ivabradine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| bradycardic agents | 3312 | 155974-00-8 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Ivabradine is a pure heart rate lowering agent, acting by selective and specific inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates heart rate. The cardiac effects are specific to the sinus node with no effect on intra-atrial, atrioventricular or intraventricular conduction times, nor on myocardial contractility or ventricular repolarisation.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 10 | mg | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 1 | Benet LZ, Broccatelli F, Oprea TI |
| EoM (Fraction excreted unchanged in urine) | 4 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 0.46 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| Vd (Volume of distribution) | 1.66 L/kg | Lombardo F, Berellini G, Obach RS |
| CL (Clearance) | 10.27 mL/min/kg | Lombardo F, Berellini G, Obach RS |
| fu (Fraction unbound in plasma) | 0.28 % | Lombardo F, Berellini G, Obach RS |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Sept. 20, 2019 | PMDA | Ono Pharmaceutical Co., Ltd. | |
| April 15, 2015 | FDA | AMGEN INC | |
| Oct. 25, 2005 | EMA | Les Laboratoires Servier |
FDA Adverse Event Reporting System (Female)
| 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 |
|---|---|---|---|---|---|---|
| Off label use | 1208.97 | 54.73 | 330 | 570 | 73268 | 2283917 |
| Bradycardia | 207.75 | 54.73 | 56 | 844 | 9925 | 2347260 |
| Photopsia | 207.69 | 54.73 | 37 | 863 | 928 | 2356257 |
| Electrocardiogram QT prolonged | 163.09 | 54.73 | 44 | 856 | 7770 | 2349415 |
| Dizziness | 135.23 | 54.73 | 64 | 836 | 58601 | 2298584 |
| Torsade de pointes | 120.17 | 54.73 | 27 | 873 | 2219 | 2354966 |
| Chest pain | 118.16 | 54.73 | 47 | 853 | 28090 | 2329095 |
| Ischaemic stroke | 109.06 | 54.73 | 27 | 873 | 3370 | 2353815 |
| Dyspnoea | 103.57 | 54.73 | 59 | 841 | 78674 | 2278511 |
| Visual impairment | 103.47 | 54.73 | 34 | 866 | 11721 | 2345464 |
| Heart rate decreased | 101.99 | 54.73 | 26 | 874 | 3650 | 2353535 |
| Heart rate increased | 93.21 | 54.73 | 31 | 869 | 11074 | 2346111 |
| Syncope | 91.44 | 54.73 | 34 | 866 | 16841 | 2340344 |
| Palpitations | 77.70 | 54.73 | 30 | 870 | 16426 | 2340759 |
| Hypotension | 70.01 | 54.73 | 34 | 866 | 32402 | 2324783 |
| Headache | 66.68 | 54.73 | 45 | 855 | 80134 | 2277051 |
| Blood pressure decreased | 66.48 | 54.73 | 23 | 877 | 9213 | 2347972 |
| Ventricular tachycardia | 62.80 | 54.73 | 17 | 883 | 2994 | 2354191 |
| Drug interaction | 58.19 | 54.73 | 29 | 871 | 29134 | 2328051 |
| Malaise | 57.91 | 54.73 | 36 | 864 | 55549 | 2301636 |
| Tachycardia | 56.96 | 54.73 | 24 | 876 | 16385 | 2340800 |
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 |
|---|---|---|---|---|---|---|
| Off label use | 201.04 | 47.96 | 81 | 648 | 38490 | 1707562 |
| Cardiac failure | 158.22 | 47.96 | 51 | 678 | 12551 | 1733501 |
| Photopsia | 147.70 | 47.96 | 26 | 703 | 446 | 1745606 |
| Bradycardia | 121.29 | 47.96 | 40 | 689 | 10494 | 1735558 |
| Hypotension | 109.22 | 47.96 | 49 | 680 | 29605 | 1716447 |
| Bezoar | 93.93 | 47.96 | 15 | 714 | 136 | 1745916 |
| Oesophageal obstruction | 91.78 | 47.96 | 14 | 715 | 91 | 1745961 |
| Dyspnoea | 91.18 | 47.96 | 52 | 677 | 52007 | 1694045 |
| Chest pain | 66.96 | 47.96 | 31 | 698 | 19883 | 1726169 |
| Acute kidney injury | 66.55 | 47.96 | 37 | 692 | 34907 | 1711145 |
| Sinus bradycardia | 60.57 | 47.96 | 16 | 713 | 1917 | 1744135 |
| Presyncope | 59.77 | 47.96 | 17 | 712 | 2681 | 1743371 |
| Contraindicated product administered | 55.17 | 47.96 | 14 | 715 | 1430 | 1744622 |
| Lichenoid keratosis | 54.69 | 47.96 | 11 | 718 | 391 | 1745661 |
| Dizziness | 53.63 | 47.96 | 32 | 697 | 34329 | 1711723 |
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C01EB17 | CARDIOVASCULAR SYSTEM CARDIAC THERAPY OTHER CARDIAC PREPARATIONS Other cardiac preparations |
| ATC | C07FX05 | CARDIOVASCULAR SYSTEM BETA BLOCKING AGENTS BETA BLOCKING AGENTS, OTHER COMBINATIONS Beta blocking agents, other combinations |
| ATC | C07FX06 | CARDIOVASCULAR SYSTEM BETA BLOCKING AGENTS BETA BLOCKING AGENTS, OTHER COMBINATIONS Beta blocking agents, other combinations |
| FDA EPC | N0000191544 | Hyperpolarization-activated Cyclic Nucleotide-gated Channel Blocker |
| FDA MoA | N0000191546 | Hyperpolarization-activated Cyclic Nucleotide-gated Channel Antagonists |
