U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C24H26FNO4
Molecular Weight 411.4659
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of FLUVASTATIN

SMILES

CC(C)N1C(\C=C\[C@H](O)C[C@H](O)CC(O)=O)=C(C2=C1C=CC=C2)C3=CC=C(F)C=C3

InChI

InChIKey=FJLGEFLZQAZZCD-JUFISIKESA-N
InChI=1S/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m0/s1

HIDE SMILES / InChI

Molecular Formula C24H26FNO4
Molecular Weight 411.4659
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 1
Optical Activity UNSPECIFIED

Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin is marketed under the trade names Lescol, Canef, Vastin. LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD Slow the progression of atherosclerosis in patients with CHD. Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.

Originator

Curator's Comment: # Novartis

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LESCOL

Approved Use

LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2)

Launch Date

1993
Primary
LESCOL

Approved Use

LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2)

Launch Date

1993
Primary
LESCOL

Approved Use

LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2)

Launch Date

1993
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
205 μg/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUVASTATIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
206.2 μg × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUVASTATIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.54 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUVASTATIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
640 mg 1 times / day multiple, oral
Highest studied dose
Dose: 640 mg, 1 times / day
Route: oral
Route: multiple
Dose: 640 mg, 1 times / day
Sources: Page: p.505
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: lipid metabolism disorder
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 7
Sources: Page: p.505
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Coadministration with rifampicin (CYP2C9 inducer) increased the CL/F of fluvastatin by 95% and to reduce AUC by 50%.
minor
minor
minor
minor
unknown (co-administration study)
Comment: Coadministration with cyclocporine resulted in 3.1-fold increase in AUC; however, cannot be explained through these mechanisms, since neither pravastatin nor fluvastatin has been shown to be a substrate for either P-gp or CYP3A4; coadministration with itraconazole had no significant impact on Cmax and AUC of fluvastatin
no
no
no
no
no
no
no
unknown (co-administration study)
Comment: Coadministration with cyclocporine resulted in 3.1-fold increase in AUC; however, cannot be explained through these mechanisms, since neither pravastatin nor fluvastatin has been shown to be a substrate for either P-gp or CYP3A4
Page: 14.0
yes
yes
yes
unlikely (co-administration study)
Comment: coadministered with rifampin. See https://pubmed.ncbi.nlm.nih.gov/29768081/. Pharmacogenomic study also performed. Not significant: see https://www.lipidjournal.com/article/S1933-2874(14)00072-5/pdf
yes
yes (pharmacogenomic study)
Comment: AUC of drug increased by 72%
PubMed

PubMed

TitleDatePubMed
Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.
1991 Oct
HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts.
1993 Nov 12
Fluvastatin in combination with other lipid-lowering agents.
1994 Dec
Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.
1994 Jun 6
Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination.
1994 May
Efficacy and safety of triple therapy (fluvastatin-bezafibrate-cholestyramine) for severe familial hypercholesterolemia.
1995 Jul 13
Fluvastatin in combination with other lipid-lowering agents.
1996 Jan
Troglitazone upregulates LDL receptor activity in HepG2 cells.
1998 Aug
Postural hypotension induced by paroxetine.
1998 Feb 21
[Cardiology in 1997].
1998 Oct 5
Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin.
2003 Jun
Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase activities.
2004 Jan
Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.
2004 Sep-Oct
Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.
2005
In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors.
2005 Apr
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro.
2005 Aug
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.
2005 Aug
[Fluvastatin-induced dermatomyositis].
2005 Dec
Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor.
2005 Jul
Immediate effects of fluvastain on circulating soluble endothelial protein C and free tissue factor pathway inhibitor in acute coronary syndromes.
2005 May
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes.
2005 Nov
Focal seizures after treatment with fluvastatin in a patient with a history of catastrophic antiphospholipid syndrome.
2005 Nov 15
Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells.
2005 Oct
Evaluation of the anti-HIV activity of statins.
2005 Oct 14
Binding thermodynamics of statins to HMG-CoA reductase.
2005 Sep 6
Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study.
2006 Dec
Muscle symptoms associated with statins: a series of twenty patients.
2006 Jan
Effect of low-density lipoprotein cholesterol on angiotensin II sensitivity: a randomized trial with fluvastatin.
2006 Jun
Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling.
2006 Mar
Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry.
2006 Mar 7
Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture.
2007 Jun
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma.
2007 Mar
Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat.
2008 May 31
Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors.
2009 Aug 1
Enantioselectivity in the pharmacokinetic interaction between fluvastatin and lercanidipine in healthy volunteers.
2009 Feb
Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice.
2009 Jan 15
Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes.
2009 Nov
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
2010 Dec
In vitro interactions between primycin and different statins in their effects against some clinically important fungi.
2010 Feb
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women.
2010 Mar
Effect of an antimicrobial agent on atherosclerotic plaques: assessment of metalloproteinase activity by molecular imaging.
2010 Mar 23
Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.
2010 Nov
The phototoxicity of fluvastatin, an HMG-CoA reductase inhibitor, is mediated by the formation of a benzocarbazole-like photoproduct.
2010 Nov
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.
2012 Dec
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter.
2013 Jul
ATP-dependent transport of statins by human and rat MRP2/Mrp2.
2013 Jun 1
Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.
2014 Aug
Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes.
2014 Sep
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.
2016 Jan-Feb
Patents

