Ubrogepant - Uses, Side-effects, and Precautions

Overview

Ubrogepant is used for the treatment of migraine headaches without aura. The FDA approved Ubrogepant in December 2019. It is the first oral calcitonin gene-related peptide receptor antagonist. Many small molecule CGRP receptor antagonists were under investigation for migraines. The drugs used earlier were efficacious but had liver toxicity as a side effect. This followed the development of Ubrogepant, a hepatotoxicity-free alternative medicine. It belongs to the class of drugs called calcitonin gene-related peptide receptor antagonists. CGRP is a protein in nerve endings responsible for pain and migraines. Ubrogepant blocks this CGRP protein from attachment to the nerve endings reducing pain and migraine symptoms.

Following are the advantages of the CGRP antagonists.

• They are well tolerated and do not cause headaches from medication overuse.

• They do not have any cardiovascular risk and can be used in patients with cardiovascular disease.

• The development of Ubrogepant can mark a significance in migraine headache treatment.

What Is the Use of Ubrogepant in Specific Populations?

Pregnancy

There is no adequate data on the risk associated with using Ubrogepant in pregnant women. In animal studies, adverse effects on embryo-fetal development were noticed during the administration of Ubrogepant in pregnancy. Inform the doctor about pregnancy or plan to become pregnant. It is still not known if Ubrogepant will harm the fetus.

What Are the Clinical Considerations?

Disease-Associated Maternal and Fetal risk. Data suggests that women with migraines are at an increased risk of preeclampsia and gestational hypertension.

Lactation

There is no data available on traces of Ubrogepant in human milk, the effects on the breastfed infant, or its effects on milk production. Inform the doctor about breastfeeding or about any plan to breastfeed. It is not clear yet if Ubrogepant can be traced into breast milk.

Pediatric Use

Safety and effectiveness in child patients are not established yet.

Geriatric Use

No clinically significant differences were seen in studies available between old and young subjects.

Hepatic Impairment

In patients with pre-existing mild, moderate, or severe hepatic impairment, Ubrogepant exposure was increased by 7%, 50%, and 115%, respectively. Therefore, no dose adjustment is recommended for patients with mild or moderate hepatic impairment. Dose adjustment is advised for patients with severe hepatic impairment.

Renal Impairment

The renal route of elimination plays a minute role in the clearance. Therefore, no dose adjustment is needed in mild or moderate renal impairment cases. However, dose adjustment is necessary for patients with severe renal impairment.

Overdosage

The elimination half-life of Ubrogepant is around five to seven hours, so monitoring patients after overdose with Ubrogepant should be done for at least 24 hours.

What Is the Mechanism of Action of Ubrogepant?

• Ubrogepant treats migraine headache pain by blocking the transmitter activity involved in migraine.

• Ubrogepant belongs to calcitonin gene-related peptide receptor antagonists. Therefore, at a dose two times the maximum recommended daily dose, Ubrogepant does not prolong the QT interval.

• Following oral administration of Ubrogepant, it is absorbed with peak plasma concentrations at approximately 1.5 hours—Ubrogepant shows dose-proportional pharmacokinetics in the advised dose range.

• Dose adjustments are needed for patients with hepatic or renal insufficiency in order to avoid increased exposure, and Ubrogepant is not used in end-stage kidney disorder patients.

• The current theory of migraine pathophysiology accepts the dysfunction of the central nervous system, particularly the trigeminal ganglion, as the reason for the condition.

• Activation of the trigeminal ganglion triggers and stimulates the trigeminal afferents, which in turn project to the spinal cord and synapse on pain-sensing intracranial and extracranial structures, like the dura mater.

• Pain signals are further transmitted through second-order ascending neurons to the brainstem, hypothalamus, and thalamic nuclei, followed by the cortical regions, which include auditory, visual, and motor cortices.

• The trigeminal ganglion amplifies the migraine headache pain by activating the perivascular fibers and releasing the molecules leading to pain, like calcitonin gene-related peptide (CGRP).

• The α-isoform of CGRP, present in primary sensory neurons, is a vasodilator associated with migraine pathogenesis. CGRP levels are elevated during migraine attacks, and the levels return to normal post-treatment with triptan medications, or intravenous infusions of CGRP can trigger migraine-like headaches in some patients. Along with vasodilation, CGRP acts as a pronociceptive factor and modulates neuronal excitability and pain response.

• Ubrogepant is an antagonist of the calcitonin gene-related peptide receptor and competes with CGRP to occupy the position at these receptors, and prevents the action of CGRP and the ability of CGRP to amplify and perpetuate migraine headache, ultimately discontinuing the headache.

Pharmacodynamics of Ubrogepant:

Absorption

After oral administration, Tmax is seen between 0.7 and 1.5 h. Tmax is delayed by around two hours when consumed with a high-fat meal, and Cmax reduces by 22%. Ubrogepant has dose-related pharmacokinetics according to the recommended doses.

The Volume of Distribution

The apparent central volume of distribution after oral administration is 350 L.

