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

Stem definitionDrug idCAS RN
antiestrogens or estrogen receptor modulators, clomifene and tamoxifen derivatives 2351 84449-90-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • raloxifene
  • keoxifene
  • raloxifene hydrochloride
  • evista
  • raloxifene HCl
A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.
  • Molecular weight: 473.59
  • Formula: C28H27NO4S
  • CLOGP: 6.86
  • LIPINSKI: 1
  • HAC: 5
  • HDO: 2
  • TPSA: 70
  • ALOGS: -5.97
  • ROTB: 7

  • 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) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.01 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.10 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 21.12 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 2 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 7.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 10.80 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.05 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 12.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 9, 1997 FDA LILLY

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
Breast cancer 604.71 29.52 161 2435 9334 2346155
Deep vein thrombosis 524.33 29.52 154 2442 12778 2342711
Pulmonary embolism 453.09 29.52 149 2447 17934 2337555
Endometrial cancer 437.41 29.52 77 2519 570 2354919
Bone density decreased 297.93 29.52 63 2533 1307 2354182
Spinal compression fracture 230.80 29.52 54 2542 1797 2353692
Fall 225.24 29.52 119 2477 46980 2308509
Fracture 214.83 29.52 55 2541 2676 2352813
Hip fracture 211.63 29.52 61 2535 4651 2350838
Breast cancer female 207.72 29.52 47 2549 1343 2354146
Cerebral infarction 197.27 29.52 57 2539 4380 2351109
Retinal vein thrombosis 186.09 29.52 31 2565 156 2355333
Cerebrovascular accident 162.48 29.52 73 2523 20113 2335376
Spinal fracture 160.65 29.52 44 2552 2775 2352714
Transient ischaemic attack 159.93 29.52 52 2544 5926 2349563
Retinal vein occlusion 147.56 29.52 30 2566 506 2354983
Muscle spasms 139.32 29.52 67 2529 21499 2333990
Body height decreased 132.71 29.52 32 2564 1209 2354280
Hot flush 123.77 29.52 45 2551 7154 2348335
Oedema peripheral 121.49 29.52 63 2533 23700 2331789
Thoracic vertebral fracture 121.10 29.52 26 2570 577 2354912
Breast cancer in situ 115.19 29.52 23 2573 352 2355137
Oestrogen receptor assay positive 111.04 29.52 19 2577 115 2355374
Compression fracture 110.56 29.52 26 2570 880 2354609
Thrombosis 109.82 29.52 44 2552 9100 2346389
Femur fracture 107.97 29.52 40 2556 6699 2348790
Visual acuity reduced 105.72 29.52 37 2559 5261 2350228
Pain in extremity 104.07 29.52 70 2526 42470 2313019
Pelvic fracture 99.78 29.52 26 2570 1349 2354140
Lumbar vertebral fracture 97.35 29.52 23 2573 794 2354695
Back pain 86.83 29.52 56 2540 31603 2323886
Injection site haemorrhage 75.82 29.52 31 2565 6736 2348753
Multiple fractures 75.74 29.52 18 2578 637 2354852
Postmenopausal haemorrhage 75.61 29.52 17 2579 469 2355020
Rib fracture 75.23 29.52 24 2572 2561 2352928
Dizziness 73.72 29.52 65 2531 58600 2296889
Uterine cancer 71.63 29.52 18 2578 806 2354683
Myocardial infarction 68.31 29.52 40 2556 18973 2336516
Ovarian cancer 67.86 29.52 19 2577 1294 2354195
Embolism 67.86 29.52 19 2577 1294 2354195
Endometrial cancer stage I 67.28 29.52 11 2585 48 2355441
Arthralgia 65.88 29.52 59 2537 54226 2301263
Retinal haemorrhage 65.01 29.52 18 2578 1176 2354313
Blindness unilateral 64.21 29.52 18 2578 1231 2354258
Embolism venous 58.92 29.52 13 2583 328 2355161
Retinal vascular thrombosis 57.81 29.52 10 2586 65 2355424
Osteonecrosis 57.13 29.52 26 2570 7316 2348173
Feeling abnormal 55.58 29.52 38 2558 23543 2331946
Endometrial cancer stage II 55.03 29.52 8 2588 12 2355477
Femoral neck fracture 54.59 29.52 16 2580 1283 2354206
Hypertension 52.74 29.52 39 2557 27322 2328167
Wrist fracture 50.13 29.52 16 2580 1707 2353782
Breast cancer stage III 50.00 29.52 10 2586 154 2355335
Gait disturbance 49.99 29.52 35 2561 22510 2332979
Atrial fibrillation 49.51 29.52 29 2567 13739 2341750
Osteoporosis 48.67 29.52 20 2576 4394 2351095
Asthenia 47.22 29.52 46 2550 46880 2308609
Bone pain 46.26 29.52 24 2572 8972 2346517
Cataract 46.20 29.52 21 2575 5887 2349602
Blindness 45.42 29.52 18 2578 3600 2351889
Blood cholesterol increased 45.36 29.52 20 2576 5221 2350268
Condition aggravated 45.26 29.52 38 2558 31941 2323548
Pain 45.03 29.52 51 2545 61806 2293683
Product complaint 44.78 29.52 19 2577 4519 2350970
Breast cancer recurrent 43.89 29.52 12 2584 747 2354742
Aspartate aminotransferase increased 43.85 29.52 26 2570 12586 2342903
Alanine aminotransferase increased 41.29 29.52 26 2570 14006 2341483
Vaginal haemorrhage 39.88 29.52 18 2578 4962 2350527
Blood alkaline phosphatase increased 38.12 29.52 19 2577 6526 2348963
No adverse event 36.71 29.52 21 2575 9507 2345982
Uterine polyp 36.34 29.52 9 2587 379 2355110
Vision blurred 35.38 29.52 24 2572 14644 2340845
Surgery 35.02 29.52 17 2579 5518 2349971
Endometrial hyperplasia 34.89 29.52 8 2588 241 2355248
Drug ineffective 34.59 29.52 58 2538 101566 2253923
Hepatic function abnormal 33.47 29.52 17 2579 6075 2349414
Colon cancer 33.22 29.52 12 2584 1861 2353628
Visual impairment 32.63 29.52 21 2575 11734 2343755
Blood pressure increased 32.21 29.52 24 2572 16962 2338527
Decreased appetite 32.20 29.52 30 2566 28861 2326628
Kyphosis 32.09 29.52 8 2588 346 2355143
Osteoporotic fracture 31.85 29.52 8 2588 357 2355132
Endometrial cancer stage III 30.73 29.52 5 2591 21 2355468
Arthritis 30.65 29.52 19 2577 9949 2345540
Discomfort 30.11 29.52 15 2581 5144 2350345
Loss of consciousness 30.08 29.52 24 2572 18743 2336746
Blood calcium increased 29.85 29.52 10 2586 1241 2354248

