Access to the PPM Journal and newsletters is FREE for clinicians.
19 Articles in Volume 20, Issue #2
20/20 with Peter Staats, MD: The Future of Pain Medicine
Ask the APP: How useful and practical are pain assessment tools?
Ask the PharmD: What are the recommendations for preventing and treating pediatric migraine?
Axial Spondyloarthritis: Updated Medication and Imaging Recommendations
CGRP Monoclonal Antibodies for Chronic Migraine Prevention: Evaluation of Adverse Effects Using A Checklist
Chronic Low Back Pain: Can We Find a Treatment Consensus?
Correspondence: Are ESIs Still Worth It? Benzocaine for Orofacial Pain.
Could Pulsed RF Provide Lasting Chronic Headache Relief in Refractory Patients?
Diagnosis Is Everything: Low Back Pain As a Symptom of an Underlying Condition or Conditions
Editorial: From Just Say No, to Say Now and Say Know
Erenumab and Onabotulinumtoxin A Show Additive Effect in Refractory Chronic Migraine
Experts Roundtable: Finding a Bottom Line in Back Pain Care
Inside the Potential of RNAi to Target the Etiology of hATTR Neuropathy
Muscle Dysfunction in Head and Neck: Pain Causes, Osteopathic Options
New Migraine Medications: Oral Gepants, Ditan Tablet, and More
Root Cause of Sacroiliac Joint Dysfunction: Four-Step Exercise Protocol
The Emotional Impact of Chronic Low Back Pain
The Rise in Tianeptine Abuse: Our Next Kratom Problem?
The Sensory Component of Pain: Modifying Its Emotional and Cognitive Meaning

New Migraine Medications: Oral Gepants, Ditan Tablet, and More

Small molecule CGRP receptor antagonists may be utilized as migraine abortives or preventive. Plus, a look at the new intravenous CGRP inhibitor and the abortive ditan tablet.
Page 53

The preventive CGRP monoclonal antibodies (Aimovig, Emgality, Ajovy) are large molecules, delivered once per month as a subcutaneous injection. Gepants, on the other hand, are small molecule CGRP receptor antagonists that may initially be utilized as migraine abortives but may also be used to prevent migraine. Several gepants, intended to be delivered orally, have been developed since 2004.1

As a natural inflammatory compound in the body, CGRP can trigger a cascade of inflammatory mediators that feed into the trigeminovascular system. By blocking CGRP, gepants aim to stop the process prior to inflammation. Gepants may be beneficial for three groups of migraineurs:

  • those who failed treatment on triptans (eg, sumatriptan, rizatriptan, zolmitriptan), or for whom a gepant will be added as an alternative to the patient’s triptan regimen
  • those unable to tolerate triptans
  • those with significant cardiac or cerebrovascular risk factors (gepants do not constrict cardiac or cranial arteries).

The Oral Gepants

Ubrogepant: The first-in-class oral CGRP antagonist to come to market is ubrogepant (Ubrelvy), approved by FDA for the acute treatment of migraine with or without aura in adults in December 2019. Approximately 2,700 patients participated in the gepant’s ACHIEVE trials,2,3 with doses ranging from 25 mg to 100 mg. The t-max is 0.7 to 1.5 hours. Approximately 20% of patients who used the 50 mg dose were pain-free after 2 hours. While 25 mg and 100 mg tablets were evaluated, it is likely that 50 mg will be the primary dose. Ubrogepant was well tolerated, with 2% to 5% of patients reporting nausea, somnolence, dry mouth, dizziness, or upper respiratory tract infections. No serious adverse events were reported in the trials. The safety and tolerability was also explored in a 52-week extension study. Few adverse events, and no serious ones, were reported. No hepatotoxicity was reported. (Of note, another gepant, telcagepant, was extensively studied but withdrawn in 2009 due to hepatotoxicity concerns.)

The effect of ubrogepant on the patients' most bothersome migraine symptom was evaluated 2 hours post-dose. Thirty-nine percent of those treated with ubrogepant reported that their worst migraine symptom was resolved. The therapeutic gain for ubrogepant (active drug compared to placebo) is relatively low, 6.4% to 9.4%.2,3 In comparison, the therapeutic gain for sumatriptan is 16% to 21%. Since ubrogepant was introduced in January 2020, early results have been encouraging. Efficacy has been reasonable, with a paucity of adverse effects.

Rimegepant: Rimegepant (Nurtec ODT) was FDA approved in February 2020 for abortive use in migraine sufferers. The dose is 75 mg, with a t-max of 2 hours. Rimegepant is indicated for one dose per day. In the two main trials, 19.4% of patients achieved pain freedom at 2 hours.4 Thirty-seven percent of patients reported freedom from their most bothersome symptom. As with ubrogepant, no significant liver toxicity was reported. Adverse events were low, with nausea being reported by 1.4% of patients. The therapeutic gain for rimegepant is 5% to 7.6%. Rimegepant is also being evaluated as a migraine preventive.

Atogepant: A third gepant, atogepant, is currently being studied for use as a migraine preventive.

Overall, the oral CGRP receptor agonists promise to be a useful alternative to triptans, which many migraine patients find to be ineffective or intolerable. The initial (2 hour) efficacy rates are fairly low, but it appears that gepants may become more effective over 2 to 8 hours. During trials, the medications were fairly well tolerated. As with the large molecules, it will take several years before the community is able to accurately assess the adverse effect profile of the gepants.

The Ditan Tablet

Lasmiditan (Reyvow) is a newly approved (October 2019) migraine abortive tablet. It is a “ditan,” that is, an antagonist at the 5-HT 1F serotonin receptor. Lasmiditan does not constrict the coronary or cerebral vessels and offers an alternative for those who cannot take the triptans. As with the gepant use, there are patients who may respond to lasmiditan, who do not do well with the triptans. Lasmiditan, available in 50- and 100-mg tablets, is a controlled (Schedule V) substance. Patients are cautioned not to drive for 8 hours after using lasmiditan. It is indicated for only one dose per day. Dizziness has been one of the prominent side effects thus far.5

An Intravenous Large Molecule CGRP mAb

Eptinezumab (Vyepti), a CGRP monoclonal preventive, was FDA approved in February 2020. Eptinezumab is the first intravenous formulation for the prevention of migraine in adults with a recommended dose of 100 mg every 3 months. Vyepti may work fairly quickly (within hours to days). In clinical trials, efficacy has been excellent.6


More on the large molecule CGRP monoclonal antibodies.

Last updated on: May 14, 2020
Continue Reading:
CGRP Monoclonal Antibodies for Chronic Migraine Prevention: Evaluation of Adverse Effects Using A Checklist
close X