Protein Binding

Ubrogepant is 87% protein-bound in vitro; however, the specific proteins to which Ubrogepant binds are unknown.

Metabolism

Ubrogepant is eliminated mainly by metabolism; the majority of metabolism is mediated by CYP3A4. Circulating glucuronide conjugates and unchanged parent drugs are commonly found in circulating components in plasma. The glucuronide metabolites carry significantly less activity at CGRP receptors and are considered inert pharmacologically.

Route of Elimination

The main route of elimination of Ubrogepant is fecal or biliary. Also, renal excretion is minimal - when followed up after administration of only one oral dose to healthy patients, around 42 % of the dose remained unchanged in the feces, and six percent was unchanged in the urine. Ubrogepant is eliminated through metabolism, primarily by CYP3A4. The parent compound Ubrogepant and two glucuronide conjugate metabolites were the prevalent circulating components in human plasma. The glucuronide metabolites, however, do not contribute to the pharmacological activity of Ubrogepant as they are less potent in the CGRP receptor binding assay.

Half-life

Ubrogepant has an elimination half-life of around five to seven hours.

Clearance

The oral clearance of Ubrogepant is around 87 L/h.

Excretion

The elimination half-life of Ubrogepant is around five to seven hours. The mean oral clearance is 87 L/hr. Ubrogepant is excreted via the biliary or fecal route, while the renal.

Effect of Food

When Ubrogepant was administered with a high-fat meal, the time to maximum Ubrogepant plasma concentration was delayed by two hours.

Distribution

The plasma protein binding of Ubrogepant is 87%. The mean central volume of distribution of Ubrogepant post-single-dose oral is 350 L.

How to Use Ubrogepant 100 MG Tablet?

• Read the patient information guide available with the medication before consuming Ubrogepant, and do the same with every refill. In case of any queries, consult the doctor or pharmacist.

• Take Ubrogepant by mouth with or without food and as directed by a doctor at the first migraine episode.

• The dosage is prescribed according to the medical condition, medication response, and other treatment options. Inform the doctor and pharmacist about all the prescription drugs, nonprescription drugs, and herbal products in use. If required, the second tablet can be taken two hours after the first one.

• The second tablet should not be taken within 24 hours after consumption of grapefruit or grapefruit juice. Do not exceed 200 milligrams in 24 hours.

• It is still unclear if Ubrogepant can be taken for more than eight migraines in 30 days.

What Are the Side Effects of Ubrogepant?

• Nausea.

• Drowsiness and sleepiness.

• Allergic reactions to this drug are rare.

• Rash, itching/swelling.

Inform the healthcare provider about the medication for the following drugs.

• Verapamil.

• Cyclosporine.

• Ciprofloxacin.

• Fluconazole.

• Fluvoxamine.

• Phenytoin.

• Barbiturates.

• Rifampin.

• Quinidine.

• Carvedilol.

• Eltrombopag.

• Curcumin.

What Precautions Are to Be Taken With Ubrogepant?

• Before taking Ubrogepant, be sure about being allergic to it or any other allergies.

• Ubrogepant contains inactive ingredients, which can cause allergic reactions.

• Inform the doctor or pharmacist about the medical history, kidney, and liver problems.

• This drug can cause drowsiness.

• Avoid driving, using machines, or doing any activity that needs alertness. Limit alcoholic beverage intake. Inform the doctor about the use of marijuana.

• Before surgery, inform the doctor about all the products, prescriptions, nonprescription, and herbal products used.

• During pregnancy, Ubrogepant should be used only when needed. Know the risks and benefits of the medication.

What Are the Interactions of Ubrogepant With Other Drugs?

• Drug interactions change how medications work or increase the risk for serious side effects.

• Other medications can affect the elimination of Ubrogepant from the body, which affects how Ubrogepant works.

• Azole antifungals, like Ketoconazole and Itraconazole.

• Macrolide antibiotics like Clarithromycin and Erythromycin.

• Rifamycins like Rifampin and Rifabutin.

• Drugs used to treat seizures like Carbamazepine and phenytoin.

Does Ubrogepant 100 MG Tablet Interact With Other Drugs?

• Call the emergency medical service if someone has overdosed and has severe symptoms such as passing out or trouble breathing.

• Certain foods, beverages, or food additives, red wine, cheese, chocolate, and monosodium glutamate, along with lifestyle patterns of irregular eating and sleeping habits, stress can trigger migraine headaches. Avoiding such "triggers" can reduce migraine episodes.

• Lab tests and medical tests, including kidney or liver function tests, should be done along with the medication.

How to Store and Dispose of Ubrogepant?

Ubrogepant can be stored at room temperature, away from light and moisture. Keep the medication away from children and pets. Do not flush down the drugs or pour them into a drain. Discard the product if expired or not needed. Dispose of the products. Keep this medication in the container that is closed tightly and out of sight and reach of kids. Storage should be at room temperature.

