Rimegepant

• Migraine with Aura
• Migraine without Aura
• Episodic Migraine Prevention
• Acute Migraine Treatment

Rimegepant is a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) used for both acute treatment of migraine and preventive treatment in adults. It offers a targeted approach to migraine management without the cardiovascular concerns of triptans.

Mechanism of Action

Rimegepant works by targeting the CGRP pathway:

• CGRP receptor antagonist: Competitively blocks CGRP binding to its receptor
• Inhibits trigeminovascular activation: CGRP is released during migraine attacks and causes vasodilation and neurogenic inflammation
• Central and peripheral effects: Blocks CGRP signaling in trigeminal ganglion and central pain pathways
• No vasoconstrictor activity: Safe for patients with cardiovascular disease

CGRP is elevated during migraine attacks and plays a key role in migraine pathophysiology.

Available Formulations

Rimegepant is available as:

• Orally disintegrating tablets (ODT): 75 mg (Nurtec ODT)

ODT dissolves on the tongue without water and should not be pushed through the blister pack.

Medical Uses

FDA-Approved Indications:

• Acute treatment of migraine with or without aura in adults
• Preventive treatment of episodic migraine in adults

It is the first CGRP receptor antagonist approved for both acute and preventive treatment.

Dosing Guidelines

Acute Treatment:

• 75 mg as needed
• Maximum: 75 mg per day
• Safety of treating more than 18 migraines in a 30-day period has not been established

Preventive Treatment:

• 75 mg every other day

Administration:

• Place on or under the tongue
• Allow to dissolve (typically within seconds)
• Can be taken with or without food
• Do not take with liquids

Important Safety Information

Contraindications:

• History of hypersensitivity reaction to rimegepant

Warnings and Precautions:

• Hypersensitivity reactions: Dyspnea, rash, and urticaria have occurred; may occur days after administration
• Delayed serious hypersensitivity: Severe hypersensitivity reactions can occur even with prior tolerance

Hepatic Considerations:

• Avoid in patients with severe hepatic impairment

Drug Interactions

Strong CYP3A4 Inhibitors (ketoconazole, itraconazole, clarithromycin):

• Avoid concurrent use or limit to single dose within 48 hours

Moderate CYP3A4 Inhibitors:

• Avoid another dose within 48 hours

Strong or Moderate CYP3A4 Inducers (rifampin, phenobarbital, St. John's Wort):

• Avoid concurrent use (reduces rimegepant efficacy)

P-gp and BCRP Inhibitors:

• Avoid concurrent use or limit to single dose within 48 hours

Special Populations

• Hepatic Impairment:
  • Mild to moderate: No adjustment needed
  • Severe: Avoid use
• Renal Impairment:
  • Mild to moderate: No adjustment
  • Severe/ESRD: Avoid use (not studied)
• Pregnancy: Limited data; use only if benefit outweighs risk
• Lactation: Unknown if excreted in milk
• Elderly: No dose adjustment needed