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

Stem definitionDrug idCAS RN
angiotensin II receptor antagonists, antihypertensive (non-peptidic) 1610 114798-26-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • losartan
  • allisartan
  • lortaan
  • losartan potassium
  • losartan monopotassium
  • losartan monopotassium salt
An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
  • Molecular weight: 422.92
  • Formula: C22H23ClN6O
  • CLOGP: 3.85
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 92.51
  • ALOGS: -4.97
  • ROTB: 8

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
50 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.05 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 12 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 3.95 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 35 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.37 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.20 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) 1.80 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
April 14, 1995 FDA MERCK SHARP DOHME

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
Hyperkalaemia 268.78 31.61 68 1370 5825 2350822
Acute kidney injury 257.53 31.61 94 1344 28028 2328619
Product substitution issue 243.51 31.61 61 1377 5008 2351639
Blood pressure increased 241.59 31.61 79 1359 16907 2339740
Dizziness 224.61 31.61 105 1333 58560 2298087
Hyponatraemia 193.33 31.61 63 1375 13262 2343385
Hypotension 148.44 31.61 66 1372 32370 2324277
Confusional state 112.64 31.61 50 1388 24294 2332353
Cough 97.97 31.61 50 1388 33067 2323580
Anuria 97.62 31.61 24 1414 1800 2354847
Syncope 95.50 31.61 40 1398 16835 2339812
Hypertension 94.76 31.61 46 1392 27315 2329332
Fall 94.59 31.61 55 1383 47044 2309603
Headache 90.24 31.61 65 1373 80114 2276533
Dyspnoea 84.40 31.61 62 1376 78671 2277976
Completed suicide 83.90 31.61 39 1399 20995 2335652
Blood pressure inadequately controlled 80.68 31.61 18 1420 882 2355765
Malaise 69.14 31.61 48 1390 55537 2301110
Renal impairment 67.51 31.61 27 1411 10065 2346582
Drug interaction 66.29 31.61 37 1401 29126 2327521
Toxicity to various agents 64.92 31.61 38 1400 32716 2323931
Drug ineffective 64.45 31.61 59 1379 101565 2255082
Orthostatic hypotension 64.26 31.61 19 1419 2860 2353787
Hypertensive crisis 62.33 31.61 18 1420 2495 2354152
Drug hypersensitivity 62.02 31.61 42 1396 46601 2310046
Dehydration 60.99 31.61 32 1406 22263 2334384
Acidosis 60.58 31.61 16 1422 1594 2355053
Pruritus 59.94 31.61 40 1398 43300 2313347
Metabolic acidosis 57.96 31.61 21 1417 5977 2350670
Angioedema 54.53 31.61 22 1416 8374 2348273
Vomiting 54.12 31.61 46 1392 71556 2285091
Hypoxia 53.51 31.61 20 1418 6207 2350440
Nausea 50.35 31.61 54 1384 112135 2244512
Purpura senile 49.79 31.61 7 1431 18 2356629
Thrombocytosis 48.57 31.61 12 1426 915 2355732
Suspiciousness 47.14 31.61 8 1430 89 2356558
Pulmonary oedema 46.79 31.61 19 1419 7344 2349303
Swollen tongue 45.31 31.61 17 1421 5326 2351321
Loss of consciousness 43.08 31.61 24 1414 18743 2337904
Cutaneous lupus erythematosus 42.70 31.61 10 1428 607 2356040
Adverse event 42.70 31.61 18 1420 7641 2349006
Renal failure 42.05 31.61 23 1415 17326 2339321
Inappropriate antidiuretic hormone secretion 41.90 31.61 13 1425 2296 2354351
Lactic acidosis 41.74 31.61 16 1422 5314 2351333
Arthralgia 41.19 31.61 35 1403 54250 2302397
Overdose 39.10 31.61 23 1415 19884 2336763
Tarsal tunnel syndrome 38.50 31.61 6 1432 37 2356610
Oligohydramnios 38.31 31.61 10 1428 950 2355697
Intestinal angioedema 37.95 31.61 7 1431 129 2356518
Constipation 37.34 31.61 23 1415 21606 2335041
Asthenia 37.11 31.61 31 1407 46895 2309752
Fatigue 36.46 31.61 40 1398 84833 2271814
Heart rate increased 36.30 31.61 18 1420 11087 2345560
Hyperglycaemia 35.88 31.61 14 1424 4871 2351776
Condition aggravated 35.87 31.61 26 1412 31953 2324694
Presyncope 35.54 31.61 13 1425 3790 2352857
Feeling abnormal 35.51 31.61 23 1415 23558 2333089
Oedema peripheral 35.35 31.61 23 1415 23740 2332907
Atrial septal defect 34.98 31.61 10 1428 1334 2355313
Vestibular disorder 34.28 31.61 7 1431 223 2356424
Blood pressure decreased 33.26 31.61 16 1422 9220 2347427
Arteritis 32.55 31.61 6 1432 110 2356537
Palpitations 32.27 31.61 19 1419 16437 2340210
Bradycardia 32.09 31.61 16 1422 9965 2346682
Irritable bowel syndrome 31.87 31.61 10 1428 1831 2354816

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
Angioedema 260.82 33.86 80 1186 9584 1735931
Hyperkalaemia 206.10 33.86 65 1201 8482 1737033
Acute kidney injury 157.91 33.86 79 1187 34865 1710650
Completed suicide 137.26 33.86 57 1209 16255 1729260
Hypotension 136.57 33.86 68 1198 29586 1715929
Cough 85.01 33.86 43 1223 19154 1726361
Product substitution issue 83.05 33.86 26 1240 3260 1742255
Hypertension 78.68 33.86 41 1225 19407 1726108
Blood pressure increased 75.04 33.86 33 1233 10720 1734795
Acidosis 74.19 33.86 20 1246 1477 1744038
Toxicity to various agents 70.77 33.86 44 1222 29097 1716418
Dyspnoea 66.52 33.86 53 1213 52006 1693509
Dizziness 64.14 33.86 44 1222 34317 1711198
Drug interaction 62.30 33.86 40 1226 27918 1717597
Hyponatraemia 54.38 33.86 25 1241 8975 1736540
Loss of consciousness 50.62 33.86 28 1238 14847 1730668
Orthostatic hypotension 50.19 33.86 18 1248 3413 1742102
Syncope 49.11 33.86 27 1239 14142 1731373
Fall 48.69 33.86 34 1232 27180 1718335
Myalgia 46.59 33.86 27 1239 15631 1729884
Fatigue 43.05 33.86 41 1225 50740 1694775
Carcinogenicity 42.57 33.86 6 1260 9 1745506
Nightmare 42.18 33.86 15 1251 2772 1742743
Malaise 41.69 33.86 32 1234 29533 1715982
Photosensitivity reaction 40.65 33.86 13 1253 1737 1743778
Visual impairment 39.82 33.86 18 1248 6200 1739315
Peripheral coldness 36.87 33.86 11 1255 1167 1744348
Eye infection 36.38 33.86 9 1257 471 1745044

Pharmacologic Action:

SourceCodeDescription
ATC C09CA01 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), PLAIN
Angiotensin II receptor blockers (ARBs), plain
ATC C09DA01 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
Angiotensin II receptor blockers (ARBs) and diuretics
ATC C09DB06 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
Angiotensin II receptor blockers (ARBs) and calcium channel blockers
MeSH PA D047228 Angiotensin II Type 1 Receptor Blockers
MeSH PA D057911 Angiotensin Receptor Antagonists
MeSH PA D000889 Anti-Arrhythmia Agents
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
FDA MoA N0000000070 Angiotensin 2 Receptor Antagonists
FDA EPC N0000175561 Angiotensin 2 Receptor Blocker

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Diabetic renal disease indication 127013003
Hypertensive urgency indication 443482000
Hypertension with Left Ventricular Hypertrophy indication
Chronic heart failure off-label use 48447003
Atrial fibrillation off-label use 49436004 DOID:0060224
Diastolic heart failure off-label use 418304008 DOID:9775
Nondiabetic Proteinuric Nephropathy off-label use
Anuria contraindication 2472002 DOID:2983
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Secondary angle-closure glaucoma contraindication 21571006
Hypovolemia contraindication 28560003
Dehydration contraindication 34095006
Hyperuricemia contraindication 35885006 DOID:1920
Hypokalemia contraindication 43339004
Low blood pressure contraindication 45007003
Systemic lupus erythematosus contraindication 55464009 DOID:9074
Sympathectomy contraindication 57071006
Hypercalcemia contraindication 66931009 DOID:12678
Hyperparathyroidism contraindication 66999008 DOID:13543
Hypochloremic alkalosis contraindication 70134007
Hepatic coma contraindication 72836002 DOID:12550
Diabetes mellitus contraindication 73211009 DOID:9351
Hyponatremia contraindication 89627008
Gout contraindication 90560007 DOID:13189
Hypomagnesemia contraindication 190855004
Acute pancreatitis contraindication 197456007 DOID:2913
Impaired renal function disorder contraindication 197663003
Disease of liver contraindication 235856003 DOID:409
Neonatal hyperbilirubinemia contraindication 281610001
Pregnancy, function contraindication 289908002
Renal artery stenosis contraindication 302233006
Azotemia contraindication 445009001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.5 acidic
pKa2 13.19 acidic
pKa3 3.89 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
Type-1 angiotensin II receptor GPCR ANTAGONIST IC50 9.48 CHEMBL CHEMBL
Phosphodiesterase 4 Enzyme IC50 4.59 CHEMBL
Angiotensin-converting enzyme Enzyme IC50 7.72 CHEMBL
Type-2 angiotensin II receptor GPCR IC50 5 CHEMBL
Angiotensin II receptor GPCR Kd 8.43 CHEMBL
Phosphodiesterase 3 Enzyme IC50 4.89 CHEMBL
Cytochrome P450 2C9 Enzyme IC50 5.54 DRUG MATRIX
Multidrug resistance protein 1 Transporter Km 3.50 WOMBAT-PK
Type-1 angiotensin II receptor GPCR Kd 8.80 CHEMBL
Angiotensin II receptor GPCR IC50 8.34 CHEMBL
Type-1B angiotensin II receptor GPCR Ki 8.44 CHEMBL
Type-2 angiotensin II receptor GPCR IC50 5.13 CHEMBL
Type-1A angiotensin II receptor GPCR Ki 7.84 CHEMBL
Type-1 angiotensin II receptor GPCR IC50 7.02 CHEMBL
Angiotensin II receptor (AT-1) type-1 GPCR Ki 8.72 CHEMBL
Type-1 angiotensin II receptor GPCR IC50 7.74 CHEMBL

External reference:

IDSource
4020913 VUID
N0000148401 NUI
C0126174 UMLSCUI
D00357 KEGG_DRUG
3ST302B24A UNII
124750-99-8 SECONDARY_CAS_RN
96309000 SNOMEDCT_US
4020913 VANDF
52175 RXNORM
373567002 SNOMEDCT_US
d03821 MMSL
004991 NDDF
CHEMBL995 ChEMBL_ID
CHEMBL191 ChEMBL_ID
DB00678 DRUGBANK_ID
6913 INN_ID
LSN PDB_CHEM_ID
CHEBI:149504 CHEBI
D019808 MESH_DESCRIPTOR_UI
3961 PUBCHEM_CID
590 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
HYZAAR HUMAN PRESCRIPTION DRUG LABEL 2 0006-0717 TABLET, FILM COATED 50 mg ORAL NDA 19 sections
HYZAAR HUMAN PRESCRIPTION DRUG LABEL 2 0006-0745 TABLET, FILM COATED 100 mg ORAL NDA 19 sections
HYZAAR HUMAN PRESCRIPTION DRUG LABEL 2 0006-0747 TABLET, FILM COATED 100 mg ORAL NDA 19 sections
COZAAR HUMAN PRESCRIPTION DRUG LABEL 1 0006-0951 TABLET, FILM COATED 25 mg ORAL NDA 19 sections
COZAAR HUMAN PRESCRIPTION DRUG LABEL 1 0006-0952 TABLET, FILM COATED 50 mg ORAL NDA 19 sections
COZAAR HUMAN PRESCRIPTION DRUG LABEL 1 0006-0960 TABLET, FILM COATED 100 mg ORAL NDA 19 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0054-0123 TABLET 25 mg ORAL ANDA 19 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0054-0124 TABLET 50 mg ORAL ANDA 19 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0054-0125 TABLET 100 mg ORAL ANDA 19 sections
Losartan Potassium and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0093-7367 TABLET, FILM COATED 50 mg ORAL ANDA 18 sections
Losartan Potassium and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0093-7368 TABLET, FILM COATED 100 mg ORAL ANDA 18 sections
Losartan Potassium and Hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0093-7369 TABLET, FILM COATED 100 mg ORAL ANDA 18 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-7604 TABLET, FILM COATED 100 mg ORAL ANDA 13 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-7605 TABLET, FILM COATED 50 mg ORAL ANDA 13 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-7606 TABLET, FILM COATED 25 mg ORAL ANDA 13 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-7958 TABLET, FILM COATED 25 mg ORAL ANDA 20 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-7959 TABLET, FILM COATED 50 mg ORAL ANDA 20 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-7960 TABLET, FILM COATED 100 mg ORAL ANDA 20 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-8207 TABLET 25 mg ORAL ANDA 18 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-8208 TABLET 50 mg ORAL ANDA 18 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0615-8209 TABLET 100 mg ORAL ANDA 18 sections
Losartan potassium and hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0781-5204 TABLET, FILM COATED 100 mg ORAL ANDA 18 sections
Losartan potassium and hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0781-5206 TABLET, FILM COATED 50 mg ORAL ANDA 18 sections
Losartan potassium and hydrochlorothiazide HUMAN PRESCRIPTION DRUG LABEL 2 0781-5207 TABLET, FILM COATED 100 mg ORAL ANDA 18 sections
Losartan potassium HUMAN PRESCRIPTION DRUG LABEL 1 0781-5700 TABLET, FILM COATED 25 mg ORAL ANDA 19 sections
Losartan potassium HUMAN PRESCRIPTION DRUG LABEL 1 0781-5701 TABLET, FILM COATED 50 mg ORAL ANDA 19 sections
Losartan potassium HUMAN PRESCRIPTION DRUG LABEL 1 0781-5702 TABLET, FILM COATED 100 mg ORAL ANDA 19 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0904-6389 TABLET 100 mg ORAL ANDA 19 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0904-6390 TABLET 50 mg ORAL ANDA 19 sections
Losartan Potassium HUMAN PRESCRIPTION DRUG LABEL 1 0904-6391 TABLET 25 mg ORAL ANDA 19 sections