Ubrogepant

• Migraine
• Migraine with Aura
• Acute Migraine Treatment

Ubrogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist, known as a gepant, used for the acute treatment of migraine with or without aura in adults. It represents a novel class of migraine-specific treatments that work differently from triptans and can be used by patients who cannot take vasoconstrictive medications.

Mechanism of Action

Ubrogepant works through selective receptor antagonism:

• CGRP receptor antagonist: Competitively blocks the calcitonin gene-related peptide receptor
• Inhibits CGRP signaling: Prevents CGRP-induced vasodilation and neurogenic inflammation
• Non-vasoconstrictive: Does not cause blood vessel constriction (unlike triptans)
• Targets trigeminovascular system: Blocks pain signal transmission in migraine pathways
• Peripheral and central effects: Works at both peripheral trigeminal nerve endings and central sites

This mechanism makes ubrogepant suitable for patients with cardiovascular disease who cannot use triptans.

Available Formulations

Ubrogepant is available as oral tablets:

• 50 mg tablets
• 100 mg tablets (Ubrelvy)

Medical Uses

FDA-Approved Indication:

• Acute treatment of migraine with or without aura in adults

Ubrogepant is not indicated for preventive treatment of migraine. It provides an alternative for patients who have contraindications to triptans or who do not respond to them.

Dosing Guidelines

Adults (Acute Migraine):

• Initial dose: 50 mg or 100 mg taken as soon as migraine begins
• Second dose: May take one additional dose at least 2 hours after initial dose if needed
• Maximum: 200 mg in 24 hours

Administration:

• Take with or without food
• Swallow tablets whole with water
• Can be taken during any phase of migraine

Important Safety Information

Contraindications:

• Concomitant use with strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin)

Warnings and Precautions:

• CYP3A4 interactions: Dose adjustments needed with moderate CYP3A4 inhibitors and inducers
• Pregnancy: Limited data; use only if benefit outweighs risk
• Hepatic impairment: Avoid in severe hepatic impairment; dose adjustments for mild-moderate
• Driving: May cause somnolence; caution advised until effects known

Drug Interactions

Significant interactions due to CYP3A4 metabolism:

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir): Contraindicated; significantly increase ubrogepant exposure
• Moderate CYP3A4 inhibitors (cyclosporine, verapamil, ciprofloxacin, fluconazole, grapefruit juice): Use 50 mg initial dose; avoid second dose within 24 hours
• Strong CYP3A4 inducers (phenytoin, barbiturates, rifampin, St. John's Wort): Avoid concomitant use; decrease ubrogepant efficacy
• Weak CYP3A4 inducers (efavirenz, etravirine, modafinil): Use with caution
• CGRP monoclonal antibodies: Limited data on concomitant use; consider potential additive effects
• BCRP inhibitors: May increase ubrogepant exposure

Special Populations

• Hepatic Impairment: 50 mg initial dose in mild-moderate; avoid second dose in 24 hours; avoid use in severe impairment
• Renal Impairment: No adjustment for mild-moderate (eGFR 30-89); use 50 mg dose if eGFR 15-29; avoid second dose within 24 hours
• End-Stage Renal Disease: Avoid use; not studied
• Elderly: No dose adjustment needed based on age alone
• Pregnancy: Limited human data; animal studies showed no harm at clinically relevant exposures
• Lactation: Unknown if excreted in breast milk; consider risks and benefits
• Pediatric: Safety and efficacy not established in patients <18 years