Identification
- Summary
Ubrogepant is an oral CGRP antagonist used in the acute treatment of migraine with or without aura.
- Brand Names
- Ubrelvy
- Generic Name
- Ubrogepant
- DrugBank Accession Number
- DB15328
- Background
Ubrogepant is indicated for the acute treatment of migraine headaches with or without aura in adults.5 It was approved by the FDA on December 23, 2019, and is the first oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine.6 Several oral small molecule CGRP receptor antagonists, belonging to a class of medications referred to as "gepants", have been investigated for migraines, but only ubrogepant and rimegepant remain in clinical development.3,4 Previous agents within this class were efficacious but limited by liver toxicity - this led to the development of ubrogepant, which was designed to be a hepatoxicity-free alternative to its predecessors.1 Several parenteral monoclonal antibodies acting against the CGRP pathway (e.g. erenumab, fremanezumab, galcanezumab) have also been approved in recent years.3 Ubrogepant was approved by Health Canada on November 10, 2022.7
Compared to the current standard of therapy for migraine treatment, namely triptans such as sumatriptan and almotriptan, CGRP antagonists present several advantages.1 They appear to be better tolerated, do not contribute to medication overuse headaches, and carry no apparent cardiovascular risk, making them suitable for use in patients with cardiovascular disease.1 The development of oral gepants, including ubrogepant, may therefore constitute a significant advance in migraine headache treatment and may become the new standard of therapy in the treatment of this debilitating condition.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ubrogepant (DB15328)
- Weight
- Average: 549.554
Monoisotopic: 549.198774206 - Chemical Formula
- C29H26F3N5O3
- Synonyms
- Ubrogepant
- Ubrogépant
- Ubrogepantum
- External IDs
- MK-1602
Pharmacology
- Indication
Ubrogepant is indicated for the acute treatment of migraine with or without aura in adults.5,7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Migraine with aura •••••••••••• ••••• •••••• Treatment of Migraine without aura •••••••••••• ••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Ubrogepant acutely treats migraine headache pain by blocking the activity of a key transmitter involved in migraine pathogenesis.5 Exposure to ubrogepant can be significantly increased in patients with severe hepatic or renal insufficiency - dose adjustments are required for these patients in order to avoid excessive exposure, and ubrogepant is not recommended in patients with end-stage renal disease.5
- Mechanism of action
The currently accepted theory of migraine pathophysiology considers dysfunction of the central nervous system, in particular the trigeminal ganglion, to be the root cause behind the condition.3 Activation of the trigeminal ganglion triggers the stimulation of trigeminal afferents that project to the spinal cord and synapse on various pain-sensing intra- and extracranial structures, such as the dura mater. Pain signals are then further transmitted via second-order ascending neurons to the brainstem, hypothalamus, and thalamic nuclei, and from there to several cortical regions (e.g. auditory, visual, motor cortices).3 The trigeminal ganglion appears to amplify and perpetuate the migraine headache pain through the activation of perivascular fibers and the release of molecules involved in pain generation, such as calcitonin gene-related peptide (CGRP).3
The α-isoform of CGRP, expressed in primary sensory neurons, is a potent vasodilator and has been implicated in migraine pathogenesis - CGRP levels are acutely elevated during migraine attacks, return to normal following treatment with triptan medications, and intravenous infusions of CGRP have been shown to trigger migraine-like headaches in migraine patients. In addition to its vasodilatory properties, CGRP appears to be a pronociceptive factor that modulates neuronal excitability to facilitate pain responses.4
Ubrogepant is a potent antagonist of the calcitonin gene-related peptide receptor5 - it competes with CGRP for occupancy at these receptors, preventing the actions of CGRP and its ability to amplify and perpetuate migraine headache pain, ultimately terminating the headache.4
Target Actions Organism ACalcitonin gene-related peptide type 1 receptor antagonistHumans - Absorption
Following oral administration, Tmax occurs between 0.7 and 1.5 h.4,5 When administered with a high-fat meal, Tmax is delayed by approximately 2 hours and Cmax was reduced by 22% with no significant changes to the AUC.5 Ubrogepant exhibits dose-proportional pharmacokinetics throughout the entirety of its recommended dosing range.5
- Volume of distribution
The apparent central volume of distribution following oral administration is approximately 350 L.5
- Protein binding
Ubrogepant is 87% protein-bound in vitro, although the specific proteins to which ubrogepant binds have not been elucidated.5
- Metabolism
Ubrogepant is eliminated primarily via metabolism, the majority of which is mediated by CYP3A4.5 Two circulating glucuronide conjugates, along with unchanged parent drug, were found to be the most abundant circulating components in human plasma. The glucuronide metabolites reportedly carry 6000-fold less activity at CGRP receptors and are therefore considered to be pharmacologically inert.5
- Route of elimination
The main route of elimination is fecal/biliary, while renal excretion is comparatively minor - following administration of a single oral dose to healthy subjects, approximately 42% of the dose was recovered unchanged in the feces and 6% was recovered unchanged in the urine.5
- Half-life
Ubrogepant has an elimination half-life of 5-7 hours.5
- Clearance
The apparent oral clearance of ubrogepant is approximately 87 L/h.5
- Adverse Effects
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As clinical experience with ubrogepant is limited, detailed toxicity information is not readily available. Prescribing information for ubrogepant recommends a monitoring period of at least 24 hours following overdose based on its 5 to 7 hour half-life.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Ubrogepant can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Ubrogepant can be increased when it is combined with Abemaciclib. Abrocitinib The serum concentration of Ubrogepant can be increased when it is combined with Abrocitinib. Acalabrutinib The serum concentration of Ubrogepant can be increased when it is combined with Acalabrutinib. Acetaminophen The serum concentration of Ubrogepant can be increased when it is combined with Acetaminophen. - Food Interactions
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of ubrogepant.
- Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ubrelvy Tablet 100 mg/1 Oral Allergan, Inc. 2019-12-23 Not applicable US 
Ubrelvy Tablet 100 mg Oral Abbvie 2023-04-04 Not applicable Canada 
Ubrelvy Tablet 50 mg/1 Oral Allergan, Inc. 2019-12-23 Not applicable US Ubrelvy Tablet 50 mg Oral Abbvie 2023-05-11 Not applicable Canada
Categories
- ATC Codes
- N02CD04 — Ubrogepant
- Drug Categories
- Analgesics
- Antimigraine Preparations
- BCRP/ABCG2 Substrates
- Calcitonin Gene-Related Peptide (CGRP) Antagonists
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Nervous System
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 inhibitors
- OATP1B3 substrates
- OCT2 Inhibitors
- P-glycoprotein substrates
- UGT1A1 Inhibitors
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- AD0O8X2QJR
- CAS number
- 1374248-77-7
- InChI Key
- DDOOFTLHJSMHLN-ZQHRPCGSSA-N
- InChI
- InChI=1S/C29H26F3N5O3/c1-16-20(17-6-3-2-4-7-17)11-22(26(39)37(16)15-29(30,31)32)35-25(38)19-10-18-12-28(13-23(18)34-14-19)21-8-5-9-33-24(21)36-27(28)40/h2-10,14,16,20,22H,11-13,15H2,1H3,(H,35,38)(H,33,36,40)/t16-,20-,22+,28+/m1/s1
- IUPAC Name
- (6S)-N-[(3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide
- SMILES
- C[C@@H]1[C@@H](C[C@H](NC(=O)C2=CN=C3C[C@]4(CC3=C2)C(=O)NC2=NC=CC=C42)C(=O)N1CC(F)(F)F)C1=CC=CC=C1
References
- Synthesis Reference
Leonardo R. Allain, et. al., "Formulations for CGRP receptor antagonists." Australian Patent AU2014318741B2, published December 06, 2018.
- General References
- Moreno-Ajona D, Chan C, Villar-Martinez MD, Goadsby PJ: Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review. Headache. 2019 Jul;59 Suppl 2:3-19. doi: 10.1111/head.13582. [Article]
- Rubio-Beltran E, Chan KY, Danser AJ, MaassenVanDenBrink A, Edvinsson L: Characterisation of the calcitonin gene-related peptide receptor antagonists ubrogepant and atogepant in human isolated coronary, cerebral and middle meningeal arteries. Cephalalgia. 2019 Nov 1:333102419884943. doi: 10.1177/0333102419884943. [Article]
- Negro A, Martelletti P: Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019 Jun;28(6):555-567. doi: 10.1080/13543784.2019.1618830. Epub 2019 May 17. [Article]
- Martelletti P, Giamberardino MA: Advances in orally administered pharmacotherapy for the treatment of migraine. Expert Opin Pharmacother. 2019 Feb;20(2):209-218. doi: 10.1080/14656566.2018.1549223. Epub 2018 Nov 26. [Article]
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- FDA News Release: Ubrogepant approval [Link]
- Health Canada Approved Drug Products: UBRELVY (Ubrogepant) oral tablets [Link]
- FDA Approved Drug Products: Ubrelvy (ubrogepant) tablets for oral use (February 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0304882
- ChemSpider
- 28536135
- BindingDB
- 361594
- 2268216
- ChEMBL
- CHEMBL2364638
- ZINC
- ZINC000095598454
- Wikipedia
- Ubrogepant
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Episodic Migraine 1 4 Recruiting Treatment Migraine 1 4 Recruiting Treatment Migraine With Aura / Migraine Without Aura 1 3 Completed Treatment Migraine 1 3 Completed Treatment Migraine Headache, With or Without Aura 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg/1 Tablet Oral 100 mg Tablet Oral 50 mg Tablet Oral 50 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8912210 No 2014-12-16 2031-11-10 US US10117836 No 2018-11-06 2035-01-30 US US9499545 No 2016-11-22 2031-11-10 US US9833448 No 2017-12-05 2031-11-10 US US8754096 No 2014-06-17 2032-07-19 US US11717515 No 2021-12-22 2041-12-22 US US11857542 No 2021-12-22 2041-12-22 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source logP 3.07 Chemaxon pKa (Strongest Acidic) 11.74 Chemaxon pKa (Strongest Basic) 3.83 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 104.29 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 140.97 m3·mol-1 Chemaxon Polarizability 53.78 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
- Specific Function
- Adrenomedullin receptor activity
- Gene Name
- CALCRL
- Uniprot ID
- Q16602
- Uniprot Name
- Calcitonin gene-related peptide type 1 receptor
- Molecular Weight
- 52928.98 Da
References
- Blumenfeld AM, Goadsby PJ, Dodick DW, Hutchinson S, Liu C, Finnegan M, Trugman JM, Szegedi A: Efficacy of ubrogepant based on prior exposure and response to triptans: A post hoc analysis. Headache. 2021 Mar;61(3):422-429. doi: 10.1111/head.14089. Epub 2021 Mar 22. [Article]
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- FDA Approved Drug Products: Ubrelvy (ubrogepant) oral tablets [Link]
Drug created at May 20, 2019 15:15 / Updated at February 27, 2023 22:25