Identification
- Summary
Avatrombopag is a thrombopoietin receptor agonist used pre-operatively to treat thrombocytopenia in patients with chronic liver disease and in patients with chronic refractory thrombocytopenia.
- Brand Names
- Doptelet 60 Mg Daily Dose Carton
- Generic Name
- Avatrombopag
- DrugBank Accession Number
- DB11995
- Background
Avatrombopag (Doptelet), is an orally administered, small molecule thrombopoietin receptor (c-Mpl) agonist that increases platelet number without increasing platelet activation,3,10 thereby decreasing the need for blood transfusions.10 Patients with thrombocytopenia and chronic liver disease often require platelet transfusions before surgical procedures to decrease the risk of bleeding.1 Thrombocytopenia is a common complication in patients suffering from chronic liver disease, occurring as a result of liver disease or a consequence of interferon-based antiviral therapy.18
Avatrombopag was first approved by the FDA in May 2018 for use in adults with chronic liver disease who are scheduled to undergo a procedure.14 It is administered orally as the salt form avatrombopag maleate.11 Doptelet (Avatrombopag) is the first orally administered treatment option for patients with chronic liver disease, allowing a large population of patients to avoid a platelet transfusion before a procedure by increasing platelet counts to the optimal level ≥50,000 per microliter.15
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Avatrombopag (DB11995)
- Weight
- Average: 649.65
Monoisotopic: 648.1510867 - Chemical Formula
- C29H34Cl2N6O3S2
- Synonyms
- Avatrombopag
- External IDs
- E5501
- YM-477
Pharmacology
- Indication
Indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.16 It is also indicated in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.16
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 Thrombocytopenia •••••••••••• ••••• •••••••••••• •••••••• •• • •••••••• ••••••••• •••••• Treatment of Thrombocytopenia •••••••••••• ••••• ••••••• ••••• ••••••• •••••• - 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
In a study of efficacy, avatrombopag resulted in dose and exposure-dependent elevations in platelet counts in adults.1 The onset of the platelet count increase was noted within 3 to 5 days of the start of a 5-day treatment course, with the highest level of effect measured after 10 to 13 days. Following this, platelet counts decreased gradually, returning to near baseline values at the 35-day point.16
Increased platelet activation leads to increased blood clotting, which may lead to various complications.4 Avatrombopag does not lead to increased platelet activation.10
- Mechanism of action
Avatrombopag is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist that stimulates proliferation and differentiation of megakaryocytes from bone marrow progenitor cells resulting in an increased production of platelets. Avatrombopag is not competitive with thrombopoietin for binding to the TPO receptor and has an additive pharmacological effect with TPO on platelet production.16
Avatrombopag is a thrombopoietin receptor (TPOR; MPL) agonist, with possible megakaryopoiesis stimulating activity. After administration, avatrombopag binds to and stimulates the platelet thrombopoeitin receptor (TPOR), which can lead to the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells. This process increases the production of platelets and may serve to prevent chemotherapy-induced thrombocytopenia (CIT). TPOR is classified as a cytokine receptor and as a member of the hematopoietin receptor superfamily.12
Target Actions Organism AThrombopoietin receptor agonistHumans - Absorption
Following single dosing under fasted and fed conditions, mean peak concentrations occurred at 5-8 hours and declined with a half-life of 16-18 hours in Japanese and white subjects. Administration with food did not have an effect on the rate or extent of avatrombopag absorption, however, significantly reduced pharmacokinetic variability relative to the fasting state.3
Avatrombopag showed dose-proportional pharmacokinetics after single doses from 10 mg (0.25-times the lowest approved dosage) to 80 mg (1.3-times the highest recommended dosage). Healthy subjects administered 40 mg of avatrombopag showed a geometric mean (%CV) maximal concentration (Cmax) of 166 (84%) ng/mL and area under the time-concentration curve, extrapolated to infinity (AUC0-inf) of 4198 (83%) ng.hr/mL. The pharmacokinetics of avatrombopag are similar in both healthy subjects and the chronic liver disease population.16
- Volume of distribution
Avatrombopag has an estimated mean volume of distribution (%CV) of 180 L (25%).16
- Protein binding
Avatrombopag is greater than 96% bound to human plasma proteins.16
- Metabolism
Avatrombopag is primarily metabolized by CYP2C9 and CYP3A4.16
- Route of elimination
Fecal excretion accounted for 88% of the administered dose, with 34% of the dose excreted as unchanged avatrombopag. Only 6% of the administered dose was found in urine.16
- Half-life
The mean plasma elimination half-life (%CV) of avatrombopag is approximately 19 hours (19%).16
- Clearance
The mean (%CV) of the clearance of avatrombopag is estimated to be 6.9 L/hr (29%).16
- Adverse Effects
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The most common adverse reactions reported in at least 3% of patients were pyrexia, abdominal pain, nausea, headache, fatigue, and peripheral edema.9,16 Hyponatremia was also a rare serious adverse effect of this drug, seen in only 2 patients in the treatment group .16 Adverse reactions resulting in discontinuation of this drug have been anemia, pyrexia, and myalgia.16
Atrombopag is a thrombopoietin (TPO) receptor agonist, and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease. Portal venous thrombosis occurrence has been reported in patients with chronic liver disease who are treated with TPO receptor agonists.16
- 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 Avatrombopag can be increased when it is combined with Abametapir. Abatacept The metabolism of Avatrombopag can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Avatrombopag. Acenocoumarol The metabolism of Avatrombopag can be decreased when combined with Acenocoumarol. Acetohexamide The metabolism of Avatrombopag can be decreased when combined with Acetohexamide. - Food Interactions
- Take with food.
