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Details

Stereochemistry RACEMIC
Molecular Formula C24H25FNO4.Na
Molecular Weight 433.4478
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of FLUVASTATIN SODIUM

SMILES

[Na+].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=ZGGHKIMDNBDHJB-RPQBTBOMSA-M
InChI=1S/C24H26FNO4.Na/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);/q;+1/p-1/b12-11+;/t18-,19-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C24H25FNO4
Molecular Weight 410.458
Charge -1
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 1
Optical Activity UNSPECIFIED

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

7.5729601E11
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

7.5729601E11
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

7.5729601E11
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
Efficacy and safety of triple therapy (fluvastatin-bezafibrate-cholestyramine) for severe familial hypercholesterolemia.
1995 Jul 13
Currently available hypolipidaemic drugs and future therapeutic developments.
1995 Oct
Fluvastatin in combination with other lipid-lowering agents.
1996 Jan
Effect of fluvastatin or bezafibrate on the distribution of high density lipoprotein subpopulations in patients with familial hypercholesterolemia.
1996 Sep
Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on nitric oxide-induced hydroxyl radical generation in the rat heart.
2001 Apr 30
Structural mechanism for statin inhibition of HMG-CoA reductase.
2001 May 11
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.
2002 Jan 11
Valsartan therapy has additive anti-oxidative effect to that of fluvastatin therapy against low-density lipoprotein oxidation: studies in hypercholesterolemic and hypertensive patients.
2002 Jul
Statins and risk of polyneuropathy: a case-control study.
2002 May 14
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
Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.
2005
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro.
2005 Aug
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes.
2005 Nov
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
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
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma.
2007 Mar
Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors.
2009 Aug 1
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women.
2010 Mar
Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.
2014 Aug
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
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 Thu Jul 06 11:01:55 UTC 2023
Edited
by admin
on Thu Jul 06 11:01:55 UTC 2023
Record UNII
PYF7O1FV7F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUVASTATIN SODIUM
EP   JAN   MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
6-HEPTENOIC ACID, 7-(3-(4-FLUOROPHENYL)-1-(1-METHYLETHYL)-1H-INDOL-2-YL)-3,5-DIHYDROXY-, MONOSODIUM SALT, (R*,S*-(E))-(±)-
Common Name English
LIPAXAN
Brand Name English
FRACTAL
Brand Name English
FLUVASTATIN SODIUM SALT [MI]
Common Name English
CANEF
Brand Name English
LESCOL
Brand Name English
SODIUM (±)-(3R*,5S*,6E)-7-(3-(P-FLUOROPHENYL)-1-ISOPROPYLINDOL-2-YL)-3,5-DIHYDROXY-6-HEPTENOATE
Common Name English
FLUINDOSTATIN
Common Name English
VASTIN
Brand Name English
LOCOL
Brand Name English
XU 62-320
Code English
CRANOC
Brand Name English
XU-62-320
Code English
FLUVASTATIN SODIUM [ORANGE BOOK]
Common Name English
FLUVASTATIN SODIUM [MART.]
Common Name English
FLUVASTATIN SODIUM [USP MONOGRAPH]
Common Name English
LOCHOL
Brand Name English
FLUVASTATIN SODIUM [JAN]
Common Name English
FLUVASTATIN SODIUM [EP MONOGRAPH]
Common Name English
FLUVASTATIN SODIUM [USP IMPURITY]
Common Name English
FLUVASTATIN SODIUM [USP-RS]
Common Name English
PRIMEXIN
Brand Name English
FLUVASTATIN SODIUM SALT
MI  
Common Name English
FLUVASTATIN SODIUM [VANDF]
Common Name English
Fluvastatin sodium [WHO-DD]
Common Name English
FLUVASTATIN SODIUM [USAN]
Common Name English
ALMASTATIN
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1655
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
Code System Code Type Description
DAILYMED
PYF7O1FV7F
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
EVMPD
SUB02243MIG
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
EPA CompTox
DTXSID3044758
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
PUBCHEM
23679527
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
CHEBI
5137
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
RS_ITEM_NUM
1285931
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
NCI_THESAURUS
C29062
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
MERCK INDEX
M5515
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY Merck Index
RXCUI
72875
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY RxNorm
DRUG BANK
DBSALT000088
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
USAN
BB-10
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
FDA UNII
PYF7O1FV7F
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
CAS
93957-55-2
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
CHEBI
38561
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
ChEMBL
CHEMBL2220442
Created by admin on Thu Jul 06 11:01:55 UTC 2023 , Edited by admin on Thu Jul 06 11:01:55 UTC 2023
PRIMARY
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BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
PARENT -> SALT/SOLVATE
BASIS OF STRENGTH->SUBSTANCE
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ACTIVE MOIETY