Identification
- Summary
Tafamidis is a medication used to treat transthyretin-mediated amyloidosis.
- Brand Names
- Vyndamax, Vyndaqel
- Generic Name
- Tafamidis
- DrugBank Accession Number
- DB11644
- Background
Tafamidis and tafamidis meglumine (FX-1006A) are benzoxazole derivatives1 developed by FoldRX.4 Tafamidis is structurally similar to diflusinal.4
Tafamidis was granted an EMA market authorisation on 16 November 20116 and FDA approval on 3 May 2019.7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Tafamidis (DB11644)
- Weight
- Average: 308.116
Monoisotopic: 306.980298509 - Chemical Formula
- C14H7Cl2NO3
- Synonyms
- Tafamidis
- Tafamidisum
- External IDs
- FX-006
- FX-1005
- FX-1006
- FX006
- FX1006
Pharmacology
- Indication
Tafamidis is indicated to treat cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults.2,3,7
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Tafamidis stabilizes transthyretin tetramers, reducing the amount of monomers available for amyloidogenesis.7 It has a long duration of action as it is given once daily, and a wide therapeutic window.7
- Mechanism of action
Genetic mutations or natural misfolding of transthyretin destabalizes transthyretin tetramers, leading to their dissociation and aggregation in tissues, and disrupting the normal function of these tissues.3,1 Tafamidis binds to transthyretin tetramers at the thyroxin binding sites, stabilizing the tetramer, reducing the availability of monomers for amyloidogenesis.1,6,7
Target Actions Organism ATransthyretin chaperoneHumans - Absorption
Tafamidis reaches a Cmax of 1430.93ng/mL with a Tmax of 1.75h fasted and 4h fed.1 The AUC of tafamidis is 47,864.31ng*h/mL.1
- Volume of distribution
The apparent volume of distribution at steady state is 18.5L.7
- Protein binding
Tafamidis 99.9% protein bound in plasma, mostly to transthyretin.7
- Metabolism
Tafamidis is largely not subject to first pass or oxidative metabolism, being 90% unchanged after in in vitro experiments.5 Preclinical data suggest tafamidis is mainly metabolized through glucuronidation and excreted in bile.7
- Route of elimination
A 20mg oral dose of tafamidis is approximately 59% recovered in the feces, largely as unchanged drug.7 Approximately 22% of a 20mg oral dose is recovered in the urine, mostly as the glucuronide metabolite.7
- Half-life
The half life of tafamidis is 49h.7
- Clearance
The oral clearance of tafamidis is 0.263L/h.7 The apparent total clearance is 0.44L/h.1
- Adverse Effects
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Data regarding overdoses of tafamidis are not readily available.7 In a clinical trial, some patients were given up to 6 times the normal dose with one reported case of mild hordeolum.7
- 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 softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Tafamidis. Acamprosate The excretion of Acamprosate can be decreased when combined with Tafamidis. Acyclovir The excretion of Acyclovir can be decreased when combined with Tafamidis. Adefovir dipivoxil The excretion of Adefovir dipivoxil can be decreased when combined with Tafamidis. Afatinib The serum concentration of Afatinib can be increased when it is combined with Tafamidis. Allopurinol The serum concentration of Allopurinol can be increased when it is combined with Tafamidis. Alpelisib The serum concentration of Alpelisib can be increased when it is combined with Tafamidis. Aminohippuric acid The excretion of Aminohippuric acid can be decreased when combined with Tafamidis. Apixaban The serum concentration of Apixaban can be increased when it is combined with Tafamidis. Avibactam The excretion of Avibactam can be decreased when combined with Tafamidis. 
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- Take with or without 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 Tafamidis meglumine ZU7CF08A1A 951395-08-7 DQJDBUPLRMRBAB-WZTVWXICSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Vyndamax Capsule, liquid filled 61 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2019-08-27 Not applicable US 
Vyndamax Capsule 61 mg Oral Pfizer Canada Ulc 2021-09-15 Not applicable Canada 
Vyndaqel Capsule 20 mg Oral Pfizer Canada Ulc 2020-04-07 Not applicable Canada Vyndaqel Capsule 20 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU 
Vyndaqel Capsule 20 mg/1 Oral Pfizer Labs Division of Pfizer Inc. 2015-12-15 Not applicable US Vyndaqel Capsule 61 mg Oral Pfizer Europe Ma Eeig 2020-12-23 Not applicable EU Vyndaqel Capsule 61 mg Oral Pfizer Europe Ma Eeig 2020-12-23 Not applicable EU Vyndaqel Capsule 20 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU Vyndaqel Capsule, liquid filled 20 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2019-05-16 Not applicable US
Categories
- ATC Codes
- N07XX08 — Tafamidis
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenyl-1,3-oxazoles. These are aromatic heterocyclic compounds containing a 1,3-oxazole substituted at one or more positions by a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azoles
