needed was safe and well tolerated over 12 weeks 7
• No increase in adverse events was observed with increased frequency of ubrogepant use 7

Common Pitfalls to Avoid

• Do not use Ubrelvy as first-line therapy—always trial NSAIDs and triptan-NSAID combinations first 2, 3
• Do not exceed 200 mg in 24 hours or treat more than 8 migraines per month 1
• Do not combine with strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) 1
• Do not use in end-stage renal disease 1
• Do not use opioids or butalbital for acute migraine treatment 2