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

Pharmacologic Action:

SourceCodeDescription
ATC G03XC01 GENITO URINARY SYSTEM AND SEX HORMONES
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
Selective estrogen receptor modulators
FDA EPC N0000175826 Estrogen Agonist/Antagonist
MeSH PA D050071 Bone Density Conservation Agents
MeSH PA D004965 Estrogen Antagonists
MeSH PA D020847 Estrogen Receptor Modulators
MeSH PA D006727 Hormone Antagonists
MeSH PA D020845 Selective Estrogen Receptor Modulators
CHEBI has role CHEBI:50646 bone density conservation agent
CHEBI has role CHEBI:50739 estrogen receptor modulator
CHEBI has role CHEBI:50837 estrogen antagonist

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Postmenopausal osteoporosis indication 102447009
Prevention of Breast Carcinoma indication
Prevention of Glucocorticoid-Induced Osteoporosis off-label use
Lupus anticoagulant disorder contraindication 19267009
Hypertensive disorder contraindication 38341003 DOID:10763
Thrombosis of retinal vein contraindication 46085004
Chronic heart failure contraindication 48447003
Atrial fibrillation contraindication 49436004 DOID:0060224
Thrombophlebitis contraindication 64156001 DOID:3875
Deep venous thrombosis contraindication 128053003
Impaired renal function disorder contraindication 197663003
Cerebrovascular accident contraindication 230690007
Pulmonary thromboembolism contraindication 233935004
Thrombophilia contraindication 234467004 DOID:2452
Disease of liver contraindication 235856003 DOID:409
Transient ischemic attack contraindication 266257000 DOID:224
Pregnancy, function contraindication 289908002
Hypertriglyceridemia contraindication 302870006
Cardiovascular event risk contraindication 395112001
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Smokes tobacco daily contraindication 449868002

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.13 acidic
pKa2 8.6 acidic
pKa3 9.15 Basic