| MeSH PA | D002317 | Cardiovascular Agents |
| CHEBI has role | CHEBI:38147 | cardiotonic drug |
Drug Use (View source of the data)
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Chronic heart failure | indication | 48447003 | |
| Angina pectoris | indication | 194828000 |
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 8.45 | Basic |
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 |
|---|---|---|---|---|---|---|---|---|---|---|
| EQ 5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7361649 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7361650 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7867996 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7879842 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 7.5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7361649 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 7.5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7361650 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 7.5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7867996 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| EQ 7.5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | 7879842 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | 7361649 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | 7361650 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | 7867996 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | 7879842 | Feb. 22, 2026 | A METHOD FOR TREATING HEART FAILURE IN A HUMAN USING A CRYSTALLINE FORM OF IVABRADINE HYDROCHLORIDE |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| EQ 5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | April 15, 2020 | NEW CHEMICAL ENTITY |
| EQ 7.5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | April 15, 2020 | NEW CHEMICAL ENTITY |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | April 15, 2020 | NEW CHEMICAL ENTITY |
| EQ 5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | Oct. 15, 2020 | PEDIATRIC EXCLUSIVITY |
| EQ 7.5MG BASE | CORLANOR | AMGEN INC | N206143 | April 15, 2015 | RX | TABLET | ORAL | Oct. 15, 2020 | PEDIATRIC EXCLUSIVITY |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | Oct. 15, 2020 | PEDIATRIC EXCLUSIVITY |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | April 22, 2022 | NEW PRODUCT |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | Oct. 22, 2022 | PEDIATRIC EXCLUSIVITY |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | April 22, 2026 | INDICATED FOR THE TREATMENT OF STABLE SYMPTOMATIC HEART FAILURE DUE TO DILATED CARDIOMYOPATHY (DCM) IN PEDIATRIC PATIENTS AGED 6 MONTHS AND OLDER, WHO ARE IN SINUS RHYTHM WITH AN ELEVATED HEART RATE |
| 5MG/5ML (1MG/ML) | CORLANOR | AMGEN INC | N209964 | April 22, 2019 | RX | SOLUTION | ORAL | Oct. 22, 2026 | PEDIATRIC EXCLUSIVITY |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | Ion channel | BLOCKER | IC50 | 5.70 | IUPHAR | DRUG LABEL | |||
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 | Ion channel | BLOCKER | UNKNOWN | DRUG LABEL | |||||
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 | Ion channel | BLOCKER | IC50 | 5.70 | IUPHAR | DRUG LABEL | |||
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | Ion channel | EC50 | 5.37 | CHEMBL | |||||
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 | Ion channel | EC50 | 5.34 | CHEMBL | |||||
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | Ion channel | EC50 | 5.35 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| D000077550 | MESH_DESCRIPTOR_UI |
| C4019965 | UMLSCUI |
| D07165 | KEGG_DRUG |
| 3H48L0LPZQ | UNII |
| 7523 | INN_ID |
| 421692002 | SNOMEDCT_US |
| 421228002 | SNOMEDCT_US |
| 011156 | NDDF |
| 1649480 | RXNORM |
| 4034416 | VANDF |
| d05706 | MMSL |
| CHEMBL471737 | ChEMBL_ID |
| 148849-67-6 | SECONDARY_CAS_RN |
| DB09083 | DRUGBANK_ID |
| CHEBI:85966 | CHEBI |
| CHEMBL2145077 | ChEMBL_ID |
| 132999 | PUBCHEM_CID |
| 2357 | IUPHAR_LIGAND_ID |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Corlanor | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55513-800 | TABLET, FILM COATED | 5 mg | ORAL | NDA | 19 sections |
| Corlanor | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55513-810 | TABLET, FILM COATED | 7.50 mg | ORAL | NDA | 19 sections |
| Corlanor | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55513-813 | SOLUTION | 5 mg | ORAL | NDA | 19 sections |