sacubitril 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| endopeptidase inhibitors | 5012 | 149709-62-6 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
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. It has been approved in combination with valsartan (under the name ENTRESTO) for the treatment of heart failure.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
None
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Nov. 19, 2015 | EMA | ||
| July 7, 2015 | FDA | NOVARTIS PHARMS CORP | |
| June 29, 2020 | PMDA | NOVARTIS PHARMA K.K. |
FDA Adverse Event Reporting System (Female)
None
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Cardiac failure | 90.15 | 50.42 | 38 | 498 | 91210 | 34865185 |
| Cardiac failure chronic | 52.84 | 50.42 | 14 | 522 | 7865 | 34948530 |
| Ventricular dysfunction | 51.80 | 50.42 | 12 | 524 | 3893 | 34952502 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Cardiac failure | 126.65 | 45.27 | 52 | 865 | 154790 | 79588681 |
| Cardiac failure chronic | 71.33 | 45.27 | 18 | 899 | 11117 | 79732354 |
| Ventricular dysfunction | 50.01 | 45.27 | 12 | 905 | 6011 | 79737460 |
| Hypotension | 46.32 | 45.27 | 39 | 878 | 440278 | 79303193 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| 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 | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Hypertensive disorder | indication | 38341003 | DOID:10763 |
| Chronic heart failure | indication | 48447003 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 4.05 | acidic |
| pKa2 | 12.4 | acidic |
Orange Book patent data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent use |
|---|---|---|---|---|---|---|---|---|---|---|
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 8796331 | Jan. 14, 2023 | TREATMENT OF HEART FAILURE |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 8796331 | Jan. 14, 2023 | TREATMENT OF HEART FAILURE |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 8796331 | Jan. 14, 2023 | TREATMENT OF HEART FAILURE |
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9388134 | Nov. 8, 2026 | TREATMENT OF HEART FAILURE |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9388134 | Nov. 8, 2026 | TREATMENT OF HEART FAILURE |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9388134 | Nov. 8, 2026 | TREATMENT OF HEART FAILURE |
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 11135192 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9517226 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9937143 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 11135192 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9517226 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9937143 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 11135192 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9517226 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 9937143 | Aug. 22, 2033 | TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION |
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 11058667 | May 9, 2036 | TREATING CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN PATIENTS NOT TAKING AN ACE INHIBITOR OR AN ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS, BY TITRATING UP FROM HALF THE USUALLY RECOMMENDED STARTING DOSE |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 11058667 | May 9, 2036 | TREATING CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN PATIENTS NOT TAKING AN ACE INHIBITOR OR AN ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS, BY TITRATING UP FROM HALF THE USUALLY RECOMMENDED STARTING DOSE |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | 11058667 | May 9, 2036 | TREATING CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN PATIENTS NOT TAKING AN ACE INHIBITOR OR AN ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS, BY TITRATING UP FROM HALF THE USUALLY RECOMMENDED STARTING DOSE |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | April 1, 2023 | PEDIATRIC EXCLUSIVITY |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | April 1, 2023 | PEDIATRIC EXCLUSIVITY |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | April 1, 2023 | PEDIATRIC EXCLUSIVITY |
| 24MG;26MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | Feb. 16, 2024 | LABELING REVISIONS RELATED TO CLINICAL STUDIES |
| 49MG;51MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | Feb. 16, 2024 | LABELING REVISIONS RELATED TO CLINICAL STUDIES |
| 97MG;103MG | ENTRESTO | NOVARTIS PHARMS CORP | N207620 | July 7, 2015 | RX | TABLET | ORAL | Feb. 16, 2024 | LABELING REVISIONS RELATED TO CLINICAL STUDIES |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Neprilysin | Enzyme | INHIBITOR | IC50 | 8.22 | CHEMBL | DRUG LABEL | |||
| Neprilysin | Enzyme | IC50 | 8.30 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 17ERJ0MKGI | UNII |
| D10225 | KEGG_DRUG |
| 4034598 | VUID |
| N0000191735 | NUI |
| 4034598 | VANDF |
| C4033447 | UMLSCUI |
| CHEBI:134714 | CHEBI |
| 6LD | PDB_CHEM_ID |
| CHEMBL3137301 | ChEMBL_ID |
| 9811834 | PUBCHEM_CID |
| DB09292 | DRUGBANK_ID |
| 9819 | INN_ID |
| C000717211 | MESH_SUPPLEMENTAL_RECORD_UI |
| 7857 | IUPHAR_LIGAND_ID |
| C000609743 | MESH_SUPPLEMENTAL_RECORD_UI |
| 1656328 | RXNORM |
| 31106 | MMSL |
| d08368 | MMSL |
| 016257 | NDDF |
| 716072000 | SNOMEDCT_US |
| D10226 | KEGG_DRUG |
| C4277755 | UMLSCUI |
| CHEMBL417007 | ChEMBL_ID |
| 10430040 | PUBCHEM_CID |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-0659 | TABLET, FILM COATED | 24 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-0659 | TABLET, FILM COATED | 24 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-0696 | TABLET, FILM COATED | 97 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-0696 | TABLET, FILM COATED | 97 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-0777 | TABLET, FILM COATED | 49 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-0777 | TABLET, FILM COATED | 49 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-9659 | TABLET, FILM COATED | 24 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-9659 | TABLET, FILM COATED | 24 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-9777 | TABLET, FILM COATED | 49 mg | ORAL | NDA | 34 sections |
| ENTRESTO | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0078-9777 | TABLET, FILM COATED | 49 mg | ORAL | NDA | 34 sections |