New Drug

Cara Aldridge Young

Ubrogepant (Ubrelvy—Allergan) has received FDA approval as the first oral calcitonin gene-related peptide (CGRP) receptor antagonist for acute treatment of migraine with or without aura in adults. It is not approved for preventive treatment of migraine. The oral agent comes in 50- and 100-mg tablets.

Ubrogepant “provides a unique opportunity for relief for those in whom other acute pain-relief options are contraindicated because of drug and/or disease interactions or who have had a poor response to more traditional and often less-efficacious options,” said Jeffrey Fudin, PharmD, adjunct associate professor at Albany College of Pharmacy and Health Sciences in New York.

Migraine headache pain—often described as an intense throbbing or pulsating pain in one area of the head—can often be triggered by various factors, including stress, hormone changes, bright or flashing lights, lack of food or sleep, and diet. Additional symptoms are nausea and/or vomiting and sensitivity to light and sound.

Approximately one-third of individuals who suffer from migraine also experience aura shortly before the migraine, stated FDA in a news release. An aura can appear as flashing lights, zig-zag lines, or a temporary loss of vision.

Migraine is three times more common in women than in men and affects more than 10% of people worldwide, FDA added.

What makes this drug unique?

Ubrogepant has a “very specific and unique pharmacology” that distinguishes it from other less-targeted therapies, including 5-HT3 antagonists, vasoconstrictors such as the ergots, NSAIDs, opioids, and sedating antihistamines, Fudin noted.

“Compared with drugs like ergotamine and tryptans, which can be quite toxic, have multiple adverse effects, serious warnings, countless drug interactions, and significant safety risks,” added Fudin, “ubrogepant, at least so far, seems very well tolerated and overall has an excellent safety profile, with the only adverse events appearing to be somnolence and nausea.”

Clinical trials

Ubrogepant’s approval for acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials in which 1,439 adult patients with a history of migraine with or without aura received the approved doses to treat an ongoing migraine.

In both studies, the percentages of patients achieving pain freedom 2 hours after treatment—defined as a reduction in headache severity from moderate or severe pain to no pain—and whose most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) stopped 2 hours after treatment were significantly greater among patients receiving ubrogepant at all doses compared with those receiving placebo. Patients were allowed to take their usual acute treatment of migraine at least 2 hours after taking ubrogepant. Twenty-three percent of patients were taking a preventive medication for migraine.

Nausea, tiredness, and dry mouth were the most common adverse effects reported by patients.

Counseling tips

Because ubrogepant is contraindicated with strong CYP3A4 inhibitors (such as clarithromycin), which can elevate ubrogepant blood levels, Fudin said it’s most important to instruct patients not to start any new medications or natural supplements without first informing them or their doctor. Pharmacists should also tell patients to inform their physician if they consume grapefruit juice, another strong CYP3A4 inhibitor, because a dosage modification of ubrogepant would be required.

“From a practical standpoint, however, CYP inhibition takes 48 hours, so by the time a new agent is started, it is likely that ubrogepant would have already been metabolized,” Fudin said.

Fudin also advised to pharmacists to warn patients about nausea and somnolence and not to operate heavy or dangerous equipment or drive immediately after taking a dose.

Pharmacists should also tell patients to notify their doctor if they become pregnant during treatment or plan to become pregnant or if they are breastfeeding or plan to breastfeed.

Ubrogepant (Ubrelvy)

Manufacturer: Allergan

Drug class: CGRP receptor antagonist

Indication: Acute treatment of migraine with or without aura in adults

Dosage: The recommended dose is 50 mg or 100 mg taken orally, as needed. If needed, a second dose may be administered at least 2 hours after the initial dose. The maximum dose in a 24-hour period is 200 mg. For patients with severe hepatic or severe renal impairment, the recommended dose is 50 mg; if needed, a second 50 mg dose may be taken at least 2 hours after the initial dose.

Of note: Data from research on animals indicate the drug may cause fetal harm. Patients with end-stage renal disease should also avoid using the drug.