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 134.52 15.11 135 8515 133356 53207060
Blood creatine phosphokinase increased 113.30 15.11 66 8584 28919 53311497
Rhabdomyolysis 111.33 15.11 76 8574 43847 53296569
Limb reduction defect 101.27 15.11 21 8629 364 53340052
Dysmorphism 72.70 15.11 23 8627 2227 53338189
Cleft palate 71.06 15.11 19 8631 1015 53339401
Talipes 64.05 15.11 19 8631 1483 53338933
Atrial septal defect 63.27 15.11 28 8622 6886 53333530
Gamma-glutamyltransferase increased 62.06 15.11 48 8602 33507 53306909
Patent ductus arteriosus 59.10 15.11 23 8627 4095 53336321
Limb hypoplasia congenital 59.00 15.11 12 8638 188 53340228
Antinuclear antibody negative 56.82 15.11 12 8638 228 53340188
Congenital oral malformation 53.19 15.11 11 8639 188 53340228
Herpes simplex reactivation 51.27 15.11 12 8638 370 53340046
Coombs positive haemolytic anaemia 51.02 15.11 12 8638 378 53340038
Retrognathia 49.77 15.11 12 8638 421 53339995
Aspartate aminotransferase increased 47.24 15.11 63 8587 83966 53256450
Alanine aminotransferase increased 45.54 15.11 66 8584 95029 53245387
Developmental hip dysplasia 44.65 15.11 14 8636 1316 53339100
Drug ineffective 41.58 15.11 43 8607 817202 52523214
Myopathy 40.32 15.11 23 8627 9669 53330747
Antiphospholipid syndrome 36.90 15.11 13 8637 1753 53338663
Gastritis haemorrhagic 35.16 15.11 12 8638 1472 53338944
Neck deformity 35.07 15.11 13 8637 2026 53338390
Lactic acidosis 30.84 15.11 34 8616 37219 53303197
Complex regional pain syndrome 30.43 15.11 12 8638 2211 53338205
Anxiety disorder 29.70 15.11 14 8636 3976 53336440
Jaundice 29.22 15.11 30 8620 30283 53310133
Pancreatitis acute 29.16 15.11 28 8622 26081 53314335
Premature baby 27.51 15.11 24 8626 19777 53320639
Rheumatoid arthritis 26.49 15.11 9 8641 314522 53025894
Aplasia 26.05 15.11 13 8637 4179 53336237
Acute kidney injury 25.79 15.11 95 8555 253773 53086643
Muscular weakness 25.70 15.11 53 8597 100939 53239477
Muscle spasms 25.65 15.11 63 8587 134732 53205684
Blood alkaline phosphatase increased 24.75 15.11 32 8618 41330 53299086
Interstitial lung disease 24.21 15.11 38 8612 58584 53281832
Hyperlipidaemia 23.85 15.11 22 8628 19493 53320923
Neonatal seizure 21.34 15.11 6 8644 387 53340029
Peripheral swelling 20.98 15.11 4 8646 206104 53134312
Off label use 20.54 15.11 28 8622 472184 52868232
Pulmonary artery stenosis 20.28 15.11 5 8645 193 53340223
Hypernatraemia 19.85 15.11 13 8637 6984 53333432
Chromaturia 19.52 15.11 18 8632 15932 53324484
Blood creatinine increased 19.42 15.11 42 8608 82620 53257796
Erysipelas 19.34 15.11 13 8637 7288 53333128
Coronary artery disease 18.66 15.11 25 8625 33412 53307004
Otospondylomegaepiphyseal dysplasia 18.34 15.11 4 8646 89 53340327
Alopecia 17.62 15.11 8 8642 234575 53105841
Pleuritic pain 17.60 15.11 12 8638 6884 53333532
Angiosclerosis 16.95 15.11 3 8647 21 53340395
Haematoma 16.92 15.11 24 8626 33820 53306596
Blood urea increased 16.80 15.11 21 8629 26210 53314206
Cerebrovascular accident 16.75 15.11 46 8604 105128 53235288
Drug interaction 16.62 15.11 75 8575 219254 53121162
Sterile pyuria 16.59 15.11 3 8647 24 53340392
Bradycardia neonatal 16.42 15.11 6 8644 898 53339518
Joint swelling 16.12 15.11 9 8641 234629 53105787
Ocular myasthenia 16.03 15.11 4 8646 162 53340254
Hypothyroidism 15.73 15.11 24 8626 36083 53304333
Cerebral ischaemia 15.61 15.11 11 8639 6654 53333762
Fasciitis 15.32 15.11 5 8645 534 53339882
Cholestasis 15.32 15.11 21 8629 28674 53311742
Amyotrophic lateral sclerosis 15.14 15.11 6 8644 1120 53339296

