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Gepant

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Gepant, Oral Calcitonin Gene-Related Peptide Blocker, Oral CGRP Inhibitor, Ubrogepant, Ubrelvy, Rimegepant, Nurtec, Zavegepant, Zavzpret, Atogepant, Qulipta

  • See Also
  1. Calcitonin Gene-Related Peptide Blocker
  • Indications
  1. Acute Migraine Headache
    1. Third-line agent in acute Migraine Headaches refractory to NSAIDS and Triptans
    2. Avoid for acute Migraines if also using Injectable CGRP Inhibitor for Migraine Prophylaxis
    3. Avoid using in combination with Triptans (no evidence of benefit)
  2. Migraine Prophylaxis
    1. Rimegepant (Nurtec) is FDA approved for Migraine Prophylaxis in 2021 (third-line agent)
    2. Injectable CGRP Inhibitors are also indicated in Migraine Prophylaxis
  • Mechanism
  1. Calcitonin Gene-Related Peptide (CGRP)
    1. CGRP is a neuropeptide that acts as a vasodilator and pain sensitization
    2. CGRP Is released by trigeminal Neurons in Migraine Headache, Cluster Headache and Trigeminal Neuralgia
  2. CGRP Inhibitors block CalcitoninGene-Related Peptide (CGRP)
    1. Gepants are oral or intranasal agents that block CGRP
    2. Contrast with CGRP Monoclonal Antibody agents that are injectable
  • Preparations
  1. Ubrogepant (Ubrelvy)
    1. Dose: 50 to 100 mg orally with or without food
      1. May repeat a second dose 2 hours after first)
      2. Maximum: 200 mg/24 hours
    2. Costs $85 per tablet (contrast with 70 cents per Sumatriptan tablet)
    3. May be repeated 2 hours after first dose if inadequate effect
    4. Resources: DailyMed
      1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd9f9458-fd96-4688-be3f-f77b3d1af6ab
  2. Rimegepant (Nurtec)
    1. Migraine Abortive Treatment
      1. Dissolving oral tablet: 75 mg taken as single dose (maximum 75 mg/day)
    2. Migraine Prophylaxis
      1. Dissolving oral tablet: 75 mg taken every OTHER day (maximum 18 days per month)
      2. Breakthrough acute Migraine Headache should not be treated with Rimegepant
        1. Use another type of Migraine Abortive Treatment
      3. Cost: $1800/month (contrast with $630/month for Injectable CGRP Inhibitors)
    3. Resources: DailyMed
      1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9ef08e09-1098-35cc-e053-2a95a90a3e1d&version=19
  3. Zavegepant (Zavzpret)
    1. Intranasal Gepant (useful when Nausea, Vomiting interferes with taking medication)
    2. Migraine Abortive Treatment Dosing
      1. One spray (10 mg/spray) intranasal per 24 hours as needed
    3. Pharmacokinetics
      1. Onset: 15 minutes
      2. Peak: 30 minutes
      3. Half-Life: 6.5 hours
    4. Adverse Effects
      1. Dysgeusia or Ageusia
      2. Nausea or Vomiting
      3. Nasal discomfort
    5. Safety
      1. Has not been studied in pregnancy, children, liver or renal Impairment
    6. References
      1. Lipton (2023) Lancet Neurol 22(3): 209-217 [PubMed]
  4. Atogepant (Qulipta)
    1. Migraine Prophylaxis
      1. Start 10 mg orally daily (maximum dose 60 mg/day)
      2. Adjust dose for CYP3A4 inhibitors and inducers, as well as OATP Inhibitors
    2. Resources: DailyMed
      1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8c8ab8f4-32bd-497a-befa-70c8a51d8d52
  • Efficacy
  1. Migraine Abortive Treatment (less effective than Triptans)
    1. NNT 10 for one patient to be pain free at 2 hours
    2. Contrast with the more effective and less expensive Triptans
      1. Sumatriptan NNT 5
      2. Cost of Gepants (>$100/dose) in 2024 is as much as 100 fold more than Triptans
  2. Migraine Prophylaxis
    1. Rimegepant prevents 1 Migraine more than Placebo per month in those with 10 Migraines/month on average
    2. Similar efficacy to other Migraine Prophylaxis agents including Injectable CGRP Inhibitors
  • Adverse Effects
  1. Nausea
  2. Somnolence
  3. Dry Mouth
  • Drug Interactions
  1. CYP3A4 Agents
    1. Drug levels may be increased by strong CYP3A4 inhibitors
    2. Drug levels may be decreased by CYP3A4 inducers (e.g. Phenytoin, Rifampin, St. John's Wort)
  • References
  1. (2024) Presc Lett 31(2): 9-10
  2. (2020) Presc Lett 27(3): 13
  3. (2021) Presc Lett 28(8): 43-4
  4. LoVecchio (2020) Crit Dec Emerg Med 34(2):28
  5. LoVecchio (2023) Crit Dec Emerg Med 37(5):32