What is the recommended treatment for a patient with acute migraine attacks, considering Rimegepant (Rimegepant) as a potential option?

Rimegepant for Acute Migraine Treatment

Rimegepant 75 mg is recommended as a third-line medication for acute migraine treatment, reserved for patients who have failed or cannot tolerate triptans and NSAIDs, with proven efficacy in achieving pain freedom and relief within 2 hours. 1, 2

Place in Therapy Algorithm

First-Line Treatment (Try These First)

• Start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) for mild to moderate migraine attacks 1, 3
• For moderate to severe attacks, use combination therapy: triptan (sumatriptan 50-100 mg) PLUS NSAID (naproxen 500 mg), which is superior to either agent alone 1, 3

Second-Line Treatment (When First-Line Fails)

• Try different triptans if one fails—failure of one triptan does not predict failure of others 1
• Consider subcutaneous sumatriptan 6 mg for rapid progression to peak intensity or significant vomiting 1, 3

Third-Line Treatment: Rimegepant

• Use rimegepant 75 mg ODT when all available triptans have failed after adequate trial (no or insufficient response in at least 3 consecutive attacks) OR when triptans are contraindicated 1, 4
• Rimegepant is specifically indicated for patients with documented triptan unsuitability due to intolerance, lack of efficacy, or contraindications 5

Dosing and Administration

Acute Treatment Dosing

• Take 75 mg orally disintegrating tablet (ODT) at migraine onset, as needed 2
• Maximum dose: 75 mg in any 24-hour period 2
• Do not exceed 18 doses in a 30-day period—safety beyond this frequency has not been established 2
• Place tablet on or under tongue; it dissolves without water 2

Preventive Treatment Option

• Rimegepant can also be used for preventive treatment at 75 mg every other day for episodic migraine 2
• This dual indication makes rimegepant unique as the first agent approved for both acute and preventive migraine treatment 6

Efficacy Evidence

Acute Treatment Outcomes

• Pain freedom at 2 hours: 19.6% with rimegepant vs 12.0% with placebo (number needed to treat = 13) 1
• Pain relief at 2 hours: 55.9% with rimegepant vs 32.7% with placebo in triptan-unsuitable patients 5
• Freedom from most bothersome symptom at 2 hours: statistically superior to placebo 1, 7
• Sustained pain relief from 2-48 hours: significantly better than placebo 5

Preventive Treatment Outcomes

• Mean reduction of 4.3 monthly migraine days vs 3.5 days with placebo (difference of 0.8 days, p=0.010) 2
• 49.1% achieved ≥50% reduction in moderate to severe monthly migraine days vs 41.5% with placebo 2
• Benefits sustained over 52 weeks with mean decrease of 6.2 monthly migraine days 8

Safety Profile

Common Adverse Events

• Nausea is the most common adverse event (≥1% for acute treatment; ≥2% for preventive treatment) 2
• Abdominal pain and dyspepsia occur in ≥2% with preventive use 2
• Overall adverse event rate similar to placebo (12.5% vs 12.1%) 5
• Most events are mild in severity 8

Serious Safety Considerations

• Hypersensitivity reactions can occur, including dyspnea and rash, potentially days after administration—discontinue immediately if this occurs 2
• No evidence of hepatotoxicity: no participants had ALT/AST >3× ULN concurrent with total bilirubin >2× ULN 8, 6
• No cardiovascular toxicity observed in clinical trials 6
• Serious adverse events rare (2.2% in 52-week study), none liver-related 8

Drug Interactions and Contraindications

Absolute Contraindications

• History of hypersensitivity reaction to rimegepant or any component 2

Avoid Concomitant Use

• Strong CYP3A4 inhibitors: avoid concomitant administration 2
• Moderate CYP3A4 inhibitors: avoid another dose within 48 hours 2
• Strong and moderate CYP3A inducers: avoid concomitant administration 2
• Potent P-glycoprotein inhibitors: avoid another dose within 48 hours 2

Special Populations

• Severe hepatic impairment (Child-Pugh C): avoid use due to significantly higher exposures 2
• Pregnancy: limited data available; pregnancy registry exists (call 1-877-366-0324) 2
• Breastfeeding: very small amounts pass into breast milk 2

Critical Medication-Overuse Headache Prevention

Limit rimegepant to no more than 2 days per week for acute treatment to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 3

• If requiring acute treatment more than twice weekly, initiate preventive therapy immediately 3
• The 18-dose per 30-day maximum helps enforce this frequency limitation 2
• Consider switching to preventive dosing (every other day) if frequent acute treatment is needed 2

Advantages Over Triptans

When Rimegepant is Particularly Valuable

• No cardiovascular contraindications—unlike triptans, rimegepant can be used in patients with ischemic heart disease, uncontrolled hypertension, or significant cardiovascular disease 1, 9
• No driving restrictions (unlike lasmiditan, which requires 8-hour restriction) 1
• Favorable tolerability profile with adverse event rates similar to placebo 6, 5
• Orally disintegrating formulation useful for patients with nausea 2, 6

Cost and Access Considerations

• Rimegepant is more expensive than first-line treatments (NSAIDs and triptans) 4
• Availability is currently limited compared to triptans 1
• Insurance coverage may require documentation of triptan failure or contraindication 4

Common Pitfalls to Avoid

• Do not use rimegepant as first-line therapy—always try NSAIDs and triptans first unless contraindicated 1, 4
• Do not exceed 75 mg in 24 hours or 18 doses in 30 days 2
• Do not combine with strong CYP3A4 inhibitors or inducers 2
• Do not use in severe hepatic impairment 2
• Do not allow frequent use pattern to develop—transition to preventive therapy if needed more than twice weekly 3
• Do not push tablet through foil—peel back foil and remove gently 2
• Do not store tablet outside blister pack for future use 2