- Sub Class
- Oxazoles
- Direct Parent
- Phenyl-1,3-oxazoles
- Alternative Parents
- Benzoxazoles / Dichlorobenzenes / Aryl chlorides / Heteroaromatic compounds / Oxacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds show 4 more
- Substituents
- 1,3-dichlorobenzene / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzoxazole / Carboxylic acid / Carboxylic acid derivative / Chlorobenzene show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- 1,3-benzoxazoles, monocarboxylic acid, dichlorobenzene (CHEBI:78538)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8FG9H9D31J
- CAS number
- 594839-88-0
- InChI Key
- TXEIIPDJKFWEEC-UHFFFAOYSA-N
- InChI
- InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)
- IUPAC Name
- 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid
- SMILES
- OC(=O)C1=CC=C2N=C(OC2=C1)C1=CC(Cl)=CC(Cl)=C1
References
- General References
- Coelho T, Merlini G, Bulawa CE, Fleming JA, Judge DP, Kelly JW, Maurer MS, Plante-Bordeneuve V, Labaudiniere R, Mundayat R, Riley S, Lombardo I, Huertas P: Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis. Neurol Ther. 2016 Jun;5(1):1-25. doi: 10.1007/s40120-016-0040-x. Epub 2016 Feb 19. [Article]
- Gurwitz JH, Maurer MS: Tafamidis-A Pricey Therapy for a Not-So-Rare Condition. JAMA Cardiol. 2020 Jan 8. pii: 2758314. doi: 10.1001/jamacardio.2019.5233. [Article]
- Endo J, Sano M, Izumiya Y, Tsujita K, Nakamura K, Tahara N, Kuwahara K, Inomata T, Ueda M, Sekijima Y, Ando Y, Tsutsui H, Isobe M, Fukuda K: A Statement on the Appropriate Administration of Tafamidis in Patients With Transthyretin Cardiac Amyloidosis. Circ J. 2019 Dec 25;84(1):15-17. doi: 10.1253/circj.CJ-19-0811. Epub 2019 Nov 16. [Article]
- Ratner M: Spotlight focuses on protein-misfolding therapies. Nat Biotechnol. 2009 Oct;27(10):874. doi: 10.1038/nbt1009-874c. [Article]
- Lee KR, Jeong JW, Hyun HC, Jang E, Ahn S, Choi S, Joo SH, Kim S, Koo TS: Pharmacokinetics of tafamidis, a transthyretin amyloidosis drug, in rats. Xenobiotica. 2018 Aug;48(8):831-838. doi: 10.1080/00498254.2017.1366575. Epub 2017 Nov 16. [Article]
- Tafamadis SmPC EMA [Link]
- FDA Approved Drug Products: Vyndaqel Tafamidis Meglumine Oral Capsules [Link]
- External Links
- PDB Entries
- 3tct / 4his / 6e6z / 6e72 / 6e74 / 6e77 / 6fft
- FDA label
- Download (752 KB)
- MSDS
- Download (24.8 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Transthyretin Amyloid Cardiomyopathy 1 4 Completed Treatment Osteoarthritis of the Knee 1 4 Completed Treatment Transthyretin Amyloid Polyneuropathy (ATTR-PN) 1 4 Not Yet Recruiting Treatment Transthyretin Cardiac Amyloidosis 1 4 Recruiting Treatment Transthyretin Amyloidosis 1 3 Active Not Recruiting Treatment Transthyretin (TTR) Amyloid Cardiomyopathy 1 3 Completed Treatment ATTR-CM / TTR-CM 1 3 Completed Treatment ATTR-PN 1 3 Completed Treatment Osteoarthritis of the Knee 3 3 Completed Treatment Transthyretin (TTR) Amyloid Cardiomyopathy 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 61 mg Capsule, liquid filled Oral 61 mg/1 Capsule, liquid filled Oral 61 mg Capsule Oral 61.0 mg Capsule Oral 20 mg Capsule Oral 20 mg/1 Capsule, liquid filled Oral 20 mg/1 Capsule, liquid filled Oral 20 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7214696 No 2007-05-08 2023-12-19 US US9770441 No 2017-09-26 2035-08-31 US US8653119 No 2014-02-18 2024-01-28 US US7214695 No 2007-05-08 2024-04-27 US US8168663 No 2012-05-01 2023-12-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility >50mg/mL ChemSpider - Predicted Properties
Property Value Source Water Solubility 0.0323 mg/mL ALOGPS logP 3.91 ALOGPS logP 4.21 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 3.6 Chemaxon pKa (Strongest Basic) -0.4 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 63.33 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 84.69 m3·mol-1 Chemaxon Polarizability 29.74 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Chaperone
- General Function
- Identical protein binding
- Specific Function
- Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
- Gene Name
- TTR
- Uniprot ID
- P02766
- Uniprot Name
- Transthyretin
- Molecular Weight
- 15886.88 Da
References
- Endo J, Sano M, Izumiya Y, Tsujita K, Nakamura K, Tahara N, Kuwahara K, Inomata T, Ueda M, Sekijima Y, Ando Y, Tsutsui H, Isobe M, Fukuda K: A Statement on the Appropriate Administration of Tafamidis in Patients With Transthyretin Cardiac Amyloidosis. Circ J. 2019 Dec 25;84(1):15-17. doi: 10.1253/circj.CJ-19-0811. Epub 2019 Nov 16. [Article]
- FDA Approved Drug Products: Vyndaqel Tafamidis Meglumine Oral Capsules [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Tafamadis SmPC EMA [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Tafamadis SmPC EMA [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Tafamadis SmPC EMA [Link]
Drug created at October 17, 2016 21:30 / Updated at March 22, 2023 23:54