fluvastatin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antihyperlipidaemic substances, HMG CoA reductase inhibitors 1229 93957-54-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • lescol
  • fluvastatin
  • leschol
  • fluvastatin sodium
  • XU-62-320
  • fluvastatin sodium salt
  • fluvastatin sodium hydrate
An indole-heptanoic acid derivative that inhibits HMG COA REDUCTASE and is used to treat HYPERCHOLESTEROLEMIA. In contrast to other statins, it does not appear to interact with other drugs that inhibit CYP3A4.
  • Molecular weight: 411.47
  • Formula: C24H26FNO4
  • CLOGP: 4.05
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 3
  • TPSA: 82.69
  • ALOGS: -4.97
  • ROTB: 8

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
60 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.62 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 24 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.42 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 16 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.70 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 31, 1993 FDA NOVARTIS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myalgia 120.49 14.36 129 8322 122959 46554652
Blood creatine phosphokinase increased 109.29 14.36 66 8385 27658 46649953
Rhabdomyolysis 107.00 14.36 76 8375 41833 46635778
Limb reduction defect 100.08 14.36 21 8430 344 46677267
Dysmorphism 73.96 14.36 23 8428 1884 46675727
Cleft palate 71.25 14.36 19 8432 898 46676713
Talipes 63.21 14.36 19 8432 1388 46676223
Atrial septal defect 62.67 14.36 28 8423 6304 46671307
Gamma-glutamyltransferase increased 59.75 14.36 48 8403 31692 46645919
Limb hypoplasia congenital 58.75 14.36 12 8439 171 46677440
Patent ductus arteriosus 58.08 14.36 23 8428 3839 46673772
Antinuclear antibody negative 55.51 14.36 12 8439 228 46677383
Retrognathia 52.37 14.36 12 8439 300 46677311
Congenital oral malformation 51.98 14.36 11 8440 188 46677423
Herpes simplex reactivation 50.66 14.36 12 8439 348 46677263
Coombs positive haemolytic anaemia 49.71 14.36 12 8439 378 46677233
Aspartate aminotransferase increased 45.05 14.36 63 8388 78637 46598974
Alanine aminotransferase increased 43.64 14.36 66 8385 88385 46589226
Developmental hip dysplasia 43.63 14.36 14 8437 1269 46676342
Drug ineffective 40.59 14.36 38 8413 677800 45999811
Myopathy 39.83 14.36 23 8428 8858 46668753
Antiphospholipid syndrome 35.89 14.36 13 8438 1699 46675912
Gastritis haemorrhagic 35.19 14.36 12 8439 1314 46676297
Neck deformity 34.88 14.36 13 8438 1841 46675770
Lactic acidosis 30.39 14.36 34 8417 33875 46643736
Complex regional pain syndrome 30.00 14.36 12 8439 2054 46675557
Anxiety disorder 29.94 14.36 14 8437 3497 46674114
Pancreatitis acute 27.71 14.36 28 8423 24844 46652767
Premature baby 27.08 14.36 24 8427 18088 46659523
Aplasia 26.66 14.36 13 8438 3563 46674048
Muscular weakness 25.15 14.36 53 8398 91791 46585820
Muscle spasms 24.85 14.36 63 8388 123050 46554561
Blood alkaline phosphatase increased 23.07 14.36 32 8419 39577 46638034
Hyperlipidaemia 22.74 14.36 22 8429 18517 46659094
Neonatal seizure 22.00 14.36 6 8445 309 46677302
Pulmonary artery stenosis 21.11 14.36 5 8446 145 46677466
Rheumatoid arthritis 20.38 14.36 9 8442 240206 46437405
Hypernatraemia 19.60 14.36 13 8438 6388 46671223
Interstitial lung disease 19.48 14.36 35 8416 53914 46623697
Peripheral swelling 18.89 14.36 3 8448 158068 46519543
Chromaturia 18.76 14.36 18 8433 15001 46662610
Erysipelas 18.65 14.36 13 8438 6925 46670686
Blood creatinine increased 18.53 14.36 42 8409 76361 46601250
Product dose omission issue 18.42 14.36 4 8447 168516 46509095
Bradycardia neonatal 17.99 14.36 6 8445 614 46676997
Otospondylomegaepiphyseal dysplasia 17.90 14.36 4 8447 89 46677522
Pleuritic pain 17.19 14.36 12 8439 6404 46671207
Angiosclerosis 17.16 14.36 3 8448 17 46677594
Off label use 16.62 14.36 27 8424 379814 46297797
Hypothyroidism 16.31 14.36 24 8427 31314 46646297
Sterile pyuria 16.26 14.36 3 8448 24 46677587
Haematoma 16.00 14.36 24 8427 31848 46645763
Ocular myasthenia 15.64 14.36 4 8447 160 46677451
Acute kidney injury 15.64 14.36 84 8367 235771 46441840
Blood urea increased 15.54 14.36 21 8430 25331 46652280
Foetal exposure during pregnancy 15.22 14.36 23 8428 30724 46646887
Cerebral ischaemia 15.04 14.36 11 8440 6314 46671297
Coronary artery disease 14.97 14.36 24 8427 33728 46643883
Fasciitis 14.76 14.36 5 8446 536 46677075
Drug interaction 14.61 14.36 74 8377 203020 46474591
Cholestasis 14.58 14.36 21 8430 26872 46650739