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
Estrogen receptor Nuclear hormone receptor ANTAGONIST IC50 9.40 WOMBAT-PK IUPHAR
Estrogen receptor beta Nuclear hormone receptor MODULATOR EC50 8 WOMBAT-PK CHEMBL
D(1A) dopamine receptor GPCR Ki 5.71 DRUG MATRIX
D(2) dopamine receptor GPCR Ki 6.41 DRUG MATRIX
Adenosine receptor A2a GPCR Ki 5.93 DRUG MATRIX
Alpha-2A adrenergic receptor GPCR Ki 6.20 DRUG MATRIX
Sodium-dependent serotonin transporter Transporter Ki 5.72 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 6.55 DRUG MATRIX
5-hydroxytryptamine receptor 2A GPCR Ki 6.38 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 6.21 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 5.77 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.27 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 6.97 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 5.83 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 6.32 DRUG MATRIX
Kappa-type opioid receptor GPCR Ki 6.19 DRUG MATRIX
Delta-type opioid receptor GPCR Ki 5.63 DRUG MATRIX
Acetylcholinesterase Enzyme IC50 6.40 DRUG MATRIX
Cytochrome P450 2C9 Enzyme IC50 5.70 DRUG MATRIX
Tyrosine-protein kinase Fyn Kinase IC50 5.44 DRUG MATRIX
Substance-K receptor GPCR Ki 5.88 DRUG MATRIX
Interleukin-6 Cytokine IC50 8.05 WOMBAT-PK
G-protein coupled estrogen receptor 1 GPCR EC50 6.50 WOMBAT-PK
5-hydroxytryptamine receptor 1D GPCR Ki 6.52 WOMBAT-PK
Aldehyde oxidase Enzyme IC50 8.54 WOMBAT-PK
5-hydroxytryptamine receptor 6 GPCR Ki 6.30 WOMBAT-PK
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase Enzyme Ki 9 WOMBAT-PK
Phospholipase D2 Enzyme IC50 5.47 CHEMBL
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor EC50 4.93 CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 7.42 CHEMBL
Phospholipase D1 Enzyme IC50 5.40 CHEMBL
5-hydroxytryptamine receptor 2B GPCR Ki 7.16 CHEMBL
Bile acid receptor Nuclear hormone receptor IC50 4.94 CHEMBL
Mu-type opioid receptor GPCR Ki 6.32 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 5.83 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 6.07 DRUG MATRIX
Membrane-associated progesterone receptor component 1 Membrane receptor Ki 6.63 DRUG MATRIX
Cruzipain Enzyme IC50 4.48 CHEMBL
Estrogen receptor Transcription factor IC50 8.73 CHEMBL
Estrogen receptor Transcription factor Ki 9.43 CHEMBL
C-8 sterol isomerase Enzyme Ki 7.18 CHEMBL
Estrogen receptor beta Transcription factor Ki 8.56 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 5.66 CHEMBL

External reference:

IDSource
4024098 VUID
N0000022103 NUI
C0244404 UMLSCUI
D02217 KEGG_DRUG
4F86W47BR6 UNII
82640-04-8 SECONDARY_CAS_RN
419530003 SNOMEDCT_US
4024098 VANDF
72143 RXNORM
109029006 SNOMEDCT_US
d04261 MMSL
83711 MMSL
007282 NDDF
CHEMBL81 ChEMBL_ID
CHEMBL1116 ChEMBL_ID
DB00481 DRUGBANK_ID
RAL PDB_CHEM_ID
CHEBI:8772 CHEBI
5388 INN_ID
D020849 MESH_DESCRIPTOR_UI
5035 PUBCHEM_CID
2820 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Evista HUMAN PRESCRIPTION DRUG LABEL 1 0002-4184 TABLET 60 mg ORAL NDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-7290 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0440-5295 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0904-6902 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 31722-256 TABLET 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-726 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43353-253 TABLET, FILM COATED 60 mg ORAL ANDA 20 sections
Raloxifene hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43598-505 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-3363 TABLET, FILM COATED 60 mg ORAL ANDA 20 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-3866 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50228-306 TABLET, FILM COATED 60 mg ORAL ANDA 20 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50268-694 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Evista HUMAN PRESCRIPTION DRUG LABEL 1 54868-4170 TABLET 60 mg ORAL NDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 60687-266 TABLET 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63629-7708 TABLET 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 63629-8209 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 65162-057 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 65862-709 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 66993-661 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 69097-825 TABLET 60 mg ORAL ANDA 19 sections
Raloxifene hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 71335-1460 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections
Raloxifene hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 71610-053 TABLET, FILM COATED 60 mg ORAL ANDA 20 sections
Raloxifene Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 76282-256 TABLET, FILM COATED 60 mg ORAL ANDA 19 sections