Identification
- Summary
Atogepant is an oral CGRP antagonist used for the preventative therapy of episodic migraine headaches.
- Brand Names
- Qulipta
- Generic Name
- Atogepant
- DrugBank Accession Number
- DB16098
- Background
Atogepant is an oral antagonist of calcitonin gene-related peptide (CGRP) receptors indicated for the prevention of episodic migraine headaches. It was developed by AbbVie and received FDA approval under the brand name Qulipta in September 2021.7 While its approval was predated by two other members of the same drug family, namely ubrogepant and rimegepant, these agents are indicated only for abortive migraine therapy - atogepant is novel in that it is the first and only oral CGRP antagonist approved for preventative use in migraine.7 In December 2022, atogepant received Health Canada approval for the prevention of episodic migraine in adults.8 It also received approval for preventive treatment of adult migraine by the EMA in August 2023.12
In patients requiring preventative migraine therapy, current practice guidelines recommend the use of certain anti-epileptic medications (e.g. valproic acid or topiramate) or beta-blockers (e.g. propranolol), all of which can be associated with significant adverse effects.5 The "gepants" family of drugs, including atogepant, are comparatively well-tolerated1,6 and may provide a desirable treatment option for patients struggling with adverse reactions to other preventative therapies.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Atogepant (DB16098)
- Weight
- Average: 603.525
Monoisotopic: 603.170508599 - Chemical Formula
- C29H23F6N5O3
- Synonyms
- Atogepant
- External IDs
- AGN-241689
- MK-8031
Pharmacology
- Indication
Atogepant is indicated for the preventive treatment of migraine in adults by the FDA, EMA, and Health Canada.9,10,11
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 Prevention of Episodic migraine •••••••••••• ••••• •••••• Prophylaxis of Migraine •••••••••••• ••••• •• ••••• • •••••••• •••• ••• ••••• •••••• Prevention of Migraine •••••••••••• ••••• •••••• - 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
Atogepant helps to prevent migraine headaches by antagonizing the activity of a pronociceptive molecule (CGRP) which has been implicated in migraine pathophysiology.6 Intended for preventative use, rather than abortive migraine therapy, atogepant is administered once daily.6
While no dose adjustments are required for patients with mild or moderate hepatic impairment, atogepant should be avoided in patients with severe hepatic impairment. Similarly, no dose adjustments are required for patients with mild or moderate renal impairment, but patients with severe renal impairment should be limited to a maximum daily dose of 10mg.6
- 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.1 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).1 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).1
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.2
Atogepant is an antagonist of the calcitonin gene-related peptide receptor6 - it competes with CGRP for occupancy at these receptors, preventing the actions of CGRP and its ability to induce and perpetuate migraine headache pain.
Target Actions Organism ACalcitonin gene-related peptide type 1 receptor antagonistHumans - Absorption
The time to peak plasma concentration following oral administration is approximately 2-3 hours.6 Atogepant displays dose-proportional pharmacokinetics up to approximately 3-fold its recommended maximum dosage, and its pharmacokinetics are not significantly influenced by co-administration with food.6
- Volume of distribution
The mean apparent volume of distribution of atogepant is 292 L.6
- Protein binding
Atogepant is extensively (~95.3%) protein-bound in plasma.6
- Metabolism
The metabolism of atogepant is mediated primarily via CYP3A4.6 The most prevalent circulating compounds in plasma are atogepant itself and a glucuronide conjugate metabolite (M23),6 comprising approximately 75% and 15% of the administered dose, respectively,3 with at least 10 other metabolites detected in feces representing <10% of the administered dose.
- Route of elimination
The elimination of atogepant occurs primarily via metabolism by CYP3A4.6 Following a single oral dose of radiolabeled atogepant to healthy male subjects, 42% of the administered dose was recovered as unchanged parent drug in the feces and 5% as unchanged parent drug in the urine.6 In total, approximately 81% of the radioactivity was recovered in the feces, with only 8% recovered in the urine.3
- Half-life
The elimination half-life of atogepant following oral administration is approximately 11 hours.6
- Clearance
The mean apparent oral clearance of atogepant is approximately 19 L/h.6
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
There are no data regarding overdosage with atogepant. Symptoms of atogepant overdose are likely to be consistent with its adverse effect profile and may therefore include significant gastrointestinal effects, such as nausea and constipation, as well as fatigue and somnolence.6 A single oral dose of 300mg (5x the maximum recommended dose) did not result in any serious adverse events and did not appear to impact cardiac function.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Atogepant can be increased when it is combined with Abametapir. Acetylcysteine The serum concentration of Atogepant can be increased when it is combined with Acetylcysteine. Aminohippuric acid The serum concentration of Atogepant can be increased when it is combined with Aminohippuric acid. Amiodarone The serum concentration of Atogepant can be increased when it is combined with Amiodarone. Amprenavir The serum concentration of Atogepant can be increased when it is combined with Amprenavir. - Food Interactions