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myalgia 243.75 15.48 178 7118 76489 29868693
Blood creatine phosphokinase increased 164.96 15.48 113 7183 43735 29901447
Myopathy 83.52 15.48 44 7252 10542 29934640
Muscle rupture 72.54 15.48 25 7271 2096 29943086
Gamma-glutamyltransferase increased 50.67 15.48 48 7248 29302 29915880
Rhabdomyolysis 45.34 15.48 66 7230 63514 29881668
Amyotrophic lateral sclerosis 38.76 15.48 13 7283 1003 29944179
Aspartate aminotransferase increased 32.98 15.48 57 7239 63365 29881817
Angina pectoris 30.87 15.48 37 7259 29481 29915701
Face oedema 30.69 15.48 24 7272 11310 29933872
Coronary artery disease 27.58 15.48 46 7250 49666 29895516
Off label use 26.33 15.48 14 7282 249276 29695906
Febrile bone marrow aplasia 26.03 15.48 19 7277 8078 29937104
Tendon rupture 26.00 15.48 18 7278 7046 29938136
Generalised oedema 25.54 15.48 22 7274 11863 29933319
Perioral dermatitis 20.95 15.48 5 7291 110 29945072
Congenital inguinal hernia 20.34 15.48 5 7291 125 29945057
Myocardial ischaemia 20.25 15.48 23 7273 17294 29927888
Toxicity to various agents 20.13 15.48 9 7287 177174 29768008
Alanine aminotransferase increased 18.99 15.48 50 7246 74226 29870956
General physical health deterioration 18.55 15.48 60 7236 99884 29845298
Death 17.71 15.48 38 7258 357245 29587937
Hyperkalaemia 17.45 15.48 45 7251 65965 29879217
Gross motor delay 17.10 15.48 5 7291 245 29944937
Dysuria 16.91 15.48 24 7272 22517 29922665
Palmoplantar keratoderma 16.32 15.48 5 7291 288 29944894
Blood creatinine increased 16.19 15.48 54 7242 91321 29853861
Glomerulonephritis chronic 16.12 15.48 4 7292 104 29945078
Polyneuropathy 16.08 15.48 17 7279 11806 29933376
Muscle spasms 15.91 15.48 43 7253 64795 29880387
Myoglobin blood increased 15.70 15.48 8 7288 1785 29943397
Angina unstable 15.51 15.48 17 7279 12293 29932889

Pharmacologic Action:

SourceCodeDescription
ATC C10AA04 CARDIOVASCULAR SYSTEM
LIPID MODIFYING AGENTS
LIPID MODIFYING AGENTS, PLAIN
HMG CoA reductase inhibitors
FDA MoA N0000000121 Hydroxymethylglutaryl-CoA Reductase Inhibitors
FDA EPC N0000175589 HMG-CoA Reductase Inhibitor
CHEBI has role CHEBI:35679 hypolipidemic agent
CHEBI has role CHEBI:77255 lethal toxin inhibitor
CHEBI has role CHEBI:35821 hypocholesteremic agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypercholesterolemia indication 13644009
Arteriosclerotic vascular disease indication 72092001
Familial hypercholesterolemia - heterozygous indication 238079002
Mixed hyperlipidemia indication 267434003
Slow Progression of Coronary Artery Disease indication
Cerebrovascular accident off-label use 230690007
Myocardial Infarction Prevention off-label use
Primary Prevention of Coronary Heart Disease off-label use
Prevention of Transient Ischemic Attacks off-label use
Alcoholism contraindication 7200002
Low blood pressure contraindication 45007003
Acute nephropathy contraindication 58574008
Disorder of muscle contraindication 129565002 DOID:423
Liver function tests abnormal contraindication 166603001
Hemorrhagic cerebral infarction contraindication 230706003
Disease of liver contraindication 235856003 DOID:409
Rhabdomyolysis contraindication 240131006
Pregnancy, function contraindication 289908002
Surgical procedure contraindication 387713003
Breastfeeding (mother) contraindication 413712001
Traumatic injury contraindication 417746004
Uncontrolled Epilepsy contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.05 acidic
pKa2 13.34 acidic
pKa3 13.99 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
3-hydroxy-3-methylglutaryl-coenzyme A reductase Enzyme INHIBITOR IC50 7.55 CHEMBL DRUG LABEL
Cytochrome P450 2C9 Enzyme IC50 6.40 DRUG MATRIX
Nuclear receptor subfamily 1 group I member 3 Nuclear hormone receptor WOMBAT-PK
3-hydroxy-3-methylglutaryl-coenzyme A reductase Enzyme IC50 8.60 CHEMBL

