FDA Approves Atogepant As Newest CGRP Antagonist for Migraine Prevention

By Jessica Pyhtila, PharmD, BCGP, BCPS

The FDA recently approved the CGRP antagonist atogepant (Qulipta) for the prevention of episodic migraine. It joins rimegepant (Nurtec) as the only other oral CGRP antagonist approved for this indication. Injectable CGRP antagonists for migraine prevention are available and include eptinezumab (Vyepti), erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality).

Studies showed that, when compared to placebo, atogepant reduced the number of monthly migraine days by about 4 days a month.

Atogepant comes as a tablet that should be taken by mouth once daily without regard to food. The available doses of atogepant are 10 mg, 30 mg and 60 mg. At this time, the drug has no contraindications to use. That said, the drug should be avoided in pregnant patients as well as in those with hepatic impairment.

Dose adjustments should be made for certain disease states and with the coadministration of certain medications:

— Severe renal impairment: Dose should be limited to 10 mg daily

— Coadministration of a strong CYP3A4 inhibitor like darunavir or ketoconazole: 10 mg daily

— Coadministration of a moderate or strong CYP3A4 inducer like rifampin, phenytoin, St. John’s Wort or glucocorticoids: 30 or 60 mg daily

— Coadministration of OATP inhibitors like clarithromycin, gemfibrozil, or sacubitril: 10 mg or 30 mg daily

It should be noted that some drugs may fall into more than one category. For example, clarithromycin is both a CYP3A4 inhibitor and an OATP inhibitor, meaning the atogepant 10 mg dose would be most appropriate. Similarly, rifampin is both a CYP3A4 inducer and an OATP inhibitor, meaning the appropriate dose would likely be 30 mg in a patient with healthy kidneys.

Atogepant is generally well-tolerated. However, the most common side effects are nausea, constipation, and fatigue. Nausea in particular appears to be dose-dependent, with higher doses carrying a higher risk of the side effect.

References:

Food and Drug Administration. “Qulipta.” September 2021. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215206Orig1s000lbl.pdf