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Stem definition	Drug id	CAS RN
bradycardic agents	3312	155974-00-8

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: corlanor corlentor ivabradine hydrochloride ivabradine coraxan procoralan ivabradine HCl	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. Molecular weight: 468.59 Formula: C27H36N2O5 CLOGP: 3.07 LIPINSKI: 0 HAC: 7 HDO: 0 TPSA: 60.47 ALOGS: -4.36 ROTB: 10 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

corlanor
corlentor
ivabradine hydrochloride
ivabradine
coraxan
procoralan
ivabradine HCl

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.

Molecular weight: 468.59
Formula: C27H36N2O5
CLOGP: 3.07
LIPINSKI: 0
HAC: 7
HDO: 0
TPSA: 60.47
ALOGS: -4.36
ROTB: 10

Status: OFP

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
BA (Bioavailability)	40 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	1.427		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	10.471		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	7.816	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	16.943	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	37.650	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	58.720	%	High	1
herg	hERG pIC50	5.360	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	3.673	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	100.693	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	31.070	%	High	1
kinase-safety-class	ACVR2A,ACVR2B,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPKAPK2,MET,MTOR,NTRK2,PAK4,PDK2,PDK4,PIK3CB,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK	43
kinase-selectivity-class	AXL,EIF2AK3,EPHB4,ERBB2,GRK2,PDK4,PIK3CB,PRKDC,SIK2,TEK,TTK	11
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	8.356		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	53.211		High	1
mppb	Mouse plasma protein binding (% unbound)	32.930		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	26.303		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pppb	Pig plasma protein binding (% unbound)	59.990	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	32.659	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	73	%	High	1
rppb	Rat plasma protein binding (% unbound)	31.120	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	963.829	uM	High	1

Approvals:

Date	Agency	Company
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	343.61	18.42	539	10726	1101713	89515469
Bradycardia	189.11	18.42	122	11143	83725	90533457
Drug interaction	168.64	18.42	189	11076	276264	90340918
Photopsia	165.50	18.42	49	11216	4975	90612207
Cardiac failure	140.22	18.42	113	11152	109383	90507799
Electrocardiogram QT prolonged	110.59	18.42	83	11182	72373	90544809
Torsade de pointes	109.32	18.42	48	11217	15134	90602048
Palpitations	109.08	18.42	108	11157	136620	90480562
Syncope	104.36	18.42	104	11161	132559	90484623
Ischaemic stroke	94.89	18.42	49	11216	22117	90595065
Hypotension	77.24	18.42	142	11123	325255	90291927
Apallic syndrome	70.60	18.42	17	11248	779	90616403
Congestive cardiomyopathy	68.76	18.42	28	11237	7326	90609856
Dizziness	64.00	18.42	189	11076	589095	90028087
Ventricular fibrillation	62.86	18.42	32	11233	14012	90603170
First trimester pregnancy	60.70	18.42	8	11257	4	90617178