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.- Product Ingredients
Ingredient UNII CAS InChI Key Avatrombopag maleate GDW7M2P1IS 677007-74-8 MISPBGHDNZYFNM-BTJKTKAUSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Doptelet Tablet, film coated 20 mg Oral SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2020-12-16 Not applicable EU 
Doptelet Tablet, film coated 20 mg/1 Oral AkaRx, Inc. 2018-05-23 Not applicable US 
Doptelet Tablet, film coated 20 mg Oral SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2020-12-16 Not applicable EU Doptelet Tablet, film coated 20 mg Oral SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2021-01-28 Not applicable EU Doptelet Tablet 20 mg Oral SWEDISH ORPHAN BIOVITRUM AB (PUBL) Not applicable Not applicable Canada 
Categories
- ATC Codes
- B02BX08 — Avatrombopag
- Drug Categories
- BCRP/ABCG2 Inhibitors
- Blood and Blood Forming Organs
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C8 Inducers (weak)
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (weak)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Hemostatics
- OAT3/SLC22A8 Inhibitors
- P-glycoprotein substrates
- Receptors, Thrombopoietin, agonists
- Sulfur Compounds
- Thrombopoietin Receptor Agonist
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- N-arylpiperazines
- Alternative Parents
- Nicotinamides / Piperidinecarboxylic acids / Dialkylarylamines / 2,4,5-trisubstituted thiazoles / Cyclohexylamines / Aminopyridines and derivatives / N-alkylpiperazines / Aminothiazoles / Imidolactams / Aryl chlorides show 12 more
- Substituents
- 1,3-thiazolamine / 2,4,5-trisubstituted 1,3-thiazole / Amine / Amino acid / Amino acid or derivatives / Aminopyridine / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle show 30 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 3H8GSZ4SQL
- CAS number
- 570406-98-3
- InChI Key
- OFZJKCQENFPZBH-UHFFFAOYSA-N
- InChI
- InChI=1S/C29H34Cl2N6O3S2/c30-20-15-23(41-17-20)24-27(37-12-10-35(11-13-37)21-4-2-1-3-5-21)42-29(33-24)34-26(38)19-14-22(31)25(32-16-19)36-8-6-18(7-9-36)28(39)40/h14-18,21H,1-13H2,(H,39,40)(H,33,34,38)
- IUPAC Name
- 1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)-1,3-thiazol-2-yl]carbamoyl}pyridin-2-yl)piperidine-4-carboxylic acid
- SMILES
- OC(=O)C1CCN(CC1)C1=C(Cl)C=C(C=N1)C(=O)NC1=NC(C2=CC(Cl)=CS2)=C(S1)N1CCN(CC1)C1CCCCC1
References
- General References
- Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, Allen LF, Hassanein T: Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology. 2018 May 17. pii: S0016-5085(18)34545-1. doi: 10.1053/j.gastro.2018.05.025. [Article]
- Qureshi K, Patel S, Meillier A: The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence. Int J Hepatol. 2016;2016:1802932. doi: 10.1155/2016/1802932. Epub 2016 Oct 9. [Article]
- Nomoto M, Pastino G, Rege B, Aluri J, Ferry J, Han D: Pharmacokinetics, Pharmacodynamics, Pharmacogenomics, Safety, and Tolerability of Avatrombopag in Healthy Japanese and White Subjects. Clin Pharmacol Drug Dev. 2018 Feb;7(2):188-195. doi: 10.1002/cpdd.349. Epub 2017 Mar 24. [Article]
- Yun SH, Sim EH, Goh RY, Park JI, Han JY: Platelet Activation: The Mechanisms and Potential Biomarkers. Biomed Res Int. 2016;2016:9060143. doi: 10.1155/2016/9060143. Epub 2016 Jun 15. [Article]
- Bussel JB, Kuter DJ, Aledort LM, Kessler CM, Cuker A, Pendergrass KB, Tang S, McIntosh J: A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014 Jun 19;123(25):3887-94. doi: 10.1182/blood-2013-07-514398. Epub 2014 May 6. [Article]
- Avotrombopag [Link]
- FDA Ok's avatrombopag [Link]
- Avatrombopag [Link]
- FDA approves avatrombopag for thrombocytopenia in adults with chronic liver disease [Link]
