Ubrogepant: The First Gepant to Pass Food and Drug Administration for Acute Migraine

Abstract

Migraine is one of the most common and disabling forms of primary headache disorders. It is characterized by the presence of unilateral pulsatile headache associated commonly with nausea, vomiting, photophobia, and phonophobia lasting for about 4–72 h. Currently, nonsteroidal anti-inflammatory drugs, ergot alkaloids, and triptans are the most commonly used drugs to abort an acute attack of migraine. Management of acute migraine is becoming a challenging task to physicians and patients due to several drawbacks faced with the use of aforementioned drugs. This lacuna is being filled up by developing drugs against novel targets such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide. In December 2019, the US Food and Drug Administration (FDA) approved ubrogepant for the treatment of acute migraine with or without aura in adults. Ubrogepant belongs to a new class of drugs called “Gepants” which are small molecules targeted against the CGRP receptor. The recommended initial dose is 50 mg or 100 mg orally. It follows first-order kinetics and is metabolized to a major extent by CYP3A4-mediated mechanisms. Compared to placebo, ubrogepant causes significant and rapid freedom from headache, pain and absence of migraine-associated most bothersome symptoms. Nausea, vomiting, and dry mouth are some of its common adverse effects. Ubrogepant with advantages such as good oral bioavailability, lack of vasoconstrictor action, and lack of hepatotoxicity might emerge as a promising drug for terminating an acute attack of migraine in the future. However, long-term clinical studies are needed to ascertain its safety profile.