Heart rate decreased	59.63	18.42	51	11214	53454	90563728
Myoglobin blood increased	59.34	18.42	17	11248	1535	90615647
Endocarditis enterococcal	59.09	18.42	12	11253	247	90616935
Cardiac failure chronic	57.99	18.42	23	11242	5623	90611559
Chest pain	57.18	18.42	124	11141	319521	90297661
Drug effective for unapproved indication	56.88	18.42	25	11240	7893	90609289
Orthopnoea	53.74	18.42	23	11242	6812	90610370
Serum amyloid A protein increased	51.87	18.42	13	11252	704	90616478
Sinus bradycardia	51.82	18.42	30	11235	16922	90600260
Respiratory syncytial virus test positive	51.49	18.42	14	11251	1044	90616138
Mitral valve replacement	50.87	18.42	12	11253	503	90616679
Ventricular tachycardia	50.86	18.42	34	11231	24674	90592508
Bundle branch block left	47.45	18.42	22	11243	7863	90609319
Crush syndrome	45.66	18.42	10	11255	299	90616883
Vascular stent stenosis	42.71	18.42	11	11254	665	90616517
Language disorder	42.61	18.42	15	11250	2637	90614545
Dyspnoea	42.14	18.42	218	11047	880737	89736445
Pain	41.28	18.42	38	11227	996303	89620879
Acute kidney injury	40.79	18.42	109	11156	320278	90296904
Aortic valve replacement	39.01	18.42	11	11254	938	90616244
Angina pectoris	38.95	18.42	35	11230	39125	90578057
Heart rate increased	38.42	18.42	58	11207	112844	90504338
Ejection fraction decreased	37.65	18.42	29	11236	26224	90590958
Sensorimotor disorder	36.79	18.42	10	11255	745	90616437
Tachycardia	36.30	18.42	68	11197	157605	90459577
Joint swelling	36.24	18.42	9	11256	503291	90113891
Visual impairment	35.47	18.42	61	11204	132304	90484878
Pneumobilia	33.60	18.42	7	11258	164	90617018
Mitral valve incompetence	32.56	18.42	25	11240	22499	90594683
Vision blurred	32.45	18.42	53	11212	110240	90506942
Ventricular hypokinesia	32.44	18.42	15	11250	5326	90611856
Bronchospasm	32.18	18.42	24	11241	20685	90596497
Arrhythmia	31.06	18.42	32	11233	42300	90574882
Cardiogenic shock	30.73	18.42	25	11240	24443	90592739
Varices oesophageal	30.64	18.42	13	11252	3766	90613416
Angioedema	30.58	18.42	39	11226	64837	90552345
Alopecia	30.03	18.42	12	11253	495059	90122123
Postural orthostatic tachycardia syndrome	29.57	18.42	11	11254	2261	90614921
Genital rash	28.81	18.42	8	11257	645	90616537
Spinal pain	28.43	18.42	20	11245	15747	90601435
Hyperparathyroidism secondary	28.22	18.42	10	11255	1791	90615391
Gastric antral vascular ectasia	26.92	18.42	8	11257	821	90616361
Agranulocytosis	26.66	18.42	27	11238	34975	90582207
Shock haemorrhagic	25.56	18.42	17	11248	12228	90604954
Oliguria	25.24	18.42	16	11249	10608	90606574
Serotonin syndrome	24.88	18.42	27	11238	37860	90579322
Hyperphosphataemia	24.35	18.42	11	11254	3700	90613482
Therapeutic product effect decreased	24.22	18.42	3	11262	277568	90339614
Haematoma	24.21	18.42	27	11238	39021	90578161
Acute pulmonary oedema	24.20	18.42	15	11250	9565	90607617
Lordosis	23.87	18.42	6	11259	329	90616853
Infusion related reaction	23.83	18.42	11	11254	416769	90200413
Intentional overdose	23.52	18.42	42	11223	93792	90523390
Blood pressure decreased	23.40	18.42	37	11228	74858	90542324
Tuberculosis of central nervous system	23.37	18.42	6	11259	358	90616824
Tracheal atresia	23.30	18.42	4	11261	31	90617151
Gastrointestinal tract adenoma	23.07	18.42	6	11259	377	90616805