- Avatrombopag, a Novel Thrombopoietin Receptor Agonist, Increases Platelet Counts without Increasing Platelet Activation in Patients with Thrombocytopenia Due to Chronic Liver Disease [Link]
- Avotrombopag maleate approval, FDA [Link]
- NCI Drug Dictionary: Avotrombopag maleate [Link]
- Drugs.com: Avotrombopag [Link]
- NEJM Journal Watch: FDA Approval of Avatrombopag [Link]
- Avatrombopag Gains FDA Approval for Patients with Chronic Liver Disease [Link]
- FDA Approved Drug Products: Doptelet (avatrombopag) tablets for oral use (June 2021) [Link]
- Health Canada Product Monograph: Doptelet (avatrombopag maleate) tablets for oral use [Link]
- NICE UK review document, Avatrombopag [File]
- External Links
- Human Metabolome Database
- HMDB0248737
- PubChem Compound
- 9852519
- PubChem Substance
- 347828315
- ChemSpider
- 8028230
- 2045726
- ChEMBL
- CHEMBL2103883
- ZINC
- ZINC000072190218
- Wikipedia
- Avatrombopag
- FDA label
- Download (436 KB)
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 Immune Thrombocytopenia (ITP) 1 4 Not Yet Recruiting Prevention Cirrhosis of the Liver / Procedural haemorrhage / Thrombocytopenia; Drugs 1 4 Not Yet Recruiting Treatment Aplastic Anemia 1 4 Recruiting Prevention Chronic Hepatitis B Infection / Liver Failure, Acute on Chronic / Thrombocytopenia 1 4 Recruiting Treatment Chronic Liver Disease / Thrombocytopenia; Drugs 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 20 mg Tablet, film coated Oral 20 MG Tablet, film coated Oral 20 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8765764 No 2014-07-01 2023-01-15 US US7638536 No 2009-12-29 2025-05-05 US US8338429 No 2012-12-25 2023-06-30 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Insoluble https://medkoo.com/products/5199 - Predicted Properties
Property Value Source Water Solubility 0.00465 mg/mL ALOGPS logP 5.97 ALOGPS logP 4.17 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 3.5 Chemaxon pKa (Strongest Basic) 8.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 101.9 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 169.16 m3·mol-1 Chemaxon Polarizability 69.95 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 Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 236.28404 predictedDeepCCS 1.0 (2019) [M+H]+ 238.42021 predictedDeepCCS 1.0 (2019) [M+Na]+ 244.3328 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.
- Gene Name
- MPL
- Uniprot ID
- P40238
- Uniprot Name
- Thrombopoietin receptor
- Molecular Weight
- 71244.08 Da
References
- FDA Approved Drug Products: Doptelet (avatrombopag) tablets for oral use (June 2021) [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: Doptelet (avatrombopag) tablets for oral use (June 2021) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInducer
- Curator comments
- This enzyme action is based on in vitro data.
- 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
- Nomoto M, Ferry J, Hussein Z: Population Pharmacokinetic/Pharmacodynamic Analyses of Avatrombopag in Patients With Chronic Liver Disease and Optimal Dose Adjustment Guide With Concomitantly Administered CYP3A and CYP2C9 Inhibitors. J Clin Pharmacol. 2018 Jun 15. doi: 10.1002/jcph.1267. [Article]
- FDA Approved Drug Products: Doptelet (avatrombopag) tablets for oral use (June 2021) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- 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: Doptelet (avatrombopag) tablets for oral use (June 2021) [Link]
Transporters
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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: Doptelet (avatrombopag) tablets for oral use (June 2021) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- FDA Approved Drug Products: Doptelet (avatrombopag) tablets for oral use (June 2021) [Link]
Drug created at October 20, 2016 21:09 / Updated at February 14, 2024 00:55