Prevent excessive heat and moisture. It is necessary to keep all medication out of reach of children as medications are not child-friendly, and kids can easily open them. children can be protected from poisoning by locking the safety caps and placing the medication in a safe position. Unneeded medications should be disposed of to ensure that pets, children, and nobody can consume them. However, be careful not to flush the medication down the toilet. Instead, the best way to dispose of the drug is via a medicine take-back program.

Why Is Ubrogepant Medication Prescribed?

Ubrogepant treats severe migraine headaches, throbbing headaches, nausea, and sensitivity to sound. Ubrogepant is a group of calcitonin gene-related peptide receptor antagonists. It acts by blocking the action of a natural substance in the body leading to migraine headaches. However, Ubrogepant cannot prevent migraine episodes or does not reduce the number of attacks.

How Should Ubrogepant Be Used?

Take ubrogepant precisely as your healthcare provider tells you to take it. You can take your ubrogepant tablet with or without food. Most patients can take a second tablet two hours after the first tablet, as needed. It is unknown whether taking ubrogepant for more than eight migraine headaches in 30 days is safe. Ubrogepant is available as a tablet to be taken by mouth. It is generally taken at the first instance of a migraine headache. If the symptoms improve after one dose of ubrogepant but return within 2 hours or longer, consumption of the second tablet is recommended.

Consult the doctor to know if a double amount is required. The doctor informs the patients about the maximum number of tablets safe to be consumed in 24 hours and the maximum number of migraine headaches to be treated with Ubrogepant tablets in a span of 30 days. It is recommended to follow the directions on the prescription label or package carefully. Take ubrogepant only as directed by the physician. Consult the doctor if headaches do not get better or frequently occur even after taking Ubrogepant.

You should not consume a second tablet within 24 hours after consuming grapefruit or grapefruit juice or are taking medications that may include:

• Verapamil.

• Cyclosporine.

• Ciprofloxacin.

• Fluconazole.

• Fluvoxaminefluvoxamine.

Who Should Not Take Ubrogepant?

It is advised not to take Ubrogepant if someone is currently on medicines called CYP3A4 solid inhibitors, like:

• Ketoconazole.

• Clarithromycin.

• Itraconazole.

What Are the Ingredients in Ubrogepant?

Active ingredient: Ubrogepant.

Colloidal silicon dioxide, croscarmellose sodium, mannitol, microcrystalline cellulose, polyvinylpyrrolidone vinyl acetate copolymer, sodium chloride, sodium stearyl fumarate, and vitamin E polyethylene glycol succinate.

Dosage Forms And Strengths of Ubrogepant

• Ubrogepant 50 mg is supplied as white to off-white, capsule-shaped, biconvex tablets debossed with "U50" on one side.

• Ubrogepant 100 mg is supplied as white to off-white, capsule-shaped, biconvex tablets debossed with "U100" on one side.

• Ubrogepant50 mg is supplied as white to off-white, capsule-shaped, biconvex tablets debossed with "U50" on one side in unit-dose packets.

• Each packet contains one tablet.

Review of Literature

• Ubrogepant for the treatment of migraine, a randomized control trial, was carried out by David W Dodick gave the following information. Ubrogepant is a small-molecule calcitonin gene-related peptide receptor antagonist used to treat acute migraine. A randomized trial was conducted to evaluate the efficacy, safety, and side-effect of Ubrogepant. Adults with migraine, with or without aura, were selected to receive an initial dose of placebo, 50 mg, or ubrogepant 100 mg for the treatment of a single migraine attack, along with the option to take a second dose. The efficacy was pain relief two hours after the first dose and absence of migraine-associated symptoms at two hours, pain relief at two hours followed by sustained pain relief from 2 to 24 hours, and lack of symptoms associated with migraines like photophobia, phonophobia, and nausea at 2 hours. A higher number of participants who received Ubrogepant than those who received a placebo were free from pain and most of the symptoms two hours after the dose. The commonly reported adverse effects were nausea, somnolence, and dry mouth.

• Ubrogepant: An Oral Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist for Abortive Migraine Treatment Madell Nedd conducted a study to review the pharmacology, efficacy, and safety of Ubrogepant as an abortive migraine treatment. Relevance to patient care and clinical practice: Ubrogepant is a better option for patients who cannot tolerate nonsteroidal anti-inflammatory drugs or triptan therapy due to ineffective pain relief or relative contraindications. Ubrogepant is a well-tolerated, effective migraine treatment for those who previously could not tolerate other first-line therapies.

• Efficacy of Ubrogepant in the Acute Treatment of Migraine With Mild, Moderate or Severe Pain. Richard B. Lipton conducted a study to examine the efficacy of Ubrogepant in treating migraine with mild, moderate, or severe pain. Adults with migraine were randomized into the following groups. Ubrogepant-50mg, or Ubrogepant-100mg group. They were treated for up to eight8 migraine attacks of pain intensity every four weeks. Efficacy outcomes for Ubrogepant included two-hour pain relief, freedom from associated symptoms, and disability. Considering the migraine attacks treated with moderate or severe pain, treatment with Ubrogepant during mild pain showed significantly higher rates of pain relief and relief from associated symptoms, along with the ability to achieve normal function two hours after medicine.