What is the recommended treatment for an adult or adolescent patient with a history of migraines, who has tried other treatments without success, using Zavegepant (gepants) nasal spray?

Zavegepant Nasal Spray for Acute Migraine Treatment

Zavegepant 10 mg nasal spray should be reserved for patients who have failed or cannot tolerate the combination of a triptan plus NSAID, as it is significantly more expensive ($8,800 annually) with inferior efficacy compared to first-line combination therapy. 1

Position in Treatment Algorithm

When to Consider Zavegepant

Use zavegepant only after documented failure of:

• First-line: NSAID monotherapy (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) 1, 2
• Second-line: Triptan + NSAID combination therapy, which provides 130 additional patients per 1000 with sustained pain relief at 48 hours compared to monotherapy 1, 2
• Alternative triptans: Failure of one triptan does not predict failure of others; try at least 2-3 different triptans before escalating 1

Specific Clinical Scenarios for Zavegepant

Consider zavegepant as a third-line option when: 1

• Triptans are contraindicated (cardiovascular disease, uncontrolled hypertension, cerebrovascular disease, basilar or hemiplegic migraine)
• All available triptans have failed after adequate trials
• Patient cannot tolerate triptan side effects across multiple agents
• NSAIDs are contraindicated or ineffective when combined with acetaminophen

Dosing and Administration

Standard dosing protocol: 3

• Dose: 10 mg as a single spray in one nostril
• Frequency limit: Maximum 1 spray per 24 hours
• Monthly limit: Do not exceed 8 doses in 30 days (safety beyond this is unknown)
• Timing: Administer as early as possible during the attack for maximum efficacy 1, 2

Critical drug interaction: 3

• Avoid intranasal decongestants, which decrease zavegepant absorption
• If decongestant use is unavoidable, administer at least 1 hour AFTER zavegepant

Efficacy Data

Clinical trial results demonstrate modest benefit: 3, 4, 5

• Pain freedom at 2 hours: 22.5-24% with zavegepant vs 15-15.5% with placebo (absolute difference ~7-9%)
• Freedom from most bothersome symptom at 2 hours: 40-42% with zavegepant vs 31-34% with placebo (absolute difference ~8-9%)
• Median time to maximum concentration: 30 minutes 6

Comparative effectiveness shows inferiority to triptans: 1

• Zavegepant has lower likelihood of pain freedom and sustained pain relief at 48 hours compared to triptan + NSAID combination (low-certainty evidence)
• The American College of Physicians determined comparative evidence was insufficient to make a formal recommendation for zavegepant as first-line therapy

Safety Profile and Monitoring

Common adverse effects (from clinical trials): 3

• Dysgeusia (abnormal taste): 18-39% of patients
• Nasal discomfort: 3-10%
• Nausea: 4-6%
• Vomiting: 2%

Serious warnings requiring monitoring: 3

• Hypersensitivity reactions: Including anaphylaxis, facial swelling, urticaria—discontinue immediately if occurs
• Hypertension: Monitor blood pressure, especially within first 7 days; may require antihypertensive therapy or hospitalization
• Raynaud's phenomenon: Fingers/toes may become numb, cool, painful, or change color (pale→blue→red); discontinue if develops

Long-term safety data: 7

• One-year study with up to 8 doses monthly showed 6.8% discontinuation rate due to adverse events
• No deaths or treatment-related serious adverse events
• Aminotransferase elevations >3x upper limit of normal occurred in 2.6% but without concurrent bilirubin elevation (no hepatotoxicity signal)

Contraindications and Precautions

Absolute contraindications: 3

• History of hypersensitivity to zavegepant or any component

Use with caution and close monitoring in: 3

• Pre-existing hypertension
• History of Raynaud's phenomenon
• Kidney or liver impairment
• Pregnancy/breastfeeding (unknown safety; discuss risks vs benefits)

Drug interactions to avoid: 3

• OATP1B3 or NTCP inhibitors (significantly increase zavegepant exposure)
• OATP1B3 or NTCP inducers (decrease zavegepant exposure)

Cost Considerations

Zavegepant is substantially more expensive than alternatives: 1

• Annualized wholesale acquisition cost: $8,800 for intranasal spray formulation
• Compare to: Oral gepants $4,959-$5,994; intranasal DHE $1,320; generic triptans + NSAIDs <$100

The American College of Physicians explicitly recommends prescribing less costly medications when clinically appropriate, given similar net benefits among recommended treatments. 1, 2

Critical Pitfall to Avoid

Do not allow patients to use zavegepant more than 2 days per week (10 days per month) to prevent medication-overuse headache. 1, 2 If patients require acute treatment more frequently, transition immediately to preventive therapy (propranolol 80-240 mg/day, topiramate 100 mg/day, or candesartan as first-line options). 2