Pneumonia fungal	22.98	18.42	13	11252	7018	90610164
Abdominal discomfort	22.45	18.42	16	11249	477312	90139870
Metabolic acidosis	22.43	18.42	31	11234	55645	90561537
Drug ineffective for unapproved indication	22.32	18.42	34	11231	66610	90550572
Shrinking lung syndrome	22.21	18.42	5	11260	170	90617012
Lactic acidosis	21.70	18.42	29	11236	50434	90566748
Systemic lupus erythematosus	21.56	18.42	9	11256	361887	90255295
Hyperkalaemia	21.56	18.42	33	11232	64931	90552251
Nasopharyngitis	21.40	18.42	12	11253	407092	90210090
Cardiac arrest	21.38	18.42	43	11222	104892	90512290
Tachypnoea	21.10	18.42	19	11246	21290	90595892
Anaemia folate deficiency	20.96	18.42	6	11259	540	90616642
Femoral neck fracture	20.86	18.42	14	11251	10219	90606963
Lethargy	20.85	18.42	32	11233	63107	90554075
Osteochondrosis	20.66	18.42	8	11257	1835	90615347
Lupus myocarditis	20.42	18.42	4	11261	68	90617114
Hypersensitivity	20.40	18.42	16	11249	454661	90162521
Mydriasis	20.26	18.42	16	11249	14996	90602186
Rheumatoid arthritis	20.07	18.42	10	11255	362604	90254578
Atrial fibrillation	19.60	18.42	48	11217	133563	90483619
Sinus arrest	19.48	18.42	8	11257	2138	90615044
Treatment failure	19.02	18.42	7	11258	303921	90313261
Bleeding varicose vein	18.48	18.42	5	11260	366	90616816

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	362.31	20.19	263	10641	106593	42503838
Bradycardia	169.26	20.19	154	10750	85330	42525101
Hypotension	141.42	20.19	243	10661	257388	42353043
Ischaemic cardiomyopathy	105.02	20.19	45	10859	6477	42603954
Photopsia	95.28	20.19	32	10872	2360	42608071
Ventricular dysfunction	92.58	20.19	37	10867	4466	42605965
Computerised tomogram coronary artery abnormal	92.41	20.19	18	10886	135	42610296
Cardiac failure chronic	91.32	20.19	46	10858	9555	42600876
N-terminal prohormone brain natriuretic peptide increased	73.17	20.19	29	10875	3424	42607007
Dyspnoea	71.20	20.19	261	10643	442360	42168071
Asthma-chronic obstructive pulmonary disease overlap syndrome	70.68	20.19	23	10881	1536	42608895
Dyspnoea at rest	67.35	20.19	29	10875	4220	42606211
Pulmonary oedema	66.70	20.19	75	10829	53197	42557234
Cardiomyopathy	66.39	20.19	48	10856	19162	42591269
Bronchial hyperreactivity	65.88	20.19	23	10881	1906	42608525
Presyncope	64.16	20.19	50	10854	22337	42588094
Ejection fraction decreased	62.58	20.19	49	10855	22038	42588393
Oedema peripheral	58.74	20.19	116	10788	135960	42474471
Pulmonary function test abnormal	58.39	20.19	23	10881	2671	42607760
Sinus bradycardia	58.02	20.19	40	10864	14813	42595618
Venous pressure jugular increased	54.52	20.19	16	10888	756	42609675
Oesophageal obstruction	53.85	20.19	15	10889	587	42609844
Torsade de pointes	53.27	20.19	31	10873	8563	42601868
Electrocardiogram abnormal	51.02	20.19	32	10872	10113	42600318
Ventricular arrhythmia	50.83	20.19	27	10877	6252	42604179
Ventricular extrasystoles	49.81	20.19	35	10869	13355	42597076
Left ventricular enlargement	49.05	20.19	15	10889	817	42609614
Bezoar	46.61	20.19	16	10888	1260	42609171
Hyperkalaemia	45.32	20.19	77	10827	80381	42530050
Blood pressure systolic decreased	44.81	20.19	23	10881	4964	42605467
Drug interaction	43.18	20.19	158	10746	266841	42343590
Dyspnoea exertional	42.43	20.19	58	10846	50090	42560341
