Ubrelvy: Treatment for Acute Migraines With or Without Aura in Adults

Migraines are a type of recurring headache that are usually characterized by throbbing, severe pain.¹ Migraines are believed to be genetic with triggers that can exacerbate the condition.

Some common triggers include stress, anxiety, loud noises, strong smells, hormonal changes, sudden changes in weather, too much or not enough sleep.¹ Each person is affected differently and has triggers unique to them as individuals.

Currently, there is no cure for migraines, with treatment focusing on relieving symptoms and preventing future attacks. Some of these current treatments include triptan drugs, ergotamine drugs, and pain relievers.¹

On December 23, 2019, the FDA approved ubrogepant (Ubrelvy, Allergan) to treat acute migraines with or without aura in adults.² The approval was based on 2 clinical trials that resulted in patients achieving a significantly greater reduction in headache pain compared with placebo.

Ubrelvy works as a calcitonin gene-related peptide receptor (CGRP) antagonist.² CGRP is a protein known to be released during migraine attacks and ubrogepant reduces its activity by preventing CGRP from binding to its receptors. Unlike triptan medications, it works without constricting blood vessels, which gives it a low risk of medication overuse.²

Clinical Trials

The efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine was evaluated in 2 phase 3 clinical trials (ACHIEVE I and ACHIEVE II). Both trials were randomized, double-blind, and placebo-controlled.³

The primary outcome for both trials was pain freedom and absence of most bothersome migraine-associated symptom (MBS) within 2 hours after initial dose. The secondary outcomes were sustained pain relief from 2 to 24 hours after initial dose, as well as absence of photophobia, phonophobia, and nausea from 2 hours after initial dose.³

Patients included in the study had to have at least a 1-year history of migraine with or without aura consistent with a diagnosis. Patients also had to have migraine onset before 50 years of age with migraines that typically last between 4 and 72 hours and occurring 2 to 8 times a month with moderate/severe headache pain.³

ACHIEVE I included 1672 participants who were categorized into 3 different groups: 559 participants were given placebo, 556 were given ubrogepant 50 mg, and 557 were given ubrogepant 100 mg.³ The patients were instructed to take the study medication to treat a migraine with moderate to severe headache pain intensity. A second dose of the medication was allowed within 2 to 48 hours after the initial treatment for non-responding migraines.³

ACHIEVE II included 1686 participants who were also categorized into 3 different groups; however, the study included ubrogepant 25 mg instead of the 100 mg used in ACHIEVE I.³ The participants were given the same instructions as indicated in the first study.

In both studies, the percentage of patients achieving headache pain freedom and absence of the most bothersome migraine-associated symptom 2 hours after the first dose was significantly greater than those taking placebo. The MBS most commonly reported was photophobia (56%), phonophobia (24%), and nausea (19%).³

The study proved the reduction of photophobia and phonophobia following the administration of both doses (50 mg and 100 mg) compared with placebo.

Dosing information

Dosage form: 50 mg and 100 mg oral tablets

Adults: Recommended dose is 50 mg or 100 mg taken orally with or without food. A second dose may be taken 2 hours after initial dose. Maximum dose in a 24-hour period is 200 mg.

Contraindications/Warnings and Precautions

Ubrelvy is contraindicated for use with strong CYP3A4 inhibitors. Concomitant use will result in a significant increase of ubrogepant exposure.⁴ Therefore, ubrogepant should not be taken with ketoconazole, itraconazole, clarithromycin, etc.

Ubrogepant is a renally cleared drug, therefore, use should be avoided in patients with end-stage renal disease.⁴

Interactions

Strong CYP3A4 inhibitors: co-administration is contraindicated (eg, ketoconazole).

Moderate/weak CYP3A4 inhibitors: dose adjustment recommended with concomitant use (eg, verapamil).

Strong CYP3A4 inducers: co-administration should be avoided (eg, rifampin).

Moderate/weak CYP3A4 inducers: dose adjustment recommended with concomitant use.

BCRP and/or P-gp only inhibitors: dose adjustment recommended with concomitant use (eg, carvedilol).

Adverse Events (AEs)

The most commonly reported AEs in patients include nausea and somnolence.¹ Patients may also experience less common symptoms, such as dry mouth.

Use in Special Populations

Pregnancy: There are no adequate data on the developmental risk associated with the use of ubrogepant in pregnant women. In animal studies, AEs on embryofetal development were observed following administration of ubrogepant at doses greater than those used clinically.⁴ These doses were associated with maternal toxicity.

Data suggest that women with migraine may be at an increased risk of preeclampsia and gestational hypertension during pregnancy.

Lactation: There are no data available on the presence of ubrogepant in human milk or the effects it has on the receiving infant. In animal studies, lactating rats presented with levels of ubrogepant in milk comparable to peak plasma concentrations.⁴

Pediatric use: Safety and efficacy in pediatric patients have not been established

Geriatric use: No clinically significant differences were observed between elderly and younger patients. However, clinical studies of Ubrelvy did not include a sufficient amount of participants aged 65 years and over to determine the difference in response for the geriatric population. Due to the lack of data, dose selection should be chosen with caution, starting at the lower end of the dosing range.

Hepatic Impairment: Dose adjustments are recommended for patients with severe hepatic impairment (Child-Pugh Class C).⁴ No dose adjustments are recommended for patients with mild or moderate hepatic impairment.

Renal Impairment: The renal route plays a minor role in the clearance of ubrogepant. Dose adjustments are recommended for patients with severe renal impairment.⁴ No dose adjustments are recommended for patients with mild or moderate renal impairment.

Storage and Handling

Ubrelvy should be stored between 68 and 77 degrees Fahrenheit (room temperature).⁴

About the Author

Michelle Putney is a PharmD candidate at Duquesne University’s School of Pharmacy, anticipate to graduate in Spring 2021.

Jonathan Ogurchak, PharmD, CSP, is the CEO and Co-Founder of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.