Ubrogepant | Powerful Treatment For Migraine That Works!
Written By Kobi Nathan, Pharm.D., M.Ed., CDP, BCGP, AGSF
Sleep Disorders
October 3, 2023

If you suffer from frequent migraines, you may be wondering what ubrogepant (Ubrelvy®) is and how it can help.

On December 23, 2019, the U.S. Food and Drug Administration (FDA) approved Ubrelvy (generic name ubrogepant – pronounced “yoo-bro-je-pant”), a prescription medication for the acute treatment of migraine with or without aura.

The medication is taken at the first sign of a migraine.

Ubrelvy is not to be taken to prevent chronic migraine.

It only works for immediate treatment because of the way it works in the brain (its mechanism of action).

I will discuss this later in this article.

It works by blocking the release of certain chemicals in the brain that are believed to cause migraine headache.

In clinical trials, UBRELVY was shown to reduce the pain of migraines within two hours for most people.

What are Migraines with Aura?

Migraines with Aura are very painful headaches that are accompanied by sensory disturbances that include changes in vision, tingling in the face or extremities (usually hands), flashes of light or extreme sensitivity to light, blind spots in certain areas of your field of vision, dizziness, muscle weakness, tinnitus or ringing in your ears, etc.

These sensory changes usually precede a migraine episode and warn the person that an attack is imminent.

Not all migraines are accompanied by aura.

Sometimes, you could just have a very severe headache.

At other times, you may experience aura without headache pain.

With the latter, we usually see it with younger children and older adults.

No one really knows why migraines develop.

Doctors and researchers believe that imbalances in brain chemicals, improper nerve signaling, and genetic factors may play a role.

One particular brain neuropeptide called calcitonin gene-related peptide, or CGRP, is thought to play a major role in the pathophysiology or cause of migraine attacks.

According to Benemei and colleagues, CGRP and serotonin are released when the trigeminovascular system is activated.

This system consists of neurons or nerve cells that send signals to the cerebral blood vessels.

So, any abnormal nerve cell signaling can result in a cascade of CGRP.

The CGRP then binds itself to its receptors in the trigeminovascular system and subsequently causes inflammation, dilation of the cerebral blood vessels, and corresponding pain.

See the figure below for a visual depiction of CGRP’s role in the trigeminovascular pathway.


the trigeminovascular system

Image Source: https://www.ubrelvyhcp.com/moa


What is ubrogepant?

Ubrogepant (Ubrelvy®) is a prescription medicine used to treat migraines.

The medication is the first of its kind and belongs to a group of drugs called CGRP receptor antagonists.

It works directly by competing with and “beating out” CGRP to bind to the CGRP receptors found at nerve endings, thereby preventing the resultant inflammation and pain from propagating.

The video below is a nice overview of Ubrelvy and how it works (its mechanism of action):


How effective is ubrogepant?

Two phase 3 randomized, double-blind, placebo-controlled (the gold standard methodology of clinical studies) multicenter trials, ACHIEVE and II, studied the safety and efficacy of ubrogepant for the acute management of a single migraine episode.

The attack had to be of moderate to severe intensity in adult patients who were migraine sufferers, with or without accompanying aura.

Additionally, the study participants had to have had two to eight migraine episodes of moderate to severe pain in the previous three months.

The demographic breakdown across both trials is as follows:

  • Mean Age: 41 years (Age range: 18-75 years)
  • Gender: 89% were female
  • Race:
    • 82% White
    • 15% Black
    • 17% Hispanic or Latino

Pain reduction with ubrogepant

In the clinical trials, 43% of participants received pain relief at 1 hour, and more than 60% achieved pain reduction at 2 hours with one 50 mg dose of Ubrelvy.

Of participants who took the 100 mg dose of Ubrelvy, 40% achieved pain reduction at 1 hour, and 61% did so at 2 hours after one dose.

Zero, sustained migraine pain with ubrogepant (Pain freedom)

In the same clinical trials, 70% of study participants (268 out of 384 participants) experienced zero migraine pain at four hours after a single dose of ubrogepant.

The table below breaks this down further with specific Ubrelvy doses and time frames:

Sustained Zero Pain with Ubrelvy

Ubrelvy 50 mgUbrelvy 100 mg
At 24 hours: 70% sustained zero migraine painAt 24 hours: 77% sustained zero migraine pain
At 48 hours: 60% sustained zero migraine painAt 48 hours: 72% sustained zero migraine pain
Pain freedom was defined as a reduction from moderate/severe headache pain to no pain.
Sustained pain freedom from 2 to 24 hours was defined as pain freedom with no administration of either rescue medication or second dose of investigational product, and with no occurrence thereafter of mild, moderate, or severe headache pain during the relevant number of hours after dosing.
Source: https://www.ubrelvyhcp.com/efficacy

Ubrogepant Dose

Ubrogepant should be taken as needed whenever you feel a migraine attack coming on.

Daily dosing is unnecessary, as it is not meant to be a preventive medication for migraine.

The recommended dosing is 50 mg or 100 mg taken orally, with or without food.

[A word of warning…DO NOT take Ubrelvy with grapefruit or grapefruit juice, as these will inhibit the breakdown of Ubrelvy in your body, causing it to rise to unsafe levels in your blood].

If the pain has not subsided two hours after the first dose, you can take a second tablet.

You should not take more than 200 mg within a 24-hour period.

The ACHIEVE I and II clinical trials did not study the safety of treating more than 8 migraines within a 30-day period.

Should you find yourself in a position where you have exhausted this limit within any given month, please call your doctor for guidance about possibly exceeding the recommended dosing frequency.