Base excess decreased	42.32	20.19	10	10894	200	42610231
Ventricular tachycardia	42.13	20.19	45	10859	30115	42580316
Blood potassium increased	37.76	20.19	34	10870	18502	42591929
Venous pressure jugular decreased	37.73	20.19	7	10897	39	42610392
Glomerular filtration rate decreased	37.33	20.19	32	10872	16319	42594112
Eosinophilia	37.25	20.19	44	10860	32855	42577576
Breath sounds abnormal	36.80	20.19	28	10876	12065	42598366
Angina pectoris	35.61	20.19	43	10861	32853	42577578
Tricuspid valve incompetence	34.41	20.19	26	10878	11087	42599344
Atrial tachycardia	34.07	20.19	18	10886	4122	42606309
Oxygen consumption decreased	33.64	20.19	9	10895	302	42610129
Brain natriuretic peptide increased	33.15	20.19	21	10883	6749	42603682
Product prescribing error	31.36	20.19	36	10868	26076	42584355
Mitral valve incompetence	31.15	20.19	29	10875	16460	42593971
Bronchial wall thickening	30.84	20.19	12	10892	1348	42609083
Death	30.49	20.19	46	10858	471139	42139292
Fluid retention	30.48	20.19	39	10865	31580	42578851
Blood creatinine increased	29.77	20.19	78	10826	109925	42500506
Urticaria chronic	29.12	20.19	7	10897	151	42610280
Concomitant disease aggravated	28.73	20.19	19	10885	6567	42603864
Left ventricular dilatation	27.88	20.19	10	10894	896	42609535
Cardiac failure acute	27.75	20.19	25	10879	13608	42596823
Syncope	27.42	20.19	71	10833	99335	42511096
ECG signs of myocardial ischaemia	27.31	20.19	7	10897	198	42610233
Ventricular enlargement	26.65	20.19	9	10895	674	42609757
Palpitations	26.47	20.19	47	10857	50750	42559681
Dermatitis exfoliative generalised	25.89	20.19	17	10887	5807	42604624
Sinus arrest	25.52	20.19	12	10892	2144	42608287
Diastolic dysfunction	25.38	20.19	18	10886	6965	42603466
Serum amyloid A protein increased	25.35	20.19	7	10897	265	42610166
Hypertrophy	25.02	20.19	8	10896	505	42609926
Body mass index increased	24.98	20.19	10	10894	1211	42609220
Tracheal atresia	24.69	20.19	4	10900	8	42610423
Dizziness	24.45	20.19	127	10777	249127	42361304
Cardiac ventricular thrombosis	24.24	20.19	11	10893	1811	42608620
Non-compaction cardiomyopathy	23.95	20.19	5	10899	55	42610376
Congestive cardiomyopathy	23.86	20.19	19	10885	8745	42601686
Acute kidney injury	23.82	20.19	168	10736	367169	42243262
Low cardiac output syndrome	23.11	20.19	8	10896	646	42609785
Left ventricular hypertrophy	22.83	20.19	19	10885	9300	42601131
Psoriasis	22.83	20.19	43	10861	48561	42561870
Contraindicated product administered	22.53	20.19	30	10874	25242	42585189
Blood luteinising hormone increased	21.66	20.19	5	10899	90	42610341
Supraventricular extrasystoles	21.06	20.19	13	10891	3993	42606438
Acute myocardial infarction	20.84	20.19	46	10858	58119	42552312
Oesophageal haemorrhage	20.29	20.19	9	10895	1405	42609026

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	488.43	16.05	349	20449	187277	110381224
Bradycardia	334.22	16.05	258	20540	155259	110413242
Off label use	242.35	16.05	721	20077	1499464	109069037
Hypotension	209.31	16.05	362	20436	523487	110045014
Photopsia	197.47	16.05	65	20733	6149	110562352
Drug interaction	193.71	16.05	341	20457	499842	110068659
Torsade de pointes	156.26	16.05	79	20719	22521	110545980
Cardiac failure chronic	146.98	16.05	65	20733	13746	110554755
Ischaemic cardiomyopathy	116.25	16.05	47	20751	7964	110560537