- Take with or without food. Co-administration with food does not affect the pharmacokinetics of atogepant 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.- International/Other Brands
- Qulipta (AbbVie)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aquipta Tablet 10 mg Oral Abb Vie Deutschland Gmb H & Co. Kg 2023-08-30 Not applicable EU 
Aquipta Tablet 60 mg Oral Abb Vie Deutschland Gmb H & Co. Kg 2023-08-30 Not applicable EU Aquipta Tablet 10 mg Oral Abb Vie Deutschland Gmb H & Co. Kg 2023-08-30 Not applicable EU Aquipta Tablet 60 mg Oral Abb Vie Deutschland Gmb H & Co. Kg 2023-08-30 Not applicable EU Qulipta Tablet 30 mg Oral Abbvie 2023-02-23 Not applicable Canada 
Categories
- ATC Codes
- N02CD07 — Atogepant
- Drug Categories
- Analgesics
- Antimigraine Preparations
- BCRP/ABCG2 Substrates
- Calcitonin Gene-Related Peptide (CGRP) Antagonists
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- MATE 1 Inhibitors
- MATE inhibitors
- Nervous System
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 inhibitors
- OATP1B3 substrates
- OCT1 inhibitors
- P-glycoprotein substrates
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 7CRV8RR151
- CAS number
- 1374248-81-3
- InChI Key
- QIVUCLWGARAQIO-OLIXTKCUSA-N
- InChI
- InChI=1S/C29H23F6N5O3/c1-13-16(22-18(30)4-5-19(31)23(22)32)8-20(26(42)40(13)12-29(33,34)35)38-25(41)15-7-14-9-28(10-21(14)37-11-15)17-3-2-6-36-24(17)39-27(28)43/h2-7,11,13,16,20H,8-10,12H2,1H3,(H,38,41)(H,36,39,43)/t13-,16-,20+,28+/m1/s1
- IUPAC Name
- (6S)-N-[(3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)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=C4C=CC=N2)C(=O)N1CC(F)(F)F)C1=C(F)C(F)=CC=C1F
References
- General References
- 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]
- Rowe J, Chan H, Chandrasekar P, Rojo J, Boinpally R: Mass Balance and Metabolism of Carbon-14 Atogepant in Healthy Male Participants. Neurology. 2021 April 13;96(15):Supplement 1425. [Article]
- Boinpally R, McNamee B, Yao L, Butler M, McGeeney D, Borbridge L, Periclou A: A Single Supratherapeutic Dose of Atogepant Does Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized, Single-Dose, Phase 1 Crossover Trial. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1099-1107. doi: 10.1002/cpdd.940. Epub 2021 May 4. [Article]
- Ha H, Gonzalez A: Migraine Headache Prophylaxis. Am Fam Physician. 2019 Jan 1;99(1):17-24. [Article]
- FDA Approved Drug Products: Qulipta (atogepant) tablets for oral use [Link]
- PR Newswire: FDA Approves QULIPTA™ (atogepant), the First and Only Oral CGRP Receptor Antagonist Specifically Developed for the Preventive Treatment of Migraine [Link]
- Cision Newswire: QULIPTA™ Now Approved by Health Canada for the Preventive Treatment of Episodic Migraine in Adults [Link]
- Health Canada Product Monograph: Qulipta (atogepant) tablets for oral use [Link]
- FDA Approved Drug Products: QULIPTA (atogepant) tablets, for oral use (April 2023) [Link]
- EMA Approved Drug Products: AQULIPTA (atogepant) tablets, for oral use [Link]
- AbbVie Announces European Commission Approval of AQUIPTA® (atogepant) for the Preventive Treatment of Migraine in Adults [Link]
- External Links
- ChemSpider
- 59718640
- BindingDB
- 362044
- 2571813
- ChEMBL
- CHEMBL3991065
- Wikipedia
- Atogepant
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Episodic Migraine 1 3 Active Not Recruiting Treatment Chronic Migraine / Episodic Migraine 2 3 Completed Prevention Chronic Migraine 1 3 Completed Prevention Episodic Migraine 1 3 Completed Treatment Chronic Migraine 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 10 mg/1 Tablet Oral 10 mg Tablet Oral 30 mg/1 Tablet Oral 30 mg Tablet Oral 60 mg/1 Tablet Oral 60 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10117836 No 2018-11-06 2035-01-30 US 
US9499545 No 2016-11-22 2031-11-10 US US8754096 No 2014-06-17 2032-07-19 US US9850246 No 2017-12-26 2033-03-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Practically insoluble in water https://www.rxabbvie.com/pdf/qulipta_pi.pdf - Predicted Properties
Property Value Source Water Solubility 0.0263 mg/mL ALOGPS logP 3.62 ALOGPS logP 3.5 Chemaxon logS -4.4 ALOGPS 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 141.62 m3·mol-1 Chemaxon Polarizability 53.45 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
- FDA Approved Drug Products: Qulipta (atogepant) tablets for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: Qulipta (atogepant) tablets for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: Qulipta (atogepant) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: Qulipta (atogepant) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: Qulipta (atogepant) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: Qulipta (atogepant) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: Qulipta (atogepant) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- FDA Approved Drug Products: Qulipta (atogepant) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- FDA Approved Drug Products: Qulipta (atogepant) tablets for oral use [Link]
Drug created at December 15, 2020 18:05 / Updated at September 02, 2023 00:24