Managing Migraine, Part 3: A Primer on CGRP Receptor Antagonists for Migraine

Calcitonin gene-related peptide (CGRP) antagonists are the first class of drugs developed exclusively for migraine prevention.

Calcitonin gene-related peptide (CGRP) antagonists are the first class of drugs developed exclusively for migraine prevention. CGRP is a neuropeptide in the nervous system that is released during migraine attacks, causing blood vessel dilation, inflammation, and migraine pain. CGRP inhibitors can reduce migraine frequency, the number of headache days, and medication usage.

Parenteral CGRP inhibitors are monoclonal antibodies and must be injected due to their large molecular size. Erenumab (Aimovig) works by binding to the CGRP receptor so that CGRP cannot attach to it. Fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti) all bind to the CGRP molecule, preventing it from binding to the receptor.

Erenumab-aooe (Aimovig)2,3

Erenumab-aooe is available as an auto-injector and a prefilled syringe for subcutaneous administration. It is indicated for the preventive treatment of migraine in adults, with a dosage of 70 mg or 140 mg injected subcutaneously every month. The most common side effects are injection site reactions and constipation. 

Fremanezumab-vfrm (Ajovy)4,5 

Fremanezumab-vfrm is available as an auto-injector and a prefilled syringe for subcutaneous administration and is indicated for the preventive treatment of migraine in adults. The dosage is either 225 mg subcutaneously monthly, or 675 mg subcutaneously every 3 months, administered as 3 consecutive injections of 225 mg. The most common side effects are injection site reactions. An allergic reaction to fremanezumab can occur up to 1 month after an injection. 

Galcanezumab-gnlm (Emgality)6,7 

Galcanezumab-gnlm is available as a pen injection or prefilled syringe for subcutaneous administration. Emgality is indicated for the preventive treatment of migraine and the treatment of episodic cluster headache. For migraine prevention, the dosage is 240 mg subcutaneously, administered as 2 consecutive 120 mg injections, as a loading dose, followed by 120 mg subcutaneous injections every month. The most common side effects are injection site reactions and shortness of breath. An allergic reaction to galcanezumab can occur a few days after injection. 

Eptinezumab-jjmr (Vyepti)8,9

Eptinezumab-jjmr is the only CGRP administered as an intravenous infusion. Eptinezumab is indicated for the preventive treatment of migraine in adults. The dosage is a 100 mg IV, administered over 30 minutes every 3 months. The most common side effects are injection site reactions, facial flushing, and nasopharyngitis.

Gepants are a class of CGRP antagonists that are smaller in molecular size and are dosed orally. They work by binding to CGRP receptors.1 

Rimegepant (Nurtec ODT)10,11

Rimegepant is available as an orally disintegrating tablet. It is indicated for acute treatment of migraine with or without aura in adults, and is also indicated for preventive treatment of episodic migraine in adults. The dosage for acute treatment is 75 mg by mouth once daily as needed, with a maximum dosage of 75 mg in 24 hours. The dosage for preventive treatment is 75 mg by mouth every other day. The most common side effects are nausea, abdominal pain, and indigestion. An allergic reaction may occur days after taking rimegepant.

Atogepant (Qulipta)12,13

Atogepant is available as an oral tablet. Qulipta is indicated for the preventive treatment of episodic migraine in adults. The dosage is either 10 mg, 30 mg, or 60 mg by mouth once daily. Common side effects are nausea, constipation, fatigue, decreased appetite, weight loss, and increased aspartate aminotransferase and alanine transaminase.

Ubrogepant (Ubrelvy)14,15

Ubrogepant) is available as an oral tablet and is indicated for acute treatment of migraine with or without aura in adults. Unlike rimegepant, it is not indicated for preventive treatment of migraine. The dosage is 50 mg or 100 mg taken orally. A second dose may be taken at least 2 hours later if needed, and the maximum dose is 200 mg in a 24-hours period. The most common side effects are nausea, drowsiness, and dry mouth. Patients who take ubrogepant should avoid grapefruit. 

There are no significant drug interactions for fremanezumab, galcanezumab, and eptinezumab; however, there are various drug interactions for other CGRP antagonists that should be evaluated when filling a prescription. 

Come back tomorrow for the final installment of this series on migraine management: a focus on new therapies for the treatment of acute migraine.

References

  1. Mohanty D, Lippman S. CGRP inhibitors for migraine. Innov Clin Neurosci. 2020;17(4-6):39-40.
  2. Aimovig—erenumab-aooe injection. DailyMed. Updated November 22, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b998ed05-94b0-47fd-b28f-cddd1e128fd8
  3. Aimovig (erenumab). Drug monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/809910/Aimovig/Monograph 
  4. Ajovy—fremanezumab-vfrm injection. DailyMed. Updated September 21, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e344ea-5916-4947-b6f2-4a76ccc04b6b
  5. Ajovy (fremanezumab). Drug monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/833210/Ajovy/Monograph
  6. Emgality—galcanezumab-gnlm injection, solution. DailyMed. Updated March 11, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33a147be-233a-40e8-a55e-e40936e28db0
  7. Emgality (galcanezumab). Drug monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/835210/Emgality/Monograph
  8. Vyepti—eptinezumab-jjmr injection. DailyMed. Updated December 8, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79065861-6aa5-4d1f-829f-3a6471286b36
  9. Vyepti (eptinezumab). Drug monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/916110/Vyepti/Monograph
  10. Nurtec ODT—rimegepant sulfate tablet, orally disintegrating. DailyMed. Updated December 20, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ef08e09-1098-35cc-e053-2a95a90a3e1d
  11. Nurtec ODT (rimegepant). Drug Monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/916710/Nurtec-ODT/Monograph
  12. Qulipta—atogepant tablet. DailyMed. Updated October 12, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c8ab8f4-32bd-497a-befa-70c8a51d8d52
  13. Qulipta (atogepant). Drug monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/1049810/Qulipta/Monograph
  14. Ubrelvy—ubrogepant tablet. DailyMed. Updated March 1, 2021. Accessed January 13, 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd9f9458-fd96-4688-be3f-f77b3d1af6ab
  15. Ubrelvy (ubrogepant). Drug monograph. Accessed January 13, 2022. https://online.epocrates.com/drugs/9070/Ubrelvy