Syncope	112.44	16.05	163	20635	202373	110366128
Dyspnoea	104.17	16.05	447	20351	1106425	109462076
Computerised tomogram coronary artery abnormal	97.82	16.05	18	20780	136	110568365
Ventricular tachycardia	96.53	16.05	78	20720	49931	110518570
Ejection fraction decreased	94.62	16.05	71	20727	40809	110527692
Palpitations	94.02	16.05	132	20666	159080	110409421
Sinus bradycardia	93.31	16.05	62	20736	29421	110539080
Electrocardiogram QT prolonged	88.87	16.05	106	20692	108854	110459647
N-terminal prohormone brain natriuretic peptide increased	85.69	16.05	35	20763	6086	110562415
Cardiomyopathy	79.31	16.05	59	20739	33466	110535035
Ventricular dysfunction	78.79	16.05	35	20763	7476	110561025
Presyncope	77.34	16.05	68	20730	48819	110519682
Serum amyloid A protein increased	74.72	16.05	20	20778	922	110567579
Ischaemic stroke	74.68	16.05	62	20736	41201	110527300
Dizziness	74.12	16.05	293	20505	697900	109870601
Congestive cardiomyopathy	73.64	16.05	41	20757	14178	110554323
Acute kidney injury	71.78	16.05	272	20526	635158	109933343
Bronchial hyperreactivity	69.94	16.05	26	20772	3518	110564983
Ventricular extrasystoles	65.40	16.05	45	20753	22596	110545905
Hyperkalaemia	64.93	16.05	102	20696	135694	110432807
Ventricular fibrillation	64.42	16.05	57	20741	41256	110527245
Mitral valve incompetence	62.23	16.05	51	20747	33278	110535223
Left ventricular enlargement	62.09	16.05	17	20781	854	110567647
Ventricular arrhythmia	60.33	16.05	32	20766	10055	110558446
Dyspnoea at rest	60.10	16.05	30	20768	8316	110560185
Chest pain	59.07	16.05	180	20618	376195	110192306
Apallic syndrome	58.07	16.05	17	20781	1089	110567412
Pulmonary function test abnormal	57.96	16.05	25	20773	4975	110563526
Orthopnoea	57.68	16.05	32	20766	10989	110557512
First trimester pregnancy	57.39	16.05	8	20790	4	110568497
Angina pectoris	56.45	16.05	64	20734	62231	110506270
Pain	55.27	16.05	59	20739	954896	109613605
Dyspnoea exertional	52.30	16.05	80	20718	103980	110464521
Asthma-chronic obstructive pulmonary disease overlap syndrome	52.27	16.05	25	20773	6319	110562182
Pulmonary oedema	51.46	16.05	78	20720	100581	110467920
Bundle branch block left	50.45	16.05	31	20767	12857	110555644
Endocarditis enterococcal	49.65	16.05	12	20786	365	110568136
ECG signs of myocardial ischaemia	48.14	16.05	12	20786	416	110568085
Drug effective for unapproved indication	47.76	16.05	31	20767	14136	110554365
Oesophageal obstruction	47.66	16.05	15	20783	1228	110567273
Glomerular filtration rate decreased	47.25	16.05	41	20757	28915	110539586
Eosinophilia	46.62	16.05	56	20742	57880	110510621
Venous pressure jugular increased	46.42	16.05	15	20783	1337	110567164
Atrial tachycardia	46.26	16.05	26	20772	9152	110559349
Joint swelling	46.26	16.05	13	20785	442832	110125669
Oedema peripheral	45.88	16.05	151	20647	328509	110239992
Mitral valve replacement	43.61	16.05	12	20786	614	110567887
Tricuspid valve incompetence	43.46	16.05	36	20762	23837	110544664
Electrocardiogram abnormal	42.18	16.05	32	20766	18677	110549824
Infusion related reaction	42.08	16.05	10	20788	381152	110187349
Brain natriuretic peptide increased	41.44	16.05	26	20772	11183	110557318
Respiratory syncytial virus test positive	41.01	16.05	14	20784	1480	110567021
