Rimegepant

Approved Indications:

• Acute Treatment of Migraine: For the acute treatment of migraine with or without aura in adults.
• Preventive Treatment of Episodic Migraine: Approved for preventive treatment of episodic migraine in adults (defined as having ≤14 migraine days per month).

Off-Label or Clinically Accepted Uses:

• Currently, there are no widely accepted off-label uses of Rimegepant due to its relatively recent approval and limited long-term clinical data.

Acute Migraine Treatment:

• Adults: 75 mg taken orally as a single dose, as needed.
• Maximum Dose: Do not exceed 75 mg in a 24-hour period. The safety of treating more than 15 migraine episodes in 30 days has not been established.

Preventive Migraine Treatment:

• Adults: 75 mg taken orally every other day.

Special Populations:

• Hepatic Impairment:
• Mild to moderate: No dosage adjustment required.
• Severe (Child-Pugh C): Not recommended.
• Renal Impairment:
• Mild to moderate: No dosage adjustment.
• Severe (eGFR <30 mL/min/1.73 m²): Use with caution; limited data available.
• End-stage renal disease: Not recommended.
• Elderly (≥65 years): No dosage adjustment required.

Administration Notes:

• Administer orally, with or without food.
• The orally disintegrating tablet (ODT) should be placed on or under the tongue and allowed to dissolve without water.

Rimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist. CGRP is a neuropeptide involved in the pathophysiology of migraine through vasodilation, neurogenic inflammation, and transmission of nociceptive signals. By selectively binding to the CGRP receptor, Rimegepant inhibits its activity, reducing vasodilation and pain transmission within the trigeminovascular system, thereby providing relief during acute migraine episodes and reducing the frequency of attacks with long-term use.

• Absorption: Rapidly absorbed after oral administration; time to peak plasma concentration (Tmax) is approximately 1.5 hours.
• Bioavailability: ~64% for the orally disintegrating tablet.
• Distribution: Volume of distribution: ~120 L.
• Metabolism: Primarily metabolized in the liver via CYP3A4; minor contribution from CYP2C9.
• Elimination Half-life: Approximately 11 hours.
• Excretion: ~77% in feces and ~24% in urine, mainly as metabolites.
• Food Effect: High-fat meals delay Tmax by ~1–2 hours but do not significantly affect overall exposure.

• Pregnancy: Limited data are available. Animal studies did not show teratogenicity, but human data are insufficient. Use only if clearly needed.
• Lactation: Unknown if rimegepant is excreted in human milk. Due to potential risk to the infant, caution is advised. Consider the benefits of breastfeeding and the importance of the drug to the mother.

• Primary Class: Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist
• Subclass: Gepant (oral CGRP antagonist for migraine treatment and prevention)

• Known hypersensitivity to rimegepant or any component of the formulation
• Severe hepatic impairment (Child-Pugh C)
• End-stage renal disease

• Hypersensitivity Reactions: Including dyspnea, rash, and angioedema; may occur hours to days after use.
• Hepatic and Renal Impairment: Use with caution in severe renal impairment; contraindicated in severe hepatic dysfunction.
• Drug Accumulation Risk: In cases of repeated use or impaired metabolism, increased drug exposure could enhance adverse effects.
• Monitoring: Monitor for signs of allergic reaction, especially after first dose.

Common (≥2%):

• Nausea
• Urinary tract infections

Less Common:

• Rash
• Dizziness
• Fatigue

Serious or Rare:

• Hypersensitivity reactions (including anaphylaxis and delayed-onset angioedema)
• Severe rash or mucocutaneous reactions (rare)

Onset: Usually occurs within hours after ingestion in acute use. Side effects during preventive use may appear over days to weeks.

• CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin): May increase plasma concentrations of rimegepant; avoid concurrent use.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): May reduce efficacy due to decreased plasma levels.
• P-gp and BCRP inhibitors (e.g., cyclosporine): May increase exposure; caution is advised.
• Alcohol: No direct interaction known, but may worsen migraine symptoms or increase CNS side effects.
• Enzyme System Involved: Primarily metabolized via CYP3A4; inhibitors and inducers of this enzyme significantly alter drug levels.

• FDA Approval: Rimegepant was approved by the FDA in 2020 for acute migraine treatment and in 2021 for preventive treatment of episodic migraine.
• Guidelines: The American Headache Society (AHS) has included CGRP antagonists like Rimegepant as first-line options for patients who cannot tolerate or do not respond to triptans.
• EMA: Approved for both acute and preventive migraine management in the European Union.

• Storage Temperature: Store below 30°C (86°F).
• Humidity Protection: Store in a dry place; protect from moisture.
• Light Protection: No special protection required.
• Handling Precautions: Keep in original packaging until use. Do not crush or break the ODT.
• Reconstitution: Not applicable.