External reference:

IDSource
D00892 KEGG_DRUG
93957-55-2 SECONDARY_CAS_RN
4020854 VANDF
4023909 VANDF
C0082608 UMLSCUI
CHEBI:38561 CHEBI
115 PDB_CHEM_ID
CHEMBL1078 ChEMBL_ID
CHEMBL2220442 ChEMBL_ID
CHEMBL2218894 ChEMBL_ID
DB01095 DRUGBANK_ID
D000077340 MESH_DESCRIPTOR_UI
2951 IUPHAR_LIGAND_ID
6547 INN_ID
4L066368AS UNII
3403 PUBCHEM_CID
151972 RXNORM
1724 MMSL
189348 MMSL
4757 MMSL
d03183 MMSL
004439 NDDF
004440 NDDF
387585004 SNOMEDCT_US
412392009 SNOMEDCT_US
96307003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
LescolXL HUMAN PRESCRIPTION DRUG LABEL 1 0078-0354 TABLET, EXTENDED RELEASE 80 mg ORAL NDA 30 sections
Fluvastatin HUMAN PRESCRIPTION DRUG LABEL 1 0093-7442 CAPSULE 20 mg ORAL ANDA 26 sections
Fluvastatin HUMAN PRESCRIPTION DRUG LABEL 1 0093-7443 CAPSULE 40 mg ORAL ANDA 26 sections
Fluvastatin Sodium HUMAN PRESCRIPTION DRUG LABEL 1 0093-7446 TABLET, FILM COATED, EXTENDED RELEASE 80 mg ORAL ANDA 28 sections
Fluvastatin Sodium HUMAN PRESCRIPTION DRUG LABEL 1 0378-8020 CAPSULE 20 mg ORAL ANDA 26 sections
Fluvastatin Sodium HUMAN PRESCRIPTION DRUG LABEL 1 0378-8021 CAPSULE 40 mg ORAL ANDA 26 sections
Fluvastatin Sodium HUMAN PRESCRIPTION DRUG LABEL 1 0527-2580 TABLET, FILM COATED, EXTENDED RELEASE 80 mg ORAL ANDA 30 sections
FLUVASTATIN SODIUMER HUMAN PRESCRIPTION DRUG LABEL 1 0781-5370 TABLET, EXTENDED RELEASE 80 mg ORAL NDA authorized generic 26 sections
FLUVASTATIN SODIUMER HUMAN PRESCRIPTION DRUG LABEL 1 0781-8017 TABLET, EXTENDED RELEASE 80 mg ORAL NDA authorized generic 26 sections
LESCOL HUMAN PRESCRIPTION DRUG LABEL 1 54868-3329 CAPSULE 20 mg ORAL NDA 15 sections
LESCOL HUMAN PRESCRIPTION DRUG LABEL 1 54868-4224 CAPSULE 40 mg ORAL NDA 15 sections
LESCOL XL HUMAN PRESCRIPTION DRUG LABEL 1 54868-4601 TABLET, EXTENDED RELEASE 80 mg ORAL NDA 15 sections
Fluvastatin Sodium HUMAN PRESCRIPTION DRUG LABEL 1 68151-1326 CAPSULE 20 mg ORAL ANDA 25 sections
Fluvastatin Sodium HUMAN PRESCRIPTION DRUG LABEL 1 68151-1334 CAPSULE 40 mg ORAL ANDA 25 sections
Lescol XL HUMAN PRESCRIPTION DRUG LABEL 1 68151-4471 TABLET, EXTENDED RELEASE 80 mg ORAL NDA 26 sections