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

Ubrogepant Dosing and Administration for Acute Migraine Treatment

Recommended Dosage

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

• Initial dose options: 50 mg or 100 mg taken orally 1
• Second dose timing: May be taken at least 2 hours after the initial dose if needed 1
• Maximum daily dose: 200 mg within a 24-hour period 1
• Food considerations: Can be taken with or without food 1
• Frequency limitation: The safety of treating more than 8 migraines in a 30-day period has not been established 1

Dose Modifications for Specific Populations

Severe Hepatic Impairment (Child-Pugh Class C)

• Initial dose: 50 mg 1
• Second dose (if needed): 50 mg, taken at least 2 hours after the initial dose 1

Severe Renal Impairment (CrCl 15-29 mL/min)

• Initial dose: 50 mg 1
• Second dose (if needed): 50 mg, taken at least 2 hours after the initial dose 1

End-Stage Renal Disease (CrCl <15 mL/min)

• Avoid use 1

Drug Interaction Dose Modifications

Strong CYP3A4 Inhibitors

• Contraindicated: Do not use ubrogepant concomitantly with strong CYP3A4 inhibitors 1

Moderate CYP3A4 Inhibitors

• Initial dose: 50 mg 1
• Second dose: Avoid within 24 hours 1

Weak CYP3A4 Inhibitors

• Initial dose: 50 mg 1
• Second dose (if needed): 50 mg 1

Strong CYP3A4 Inducers

• Avoid concomitant use as this will result in reduction of ubrogepant exposure 1

Weak and Moderate CYP3A4 Inducers

• Initial dose: 100 mg 1
• Second dose (if needed): 100 mg 1

BCRP and/or P-gp Only Inhibitors

• Initial dose: 50 mg 1
• Second dose (if needed): 50 mg 1

Place in Therapy

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

• First-line treatment remains NSAIDs or acetaminophen for mild to moderate migraine 2
• Second-line treatment is combination therapy with a triptan plus an NSAID or acetaminophen for moderate to severe migraine 2
• Ubrogepant is considered when patients fail or cannot tolerate triptan-based combination therapy 2, 3

Critical Clinical Considerations

Timing of Administration

• Begin treatment as soon as possible after migraine onset for optimal efficacy 3
• Early administration improves treatment response rates 3

Contraindications

• History of serious hypersensitivity to ubrogepant or any component (including anaphylaxis and dyspnea, which can occur within minutes, hours, or days after administration) 1
• Concomitant use with strong CYP3A4 inhibitors 1

Medication Overuse Headache Prevention

• Limit acute medication use to no more than twice weekly to prevent medication-overuse headache 2
• If episodic migraine occurs frequently or treatment does not provide adequate response, preventive medications should be considered 2

Pregnancy and Lactation

• Based on animal data, ubrogepant may cause fetal harm 1
• Discuss adverse effects of pharmacologic treatments during pregnancy and lactation with people of childbearing potential 2

Safety Profile

Most Common Adverse Events

• Nausea and somnolence are the most common adverse events (≥2% and greater than placebo) 1
• Dry mouth was also reported in clinical trials (0.4-4.1% of patients) 4
• The 100-mg dose had higher rates of adverse events (16.3%) compared to 50 mg (9.4%) and placebo (12.8%) 4

Long-Term Safety

• Long-term intermittent use over 52 weeks demonstrated a low incidence of treatment-related adverse events and serious adverse events 5
• No cases of Hy's Law (drug-induced liver injury) were identified in long-term studies 5

Efficacy Data

Pain Freedom at 2 Hours

• 50 mg dose: 19.2-21.8% achieved pain freedom at 2 hours versus 11.8-14.3% with placebo 4, 6
• 100 mg dose: 21.2% achieved pain freedom at 2 hours versus 11.8% with placebo 4

Most Bothersome Symptom Relief

• 50 mg dose: 38.6-38.9% achieved absence of most bothersome symptom at 2 hours versus 27.4-27.8% with placebo 4, 6
• 100 mg dose: 37.7% achieved absence of most bothersome symptom at 2 hours versus 27.8% with placebo 4

Concomitant Use with Preventive CGRP Antagonists

• Ubrogepant can be safely used concomitantly with atogepant (a CGRP receptor antagonist for migraine prevention) 7
• No new safety signals were identified when ubrogepant 100 mg was used as needed with atogepant 60 mg daily for preventive treatment 7
• The safety profile remained consistent with each medication used alone 7