Sample Use Guides

Usual Adult Dose for Hyperlipidemia Immediate Release Capsules: -Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day -LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day -Maintenance dose: 20 mg to 80 mg per day Usual Adult Dose for Hyperlipoproteinemia Type IIa (Elevated LDL) Immediate Release Capsules: -Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day -LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day -Maintenance dose: 20 mg to 80 mg per day
Route of Administration: Oral
Fluvastatin markedly inhibits the formation of thiobarbituric acid reactive substances in iron (II)-supported peroxidation of liposomes with IC50 of 12 uM. Fluvastatin ranging from 1 uM to 100 uM inhibits peroxyl radical-mediated peroxidation of liposomes induced by water-soluble and lipid-soluble radical generators, 2,2'-azobis (2-amidinopropane) dihydro-chloride and 2,2'-azobis (2,4-dimethylvaleronitrile), respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:11:28 GMT 2023
Edited
by admin
on Fri Dec 15 16:11:28 GMT 2023
Record UNII
4L066368AS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUVASTATIN
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
FLUVASTATIN [VANDF]
Common Name English
FLUVASTATIN [MI]
Common Name English
NSC-758896
Code English
Fluvastatin [WHO-DD]
Common Name English
FLUVAS
Brand Name English
fluvastatin [INN]
Common Name English
6-HEPTENOIC ACID, 7-(3-(4-FLUOROPHENYL)-1-(1-METHYLETHYL)-1H-INDOL-2-YL)-3,5-DIHYDROXY-, (3R,5S,6E)-REL-
Systematic Name English
Classification Tree Code System Code
WHO-VATC QC10AA04
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
NDF-RT N0000175589
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
LIVERTOX NBK548435
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
NDF-RT N0000000121
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
NCI_THESAURUS C1655
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
WHO-ATC C10AA04
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
Code System Code Type Description
DAILYMED
4L066368AS
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
PUBCHEM
1548972
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
CHEBI
38561
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
NCI_THESAURUS
C61768
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
RXCUI
41127
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY RxNorm
ChEMBL
CHEMBL2220442
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
FDA UNII
4L066368AS
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
IUPHAR
2951
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
MESH
C065180
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
NSC
758896
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
INN
6547
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
HSDB
8366
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
EVMPD
SUB07768MIG
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
DRUG BANK
DB01095
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
EPA CompTox
DTXSID2020636
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
CAS
93957-54-1
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
LACTMED
Fluvastatin
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
SMS_ID
100000092352
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
MERCK INDEX
m5515
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
FLUVASTATIN
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
DRUG CENTRAL
1229
Created by admin on Fri Dec 15 16:11:28 GMT 2023 , Edited by admin on Fri Dec 15 16:11:28 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY