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

Stem definitionDrug idCAS RN
endopeptidase inhibitors 5012 149709-62-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • sacubitril
  • AHU377
  • sucabitril
inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite and leads to increased levels of peptides that are degraded by neprilysin such as natriuretic peptides
  • Molecular weight: 411.50
  • Formula: C24H29NO5
  • CLOGP: 4.47
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 92.70
  • ALOGS: -5.64
  • ROTB: 12

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Nov. 19, 2015 EMA
July 7, 2015 FDA NOVARTIS PHARMS CORP

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
Hypotension 1733.51 41.41 533 3790 31903 2321859
Dizziness 752.43 41.41 340 3983 58325 2295437
Cardiac failure 720.71 41.41 218 4105 11876 2341886
Dyspnoea 642.55 41.41 335 3988 78398 2275364
Cough 470.06 41.41 207 4116 32910 2320852
Death 447.55 41.41 268 4055 81200 2272562
Fatigue 411.74 41.41 258 4065 84615 2269147
Angioedema 376.09 41.41 122 4201 8274 2345488
Malaise 349.26 41.41 200 4123 55385 2298377
Blood pressure decreased 321.36 41.41 111 4212 9125 2344637
Pruritus 293.50 41.41 164 4159 43176 2310586
Blood potassium increased 289.24 41.41 74 4249 2122 2351640
Weight increased 253.96 41.41 120 4203 22217 2331545
Blood creatinine increased 248.25 41.41 95 4228 10438 2343324
No adverse event 242.82 41.41 91 4232 9437 2344325
Ejection fraction decreased 239.07 41.41 67 4256 2734 2351028
Contraindicated product administered 238.55 41.41 68 4255 2953 2350809
Hyperkalaemia 221.04 41.41 75 4248 5818 2347944
Rash 219.06 41.41 153 4170 59405 2294357
Wrong technique in product usage process 205.78 41.41 100 4223 19648 2334114
Acute kidney injury 205.20 41.41 112 4211 28010 2325752
Inappropriate schedule of product administration 194.09 41.41 83 4240 12121 2341641
Atrial fibrillation 190.88 41.41 85 4238 13683 2340079
Fluid retention 185.63 41.41 69 4254 6977 2346785
Renal impairment 185.14 41.41 76 4247 10016 2343746
Glomerular filtration rate decreased 180.39 41.41 47 4276 1446 2352316
Asthenia 173.28 41.41 121 4202 46805 2306957
Fall 161.26 41.41 116 4207 46983 2306779
Renal failure 151.53 41.41 78 4245 17271 2336491
Product prescribing error 148.59 41.41 47 4276 2913 2350849
Lip swelling 133.49 41.41 49 4274 4772 2348990
Weight decreased 133.04 41.41 85 4238 28286 2325476
Chest pain 121.35 41.41 80 4243 28057 2325705
Diarrhoea 117.83 41.41 124 4199 83440 2270322
Memory impairment 115.36 41.41 59 4264 12864 2340898
Feeling abnormal 113.86 41.41 72 4251 23509 2330253
Cardiac disorder 113.69 41.41 50 4273 7783 2345979
Concomitant disease aggravated 113.18 41.41 30 4293 986 2352776
Cardiac failure chronic 104.68 41.41 24 4299 425 2353337
Swelling face 101.46 41.41 49 4274 9444 2344318
Insomnia 98.41 41.41 68 4255 25719 2328043
Peripheral swelling 98.31 41.41 59 4264 17538 2336224
Weight fluctuation 94.39 41.41 24 4299 667 2353095
N-terminal prohormone brain natriuretic peptide increased 94.37 41.41 18 4305 121 2353641
Syncope 92.76 41.41 56 4267 16819 2336943
Arrhythmia 89.14 41.41 39 4284 5989 2347773
Gait disturbance 87.29 41.41 60 4263 22485 2331277
Blood urea increased 82.90 41.41 32 4291 3573 2350189
Cardiac failure congestive 82.26 41.41 51 4272 16050 2337712
Oedema 80.76 41.41 43 4280 10160 2343602
Prescribed underdose 80.18 41.41 27 4296 2035 2351727
Cardiogenic shock 78.97 41.41 28 4295 2463 2351299
Cerebrovascular accident 78.78 41.41 54 4269 20132 2333630
Renal disorder 76.11 41.41 32 4291 4456 2349306
Oedema peripheral 73.08 41.41 55 4268 23708 2330054
Underdose 69.87 41.41 33 4290 6045 2347717
Mitral valve incompetence 67.16 41.41 25 4298 2525 2351237
Nasopharyngitis 65.49 41.41 50 4273 22006 2331756
Confusional state 65.38 41.41 52 4271 24292 2329470
Device stimulation issue 64.61 41.41 9 4314 1 2353761
Gout 64.36 41.41 21 4302 1434 2352328
Dizziness postural 64.25 41.41 19 4304 935 2352827
Orthostatic hypotension 64.21 41.41 25 4298 2854 2350908
Nausea 64.17 41.41 107 4216 112082 2241680
Diabetes mellitus 63.31 41.41 33 4290 7462 2346300
Myocardial infarction 62.91 41.41 46 4277 18967 2334795
Basilar artery occlusion 61.86 41.41 10 4313 20 2353742
Palpitations 61.77 41.41 43 4280 16413 2337349
Hypersensitivity 60.38 41.41 49 4274 23544 2330218
Swollen tongue 58.32 41.41 28 4295 5315 2348447
Blood glucose increased 57.90 41.41 37 4286 12253 2341509
Product use in unapproved indication 55.97 41.41 35 4288 11165 2342597
General physical health deterioration 55.54 41.41 38 4285 14101 2339661
Orthopnoea 52.90 41.41 15 4308 635 2353127
Loss of consciousness 52.32 41.41 41 4282 18726 2335036
Chest discomfort 52.12 41.41 37 4286 14558 2339204
Hypertension 52.10 41.41 48 4275 27313 2326449
Heart rate increased 51.24 41.41 33 4290 11072 2342690
Left ventricular dysfunction 51.23 41.41 17 4306 1223 2352539
Urinary tract infection 50.29 41.41 49 4274 29893 2323869
Dehydration 50.18 41.41 43 4280 22252 2331510
Tricuspid valve incompetence 50.16 41.41 18 4305 1638 2352124
Drug intolerance 49.50 41.41 35 4288 13682 2340080
Brain natriuretic peptide increased 49.39 41.41 14 4309 592 2353170
Pain in extremity 47.40 41.41 56 4267 42484 2311278
Angina pectoris 46.89 41.41 22 4301 3965 2349797
Blood pressure increased 44.96 41.41 36 4287 16950 2336812
Pneumonia 43.90 41.41 58 4265 49238 2304524
Acute pulmonary oedema 43.09 41.41 15 4308 1248 2352514
Heart rate decreased 42.35 41.41 20 4303 3656 2350106
Abdominal discomfort 42.00 41.41 35 4288 17421 2336341
Pulmonary oedema 41.87 41.41 25 4298 7338 2346424
Drug ineffective 41.61 41.41 84 4239 101540 2252222

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
Hypotension 3942.44 48.71 1316 7941 28338 1709186
Dizziness 1695.33 48.71 747 8510 33614 1703910
Cardiac failure 1630.97 48.71 554 8703 12048 1725476
Dyspnoea 1269.90 48.71 701 8556 51358 1686166
Death 924.53 48.71 696 8561 86747 1650777
Blood pressure decreased 796.44 48.71 287 8970 7359 1730165
Fatigue 780.48 48.71 510 8747 50271 1687253
Blood creatinine increased 748.91 48.71 324 8933 13622 1723902
Cough 709.95 48.71 344 8913 18853 1718671
Hyperkalaemia 549.47 48.71 226 9031 8321 1729203
No adverse event 548.20 48.71 197 9060 4985 1732539
Contraindicated product administered 546.60 48.71 146 9111 1298 1736226
Weight increased 544.66 48.71 244 9013 11113 1726411
Blood potassium increased 529.16 48.71 161 9096 2369 1735155
Ejection fraction decreased 470.00 48.71 143 9114 2102 1735422
Renal failure 464.76 48.71 263 8994 19754 1717770
Wrong technique in product usage process 453.33 48.71 210 9047 10325 1727199
Acute kidney injury 441.26 48.71 312 8945 34632 1702892
Renal impairment 428.07 48.71 212 9045 12102 1725422
Malaise 408.16 48.71 279 8978 29286 1708238
Inappropriate schedule of product administration 401.55 48.71 174 9083 7285 1730239
Asthenia 383.82 48.71 286 8971 34384 1703140
Fluid retention 380.83 48.71 139 9118 3670 1733854
Angioedema 370.55 48.71 178 9079 9486 1728038
Product prescribing error 353.12 48.71 117 9140 2293 1735231
Syncope 352.41 48.71 195 9062 13974 1723550
Prescribed underdose 345.41 48.71 103 9154 1405 1736119
Weight decreased 333.34 48.71 223 9034 22530 1714994
Peripheral swelling 290.84 48.71 142 9115 7829 1729695
Diarrhoea 280.02 48.71 289 8968 53563 1683961
Cardiac failure chronic 276.01 48.71 72 9185 576 1736948
Ventricular tachycardia 266.06 48.71 107 9150 3691 1733833
Feeling abnormal 259.23 48.71 147 9110 11019 1726505
Pruritus 255.03 48.71 191 9066 23031 1714493
Blood pressure systolic decreased 247.48 48.71 67 9190 627 1736897
Glomerular filtration rate decreased 238.65 48.71 77 9180 1380 1736144
Atrial fibrillation 235.20 48.71 154 9103 14957 1722567
Cardiogenic shock 228.32 48.71 85 9172 2369 1735155
Fall 226.16 48.71 190 9067 27024 1710500
Oedema 212.83 48.71 110 9147 6838 1730686
Hypoacusis 211.89 48.71 81 9176 2432 1735092
Concomitant disease aggravated 183.55 48.71 54 9203 699 1736825
Rash 179.80 48.71 196 9061 38497 1699027
Oedema peripheral 179.64 48.71 132 9125 15418 1722106
Orthostatic hypotension 171.23 48.71 76 9181 3355 1734169
Chest pain 165.13 48.71 139 9118 19775 1717749
Myocardial infarction 157.33 48.71 155 9102 27019 1710505
Brain natriuretic peptide increased 152.66 48.71 44 9213 527 1736997
Dizziness postural 151.83 48.71 48 9209 802 1736722
Cardiac failure congestive 148.48 48.71 117 9140 15153 1722371
Pulmonary oedema 148.07 48.71 85 9172 6501 1731023
Product use in unapproved indication 146.35 48.71 96 9161 9326 1728198
Cerebrovascular accident 140.48 48.71 121 9136 17745 1719779
Blood urea increased 136.78 48.71 72 9185 4639 1732885
Cardiac disorder 135.87 48.71 85 9172 7606 1729918
Blood glucose increased 133.89 48.71 95 9162 10489 1727035
Lip swelling 133.33 48.71 60 9197 2735 1734789
Renal disorder 125.92 48.71 65 9192 4021 1733503
Loss of consciousness 125.62 48.71 105 9152 14770 1722754
Arrhythmia 125.57 48.71 74 9183 5942 1731582
Cardiac failure acute 123.94 48.71 45 9212 1164 1736360
Orthopnoea 122.88 48.71 38 9219 588 1736936
Memory impairment 121.11 48.71 75 9182 6588 1730936
Gait disturbance 120.79 48.71 96 9161 12574 1724950
Blood pressure fluctuation 120.35 48.71 45 9212 1267 1736257
Weight fluctuation 119.50 48.71 35 9222 445 1737079
Hypertension 118.17 48.71 114 9143 19334 1718190
Underdose 114.62 48.71 60 9197 3820 1733704
Left ventricular dysfunction 112.78 48.71 42 9215 1169 1736355
Chronic kidney disease 111.36 48.71 61 9196 4256 1733268
Sudden cardiac death 111.20 48.71 38 9219 818 1736706
Insomnia 107.61 48.71 100 9157 16176 1721348
N-terminal prohormone brain natriuretic peptide increased 106.98 48.71 24 9233 91 1737433
Mitral valve incompetence 106.54 48.71 46 9211 1896 1735628
Device malfunction 104.71 48.71 46 9211 1978 1735546
Therapeutic response unexpected 102.93 48.71 48 9209 2376 1735148
Nausea 102.21 48.71 172 9085 51024 1686500
Heart rate decreased 102.15 48.71 50 9207 2759 1734765
Dehydration 98.84 48.71 99 9158 17559 1719965
Blood pressure abnormal 98.70 48.71 37 9220 1049 1736475
Drug intolerance 97.09 48.71 63 9194 5999 1731525
Drug ineffective 96.49 48.71 190 9067 63611 1673913
Cardiorenal syndrome 95.48 48.71 21 9236 71 1737453
Pain in extremity 95.10 48.71 99 9158 18373 1719151
Sudden death 94.12 48.71 48 9209 2892 1734632
Gout 93.43 48.71 46 9211 2570 1734954
Chronic obstructive pulmonary disease 93.21 48.71 61 9196 5892 1731632
Pneumonia 90.59 48.71 154 9103 46028 1691496
Palpitations 88.05 48.71 62 9195 6752 1730772
Hypochromasia 86.60 48.71 17 9240 26 1737498
Blood creatine increased 84.17 48.71 30 9227 734 1736790
Tricuspid valve incompetence 83.37 48.71 34 9223 1212 1736312
Cardiac arrest 81.29 48.71 85 9172 15845 1721679
Hypervolaemia 80.23 48.71 20 9237 130 1737394
Heart rate irregular 79.65 48.71 36 9221 1656 1735868
Blood pressure increased 78.72 48.71 70 9187 10683 1726841
Pleural effusion 78.72 48.71 71 9186 11039 1726485
Left ventricular enlargement 77.50 48.71 16 9241 36 1737488
Left ventricular hypertrophy 77.32 48.71 29 9228 823 1736701
Nasopharyngitis 76.95 48.71 67 9190 9943 1727581
Swollen tongue 76.07 48.71 41 9216 2767 1734757
General physical health deterioration 76.04 48.71 75 9182 13043 1724481
Diabetes mellitus 75.94 48.71 57 9200 6851 1730673
Left atrial enlargement 75.76 48.71 16 9241 42 1737482
Acute pulmonary oedema 73.94 48.71 31 9226 1186 1736338
Mitral valve thickening 72.67 48.71 13 9244 7 1737517
Balance disorder 70.74 48.71 51 9206 5761 1731763
Ventricular hyperkinesia 69.77 48.71 13 9244 12 1737512
Hypertensive heart disease 69.77 48.71 23 9234 441 1737083
Joint swelling 68.89 48.71 52 9205 6301 1731223
Mean platelet volume increased 68.82 48.71 15 9242 48 1737476
Congestive cardiomyopathy 68.00 48.71 29 9228 1158 1736366
Swelling face 67.88 48.71 45 9212 4438 1733086
Right atrial enlargement 67.85 48.71 13 9244 16 1737508
Diastolic dysfunction 67.33 48.71 23 9234 494 1737030
Cardiomyopathy 65.78 48.71 37 9220 2715 1734809
Ventricular fibrillation 65.73 48.71 37 9220 2719 1734805
Ventricular arrhythmia 63.82 48.71 24 9233 686 1736838
Angina pectoris 63.29 48.71 45 9212 4973 1732551
Pulmonary hypertension 63.20 48.71 36 9221 2706 1734818
Swelling 62.34 48.71 51 9206 6945 1730579
Chest discomfort 62.32 48.71 52 9205 7279 1730245
Pollakiuria 58.20 48.71 35 9222 2911 1734613
Apparent death 57.98 48.71 18 9239 282 1737242
Blood uric acid increased 55.65 48.71 24 9233 985 1736539
Dyspnoea exertional 54.05 48.71 38 9219 4123 1733401
Heart rate increased 52.90 48.71 45 9212 6465 1731059
Blood chloride increased 52.83 48.71 17 9240 301 1737223
Ischaemic cardiomyopathy 52.70 48.71 24 9233 1123 1736401
C-reactive protein increased 52.63 48.71 43 9214 5842 1731682
Red cell distribution width increased 52.46 48.71 18 9239 392 1737132
Vision blurred 52.24 48.71 50 9207 8373 1729151
Influenza 51.39 48.71 45 9212 6722 1730802
Decreased appetite 49.86 48.71 82 9175 23789 1713735
Lethargy 49.07 48.71 45 9212 7139 1730385
Back pain 48.88 48.71 67 9190 16546 1720978

Pharmacologic Action:

SourceCodeDescription
ATC C09DX04 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
Angiotensin II receptor blockers (ARBs), other combinations

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic heart failure indication 48447003

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.05 acidic
pKa2 12.4 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
24MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 8796331 Jan. 14, 2023 TREATMENT OF HEART FAILURE
49MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 8796331 Jan. 14, 2023 TREATMENT OF HEART FAILURE
97MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 8796331 Jan. 14, 2023 TREATMENT OF HEART FAILURE
24MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
49MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
97MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
24MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL July 7, 2020 NEW CHEMICAL ENTITY
49MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL July 7, 2020 NEW CHEMICAL ENTITY
97MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL July 7, 2020 NEW CHEMICAL ENTITY
24MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Jan. 7, 2021 PEDIATRIC EXCLUSIVITY
49MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Jan. 7, 2021 PEDIATRIC EXCLUSIVITY
97MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Jan. 7, 2021 PEDIATRIC EXCLUSIVITY
24MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Oct. 1, 2022 NEW PATIENT POPULATION
49MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Oct. 1, 2022 NEW PATIENT POPULATION
97MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Oct. 1, 2022 NEW PATIENT POPULATION
24MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL April 1, 2023 PEDIATRIC EXCLUSIVITY
49MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL April 1, 2023 PEDIATRIC EXCLUSIVITY
97MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL April 1, 2023 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Neprilysin Enzyme INHIBITOR UNKNOWN DRUG LABEL

External reference:

IDSource
D10225 KEGG_DRUG
4034598 VUID
N0000191735 NUI
C4033447 UMLSCUI
17ERJ0MKGI UNII
9819 INN_ID
1656328 RXNORM
31106 MMSL
d08368 MMSL
016257 NDDF
4034598 VANDF
716072000 SNOMEDCT_US
9811834 PUBCHEM_CID
CHEBI:134714 CHEBI
DB09292 DRUGBANK_ID
CHEMBL3137301 ChEMBL_ID
7857 IUPHAR_LIGAND_ID
C000609743 MESH_SUPPLEMENTAL_RECORD_UI
C549068 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0659 TABLET, FILM COATED 24 mg ORAL NDA 19 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0696 TABLET, FILM COATED 97 mg ORAL NDA 19 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0777 TABLET, FILM COATED 49 mg ORAL NDA 19 sections