If you have severe liver or kidney disease (not end-stage kidney disease), the recommended dose is 50 mg. A second 50 mg dose may be taken after two hours if needed.

If you have end-stage renal disease requiring dialysis, avoid using Ubrelvy, since the drug is cleared by the kidneys.


Ubrelvy side effects

The most common side effects were nausea and somnolence (sleepiness).

These side effects seem to be dose-dependent, meaning they are more pronounced at higher doses.

The 50 mg dose did not elicit as much sleepiness and nausea as the 100 mg dose in the ACHIEVE I and II clinical trials.

When starting Ubrelvy for the first time, I suggest waiting until the weekend or other times per your schedule when you will not be driving or handling potentially dangerous equipment and machinery.

Safety first! – You want to know how your body responds to the medication before undertaking these tasks.

Other drugs that you may be taking can also increase your risk for sedation.

Dry mouth was rarely reported in clinical trials, and it was more pronounced in participants who took the 100 mg dose vs the 50 mg dose.

With regard to the impairment of fertility, the manufacturer states that no adverse effects on fertility or reproductive performance was seen in clinical studies.

See the table below for specific side effect numbers:


Adverse reactions occurring in at least 2% and at a frequency greater than placebo

Adverse ReactionPlacebo
(participant number=984)
(participant number=954)
UBRELVY 100 mg
(participant number=485)
Somnolence (Sleepiness)1%2%3%
Dry Mouth1%Less than 1%2%
Table includes adverse reactions from ACHIEVE I and II clinical trials.
Source: https://www.ubrelvyhcp.com/safety


No serious side effects or allergic reactions were noted in the clinical trials.

What medications interact with Ubrelvy?

Any medication that is a strong inducer or inhibitor of the CYP3A4 liver enzyme (which is responsible for the metabolism of many medications – more than 1900 drugs), can interfere with ubrogepant.

CYP3A4 inducers such as phenytoin, St. John’s Wort, steroid medications, and many more drugs can hasten the metabolism of ubrogepant, making it less likely to appropriately treat the migraine.

Conversely, strong CYP3A4 Inhibitors such as ketoconazole, itraconazole, and many other drugs can slow down the metabolism of Ubrelvy, causing it to increase to unsafe levels in the blood.

If you are prescribed ubrogepant, it will be very important for your doctor or pharmacist to conduct a very careful, thorough review of all your prescription medications, over-the-counter drugs, and supplements to ensure no significant drug interactions exist.

As such, please make sure that you tell them all medications you take, no matter how benign or “natural” they may seem to you.

Depending on the medication or supplements, your healthcare provider may adjust your Ubrelvy dose or make changes to your other medications.

Does Ubrelvy work for older adults?

The ACHIEVE I and II study investigators did not find any clinically significant differences between younger and elderly patients.

However, a point of importance needs to be noted here: Adequate data does not exist since the studies did not include many participants who were aged 65 years and over.

The results must be interpreted cautiously when considering the older adult population.

As my polypharmacy and medication safety article states, we want to use the geriatric mantra: Start Low, go Slow with the dosage. 

The prudent course of action would be to start at an initial dose of 50 mg dose, monitor closely for resolution of migraine symptoms and adverse reactions, and then increase the dose carefully.

We want to treat the migraine effectively, but not at the expense of our older loved ones’ safety.

The biggest concern here would be the sleepiness that can result from taking Ubrelvy.

A frail, older adult may be at risk for sustaining catastrophic falls, which could result in hospitalization or premature death.

Your loved one may also be taking other medications that could make them drowsy, adding to the danger.

Alcohol use can increase the risk of falls drastically too.



  • Ubrogepant is used to treat acute migraines
  • It should be taken immediately or within 4 hours of migraine onset
  • Ubrogepant isn’t used to prevent migraine
  • Many patients report complete pain relief from taking Ubrogepant
  • Possible side effects of Ubrogepant are sleepiness and nausea.
  • Ubrogepant should be used with caution if you have liver or kidney issues
  • Ubrogepant can interact with many OTC and prescription drugs and supplements – talk to your doctor!
  • Older adults should start with the 50 mg dose of Ubrogepant and watch themselves closely for sleepiness and nausea


Frequently Asked Questions (FAQs)

Is Ubrelvy a narcotic?

No, it is not. It is not habit-forming.

Can you cut Ubrelvy in half?

No, you cannot. Swallow the tablet whole. Do not crush, dissolve, chew, or break it.

How much Ubrelvy can you take in a day?

Your doctor will prescribe either 50 mg or 100 mg to take. If needed, you can take a second dose at least 2 hours after the first dose. However, the maximum dose is 200 mg in a 24-hour period.

Does Ubrelvy treat tension headaches?

It is not known. Ubrelvy was developed to block CGRP, a neuro-protein that is associated with causing migraines.

Can Ubrelvy cause rebound migraine?

It does not seem to be the case. While other migraine medications, such as triptans, can cause rebound headaches, clinical studies looking at Ubrelvy did not show medication overuse headache (MOH) as a side effect.

Does Ubrelvy cause weight gain or weight loss?

Weight gain or weight loss have not been reported as side effects in clinical studies.

Can you mix Ubrelvy with other pain medications, such as acetaminophen and NSAIDs (Ibuprofen, Naproxen, etc.)?

While there are no known drug interactions between Ubrelvy and the common over-the-counter pain medications, you should consult your doctor before combining them.

This is because you may have underlying medical conditions, such as liver and kidney impairment, that may be worsened by taking these medications.

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