Identification

Name
Flumethasone
Accession Number
DB00663
Description

Flumethasone is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Thumb
Weight
Average: 410.458
Monoisotopic: 410.190480328
Chemical Formula
C22H28F2O5
Synonyms
  • 6alpha,9-Difluoro-11beta,17,21-trihydroxy-16alpha-methylpregna-1,4-diene-3,20-dione
  • Flumetasona
  • Flumétasone
  • Flumetasone
  • Flumetasonum
  • Flumethasone
External IDs
  • NSC-54702
  • RS 2177
  • U 10974
  • U-10,974
  • U-10974

Pharmacology

Indication

For the treatment of contact dermatitis, atopic dermatitis, exczema, psoriasis, diaper rash and other skin conditions

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Flumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.

Mechanism of action

Flumethasone is a glucocorticoid receptor agonist. This complex binds to the nucleus causing a variety of genetic activation and repressions. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flumethasone binds to plasma transcortin, and it becomes active when it is not bound to transcortin.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Humans
Absorption

Minimal if applied topically

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily hepatic

Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Can lead to signs of irritation such as burning sensation, itching or skin rash at the site of application; hypersensitivity reactions.

Affected organisms
  • Humans and other mammals
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.
DrugInteraction
AbametapirThe serum concentration of Flumethasone can be increased when it is combined with Abametapir.
AcarboseThe risk or severity of hyperglycemia can be increased when Flumethasone is combined with Acarbose.
AcetohexamideThe risk or severity of hyperglycemia can be increased when Flumethasone is combined with Acetohexamide.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Flumethasone is combined with Acetyldigitoxin.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Flumethasone.
AlbiglutideThe risk or severity of hyperglycemia can be increased when Flumethasone is combined with Albiglutide.
AlogliptinThe risk or severity of hyperglycemia can be increased when Flumethasone is combined with Alogliptin.
AminoglutethimideThe therapeutic efficacy of Flumethasone can be decreased when used in combination with Aminoglutethimide.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Flumethasone.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Flumethasone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Flumethasone acetateHB84ATQ00X2823-42-9ISSQQUKLQJHHOR-OSNGSNEUSA-N
Flumethasone pivalate0DV09X6F212002-29-1JWRMHDSINXPDHB-OJAGFMMFSA-N
International/Other Brands
Cerson (Riemser) / Locacorten (Novartis) / Locorten (Novartis) / Testohgen (Maeda Yakuhin)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Locacorten .03%CreamTopicalNovartis1966-12-311999-05-19Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Locacorten VioformFlumethasone pivalate (.02 %) + Clioquinol (3 %)OintmentTopicalNovartis1968-12-311998-05-08Canada
Locacorten VioformFlumethasone pivalate (0.02 %) + Clioquinol (3 %)CreamTopicalPaladin Labs Inc1968-12-31Not applicableCanada
Locacorten Vioform EardropsFlumethasone pivalate (0.02 %) + Clioquinol (1 %)Solution / dropsAuricular (otic)Paladin Labs Inc1969-12-31Not applicableCanada
LocasalenFlumethasone pivalate (.02 %) + Salicylic acid (3 %)OintmentTopicalNovartis1973-12-311999-10-31Canada
PMS-flumethasone-clioquinolFlumethasone pivalate (0.02 %) + Clioquinol (1.0 %)Solution / dropsAuricular (otic)Pharmascience IncNot applicableNot applicableCanada

Categories

ATC Codes
D07AB03 — FlumetasoneD07BB01 — Flumetasone and antisepticsS02CA02 — Flumetasone and antiinfectivesD07CB05 — Flumetasone and antibioticsD07XB01 — Flumetasone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Tertiary alcohols / Alpha-hydroxy ketones / Secondary alcohols
show 8 more
Substituents
11-beta-hydroxysteroid / 11-hydroxysteroid / 17-hydroxysteroid / 20-oxosteroid / 21-hydroxysteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 6-halo-steroid / 9-halo-steroid / Alcohol
show 24 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
11beta-hydroxy steroid, 17alpha-hydroxy steroid, glucocorticoid, 20-oxo steroid, fluorinated steroid, 3-oxo-Delta(1),Delta(4)-steroid, 21-hydroxy steroid (CHEBI:34764)

Chemical Identifiers

UNII
LR3CD8SX89
CAS number
2135-17-3
InChI Key
WXURHACBFYSXBI-GQKYHHCASA-N
InChI
InChI=1S/C22H28F2O5/c1-11-6-13-14-8-16(23)15-7-12(26)4-5-19(15,2)21(14,24)17(27)9-20(13,3)22(11,29)18(28)10-25/h4-5,7,11,13-14,16-17,25,27,29H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19+,20+,21+,22+/m1/s1
IUPAC Name
(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,13,15-trimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-5-one
SMILES
[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C

References

Synthesis Reference

Lincoln, F.H., Schneider, W.P. and Spero, G.B.; U.S. Patent 3,557,158; January 19, 1971; assigned to The Upjohn Co.

General References
Not Available
KEGG Drug
D04208
KEGG Compound
C14479
PubChem Compound
16490
PubChem Substance
46505121
ChemSpider
15632
BindingDB
50240002
RxNav
4458
ChEBI
34764
ChEMBL
CHEMBL1201392
ZINC
ZINC000003983936
Therapeutic Targets Database
DAP000814
PharmGKB
PA164749388
Wikipedia
Flumethasone
AHFS Codes
  • 84:06.00 — Anti-inflammatory Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Not Available
Dosage Forms
FormRouteStrength
CreamTopical0.2 mg/g
SolutionOral0.2 mg/g
CreamTopical
CreamTopical
Solution / dropsAuricular (otic)
OintmentTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)219 °C (base only)Not Available
water solubility0.392 mg/LNot Available
logP3.86HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0853 mg/mLALOGPS
logP1.91ALOGPS
logP1.34ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)12.42ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity102.32 m3·mol-1ChemAxon
Polarizability41.25 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9877
Blood Brain Barrier+0.9664
Caco-2 permeable+0.5146
P-glycoprotein substrateSubstrate0.8083
P-glycoprotein inhibitor IInhibitor0.5199
P-glycoprotein inhibitor IINon-inhibitor0.7781
Renal organic cation transporterNon-inhibitor0.8453
CYP450 2C9 substrateNon-substrate0.9008
CYP450 2D6 substrateNon-substrate0.908
CYP450 3A4 substrateSubstrate0.7477
CYP450 1A2 substrateNon-inhibitor0.9087
CYP450 2C9 inhibitorNon-inhibitor0.9052
CYP450 2D6 inhibitorNon-inhibitor0.9591
CYP450 2C19 inhibitorNon-inhibitor0.9337
CYP450 3A4 inhibitorNon-inhibitor0.7935
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9005
Ames testNon AMES toxic0.8008
CarcinogenicityNon-carcinogens0.9259
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4249 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9912
hERG inhibition (predictor II)Non-inhibitor0.6792
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - DI-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0079-2891000000-1cedbe5b5cccc84ebdb1

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Maier C, Runzler D, Schindelar J, Grabner G, Waldhausl W, Kohler G, Luger A: G-protein-coupled glucocorticoid receptors on the pituitary cell membrane. J Cell Sci. 2005 Aug 1;118(Pt 15):3353-61. [PubMed:16079279]
  4. Labeur M, Holsboer F: Molecular mechanisms of glucocorticoid receptor signaling. Medicina (B Aires). 2010;70(5):457-62. [PubMed:20920967]

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
  1. CRDD [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on August 14, 2020 04:24

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