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 248.24 15.55 182 7505 81048 32424791
Blood creatine phosphokinase increased 169.00 15.55 115 7572 45361 32460478
Myopathy 81.90 15.55 44 7643 11297 32494542
Muscle rupture 75.79 15.55 26 7661 2216 32503623
Gamma-glutamyltransferase increased 49.93 15.55 48 7639 30734 32475105
Rhabdomyolysis 45.43 15.55 67 7620 67198 32438641
Amyotrophic lateral sclerosis 42.46 15.55 14 7673 1056 32504783
Off label use 34.02 15.55 15 7672 306305 32199534
Vestibular neuronitis 33.89 15.55 8 7679 173 32505666
Aspartate aminotransferase increased 32.29 15.55 57 7630 66372 32439467
Dysuria 31.44 15.55 34 7653 24976 32480863
Face oedema 30.51 15.55 24 7663 11751 32494088
Angina pectoris 29.89 15.55 37 7650 31389 32474450
General physical health deterioration 29.36 15.55 76 7611 115183 32390656
Coronary artery disease 28.60 15.55 46 7641 49660 32456179
Tendon rupture 28.31 15.55 19 7668 7284 32498555
Myocardial infarction 27.15 15.55 78 7609 125598 32380241
Febrile bone marrow aplasia 25.88 15.55 19 7668 8396 32497443
Generalised oedema 25.17 15.55 22 7665 12461 32493378
Perioral dermatitis 21.06 15.55 5 7682 111 32505728
Myocardial ischaemia 20.34 15.55 23 7664 17736 32488103
Congenital inguinal hernia 20.27 15.55 5 7682 131 32505708
Death 19.67 15.55 38 7649 382479 32123360
Toxicity to various agents 19.28 15.55 9 7678 178032 32327807
Alanine aminotransferase increased 18.19 15.55 50 7637 78429 32427410
Funguria 18.08 15.55 4 7683 64 32505775
Gross motor delay 16.78 15.55 5 7682 270 32505569
Hyperkalaemia 16.72 15.55 45 7642 69705 32436134
Blood creatinine increased 16.40 15.55 55 7632 96077 32409762
Glomerulonephritis chronic 16.36 15.55 4 7683 101 32505738
Angina unstable 15.88 15.55 17 7670 12338 32493501
Palmoplantar keratoderma 15.78 15.55 5 7682 332 32505507
Myoglobin blood increased 15.62 15.55 8 7679 1859 32503980
Cholestatic liver injury 15.61 15.55 8 7679 1862 32503977
Myoglobin urine 15.58 15.55 3 7684 23 32505816

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
Nuclear receptor subfamily 1 group I member 3 Nuclear hormone receptor WOMBAT-PK
Cytochrome P450 2C9 Enzyme IC50 6.40 DRUG MATRIX
Retinoic acid receptor RXR-alpha Nuclear hormone receptor Kd 4.96 CHEMBL
Sodium/bile acid cotransporter Transporter IC50 4.40 CHEMBL
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
CHEMBL2220442 ChEMBL_ID
CHEMBL1078 ChEMBL_ID
CHEMBL2218894 ChEMBL_ID
D000077340 MESH_DESCRIPTOR_UI
DB01095 DRUGBANK_ID
23663976 PUBCHEM_CID
2951 IUPHAR_LIGAND_ID
6547 INN_ID
4L066368AS UNII
151972 RXNORM
1724 MMSL
189348 MMSL
4757 MMSL
d03183 MMSL
004439 NDDF
004440 NDDF
387585004 SNOMEDCT_US
412392009 SNOMEDCT_US
96307003 SNOMEDCT_US
CHEMBL103585 ChEMBL_ID

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 0781-8017 TABLET, EXTENDED RELEASE 80 mg ORAL NDA authorized generic 27 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 HUMAN PRESCRIPTION DRUG LABEL 1 63629-8737 CAPSULE 40 mg ORAL ANDA 26 sections
Fluvastatin HUMAN PRESCRIPTION DRUG LABEL 1 63629-8812 CAPSULE 20 mg ORAL ANDA 26 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