What is the recommended use and dosage of Ubrogepant (Ubrogepant) for acute treatment of migraine with or without aura in adults, particularly those with a history of cardiovascular disease?

Ubrogepant for Acute Migraine Treatment

Recommended Use and Dosing

Ubrogepant is FDA-approved for acute treatment of migraine with or without aura in adults, including those with cardiovascular disease, as it lacks vasoconstrictor effects that contraindicate triptans. 1

Standard Dosing Regimen

• The recommended initial dose is 50 mg or 100 mg taken orally with or without food at migraine onset 1
• A second dose may be taken at least 2 hours after the initial dose if needed 1
• Maximum dose is 200 mg in a 24-hour period 1
• The safety of treating more than 8 migraines in a 30-day period has not been established 1

Position in Treatment Algorithm

The American College of Physicians recommends ubrogepant as a third-line option for moderate to severe acute episodic migraine in nonpregnant adults who do not tolerate or have inadequate response to combination therapy of a triptan plus an NSAID or acetaminophen. 2

• First-line treatment should be an NSAID or acetaminophen for mild to moderate migraine 2
• If inadequate response, add a triptan to the NSAID (or to acetaminophen when NSAIDs are contraindicated) 2
• Only after failure of triptan-NSAID combinations should CGRP antagonists like ubrogepant be considered 2, 3

Critical Advantage for Cardiovascular Disease Patients

Ubrogepant is particularly valuable for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease because it has no vasoconstrictor activity, unlike triptans which are contraindicated in these populations. 4

• Triptans are contraindicated in patients with ischemic heart disease, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 4
• Ubrogepant provides a safe alternative for these high-risk patients who cannot use triptans 4

Dosage Modifications

Drug Interactions Requiring Dose Adjustment

• Moderate CYP3A4 inhibitors (e.g., fluconazole, verapamil, cyclosporine, ciprofloxacin, fluvoxamine): Use 50 mg initial dose and avoid second dose within 24 hours 1
• Weak CYP3A4 inhibitors: Use 50 mg for both initial and second dose 1
• BCRP and/or P-gp inhibitors (e.g., quinidine, carvedilol, eltrombopag): Use 50 mg for both doses 1
• Weak or moderate CYP3A4 inducers (e.g., phenytoin, barbiturates): Use 100 mg for both doses 1

Absolute Contraindications

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole): Concomitant use is contraindicated 1
• Strong CYP3A4 inducers (rifampin, St. John's Wort): Avoid concomitant use as they significantly reduce ubrogepant exposure 1

Hepatic and Renal Impairment

• Severe hepatic impairment (Child-Pugh Class C): Use 50 mg initial dose; if needed, second 50 mg dose at least 2 hours later 1
• Severe renal impairment (CrCl 15-29 mL/min): Use 50 mg initial dose; if needed, second 50 mg dose at least 2 hours later 1
• End-stage renal disease (CrCl <15 mL/min): Avoid use 1

Efficacy Data

• Pain freedom at 2 hours was achieved in 21.2% with ubrogepant 100 mg versus 11.8% with placebo (absolute difference 9.4%, P<0.001) 5
• Absence of most bothersome symptom at 2 hours occurred in 38.9% with ubrogepant 50 mg versus 27.4% with placebo (absolute difference 11.5%, P=0.01) 6
• Approximately 1 in 5 patients achieved complete pain relief with a single dose 7

Safety Profile

• Most common adverse events are nausea (2-4%), somnolence (2-4%), and dry mouth (0.4-4%), with higher rates at the 100 mg dose 5
• Hypersensitivity reactions including anaphylaxis, dyspnea, facial or throat edema can occur minutes, hours, or days after administration; if serious hypersensitivity occurs, discontinue ubrogepant immediately 1
• Long-term safety data from 52-week trials showed treatment-related adverse events in only 10-11% of participants, with no cases of Hy's Law hepatotoxicity 8
• Unlike earlier gepants, ubrogepant is free from hepatotoxicity at therapeutic doses 7

Critical Medication Overuse Prevention

Limit ubrogepant use to no more than 8 migraine attacks per 30-day period to prevent medication overuse headache, and initiate preventive therapy if acute treatment is needed more than twice weekly. 1, 2

• The American Academy of Neurology recommends limiting all acute migraine medications to no more than 2 days per week to prevent medication overuse headache 3

Special Populations

• Pregnancy: Based on animal data, may cause fetal harm; discuss risks versus benefits 1
• Lactation: Unknown if ubrogepant passes into breast milk 1
• Pediatric: Safety and effectiveness in children not established 1

Concomitant Use with Preventive CGRP Antagonists

Ubrogepant can be safely used for acute treatment in patients taking atogepant for migraine prevention, with no new safety signals identified when used concomitantly. 9

• The TANDEM study demonstrated that ubrogepant 100 mg as needed (up to 8 attacks per 4-week interval) combined with daily atogepant 60 mg was safe and well tolerated over 12 weeks 9
• No increase in adverse events was observed with increasing ubrogepant use days 9