What is the next step if Nurtec (rimegepant) is not effective for migraine treatment?

Next Steps When Nurtec (Rimegepant) Fails

If Nurtec (rimegepant) is not providing adequate relief for acute migraine treatment, the next step is to combine a triptan with an NSAID (such as sumatriptan 50-100 mg plus naproxen sodium 500 mg), which represents the most effective acute treatment strategy and should be taken early in the attack while pain is still mild. 1, 2, 3

Immediate Treatment Adjustments

Optimize Current Rimegepant Use First

Before abandoning rimegepant entirely, ensure you are:

• Taking it early in the headache phase while pain is still mild, as late administration significantly reduces response rates 1, 2, 3
• Using it for the appropriate indication (rimegepant is FDA-approved for both acute treatment and prevention when taken every other day) 4, 5
• Not overusing acute medications (≥10 days/month creates medication overuse headache) 1, 6

Escalate to Triptan + NSAID Combination

The combination of a triptan with an NSAID is superior to either agent alone and represents the strongest evidence-based recommendation for moderate to severe migraine. 1, 2, 3

Specifically:

• Sumatriptan 50-100 mg PLUS naproxen sodium 500 mg produces 130 additional patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 3
• This combination should be your next step if rimegepant alone is insufficient 1, 2
• Take early in the attack for maximum effectiveness 1, 2

If One Triptan Fails, Try Another

Failure of one triptan does not predict failure of others within the class. 3, 7

Available triptans include:

• Sumatriptan, rizatriptan, eletriptan, zolmitriptan, almotriptan, frovatriptan, or naratriptan 1, 2
• Consider non-oral routes (subcutaneous, intranasal) if severe nausea/vomiting is present 2, 6

Alternative CGRP Antagonists (Gepants)

If rimegepant specifically is not working, consider other gepants:

• Ubrogepant or zavegepant (intranasal) are alternative CGRP antagonists 1, 2
• These remain third-line options after triptan + NSAID combination failure 1, 2

Fourth-Line Option: Lasmiditan

Lasmiditan (a ditan) should be reserved for patients who do not tolerate or have inadequate response to all other treatments including triptan + NSAID combinations and other gepants. 1

Critical caveat:

• Patients cannot operate machinery for at least 8 hours after intake due to driving impairment 1

Preventive Therapy Consideration

If you are treating frequent attacks (≥2 migraine days per month with significant disability), you need preventive therapy in addition to optimizing acute treatment. 1, 2, 6

First-line preventive options:

• Propranolol 80-240 mg/day or timolol 20-30 mg/day 6, 3
• Topiramate (requires 2-3 months for efficacy assessment) 6, 3
• Amitriptyline 30-150 mg/day (especially if mixed migraine and tension headache) 6, 3
• OnabotulinumtoxinA for chronic migraine (≥15 headache days/month) 6, 3

Note: Rimegepant 75 mg every other day is also FDA-approved for migraine prevention and may be more effective than acute use alone 4, 8, 5

Critical Pitfalls to Avoid

Medication Overuse Headache

Strictly limit all acute migraine medications to no more than 2 days per week. 3

• NSAIDs trigger medication overuse headache at ≥15 days/month 1, 6, 3
• Triptans and gepants trigger it at ≥10 days/month 1, 6, 3
• This creates a vicious cycle where increased medication use paradoxically worsens headache frequency 3

Medications to Absolutely Avoid

Do not use opioids or butalbital for migraine treatment. 1, 2

• These have questionable efficacy, risk of dependency, and promote medication overuse headache 1, 3
• Oral ergot alkaloids are poorly effective and potentially toxic 1

Adjunct Medications

For nausea/vomiting:

• Metoclopramide 10 mg (has direct analgesic effects through dopaminergic receptor antagonism) 1, 2, 3
• Domperidone as alternative 1, 2

When to Reassess

Evaluate treatment response 2-3 months after any change in strategy, then every 6-12 months. 1, 6

Use headache calendars to track:

• Attack frequency (migraine days per month) 1, 6
• Attack severity and pain intensity 1, 6
• Acute medication use patterns 1, 6

If all treatments fail after thorough optimization, the diagnosis should be questioned and specialist referral is indicated. 1