Hepatic enzyme increased	40.57	16.05	6	20792	320886	110247615
Blood pressure systolic decreased	39.49	16.05	27	20771	13414	110555087
Crush syndrome	39.10	16.05	10	20788	385	110568116
Cardiac failure acute	39.09	16.05	34	20764	24044	110544457
Base excess decreased	38.88	16.05	10	20788	394	110568107
Musculoskeletal stiffness	38.37	16.05	4	20794	279818	110288683
Acute myocardial infarction	37.38	16.05	61	20737	83716	110484785
Arthropathy	37.23	16.05	5	20793	287517	110280984
Blood potassium increased	36.85	16.05	38	20760	33211	110535290
Ventricular hypokinesia	36.49	16.05	24	20774	11190	110557311
Rhabdomyolysis	36.34	16.05	74	20724	120327	110448174
Myoglobin blood increased	35.85	16.05	17	20781	4215	110564286
Nasopharyngitis	35.28	16.05	15	20783	394346	110174155
Abdominal discomfort	35.20	16.05	15	20783	393843	110174658
Blood creatinine increased	34.99	16.05	94	20704	182795	110385706
Venous pressure jugular decreased	34.81	16.05	7	20791	88	110568413
Arrhythmia	34.26	16.05	53	20745	69522	110498979
Bezoar	33.47	16.05	16	20782	4038	110564463
Sinus arrest	32.78	16.05	16	20782	4226	110564275
Heart rate decreased	32.60	16.05	57	20741	82699	110485802
Aortic valve replacement	32.35	16.05	12	20786	1614	110566887
Diastolic dysfunction	31.98	16.05	23	20775	12381	110556120
Breath sounds abnormal	31.77	16.05	31	20767	25373	110543128
Oxygen consumption decreased	31.66	16.05	9	20789	519	110567982
Blood pressure decreased	31.54	16.05	68	20730	115023	110453478
Body mass index increased	31.51	16.05	13	20785	2317	110566184
Language disorder	31.24	16.05	15	20783	3823	110564678
Rheumatoid arthritis	30.89	16.05	9	20789	299604	110268897
Acute pulmonary oedema	29.63	16.05	25	20773	16971	110551530
Intentional overdose	29.37	16.05	72	20726	132429	110436072
Low cardiac output syndrome	28.94	16.05	10	20788	1096	110567405
Ventricular enlargement	28.86	16.05	9	20789	715	110567786
Sinusitis	28.66	16.05	10	20788	296678	110271823
Drug hypersensitivity	28.56	16.05	26	20772	454064	110114437
Sensorimotor disorder	28.37	16.05	10	20788	1162	110567339
Product prescribing error	27.97	16.05	41	20757	51290	110517211
Alopecia	27.95	16.05	17	20781	364736	110203765
Cardiac ventricular thrombosis	27.76	16.05	13	20785	3134	110565367
Dyspnoea paroxysmal nocturnal	27.34	16.05	12	20786	2490	110566011
Osteochondrosis	27.25	16.05	12	20786	2509	110565992
Rash	26.87	16.05	73	20725	820891	109747610
Cardiac disorder	26.81	16.05	50	20748	76230	110492271
Hypersensitivity	26.78	16.05	22	20776	403976	110164525
Haematoma	26.66	16.05	43	20755	58433	110510068
Wound	26.16	16.05	6	20792	234431	110334070
Pneumobilia	26.14	16.05	7	20791	323	110568178
Vertigo	25.74	16.05	53	20745	86817	110481684
Systemic lupus erythematosus	25.56	16.05	8	20790	254330	110314171
Atrial fibrillation	25.56	16.05	98	20700	229544	110338957
Gastrointestinal disorder	25.44	16.05	7	20791	241945	110326556
Dermatitis exfoliative generalised	25.25	16.05	19	20779	10953	110557548
Non-compaction cardiomyopathy	25.16	16.05	5	20793	59	110568442
Feeling abnormal	25.16	16.05	83	20715	180628	110387873
Acute coronary syndrome	24.86	16.05	26	20772	23086	110545415
Stomatitis	24.61	16.05	10	20788	270232	110298269
Lactic acidosis	24.47	16.05	54	20744	92757	110475744
Urticaria chronic	24.26	16.05	8	20790	760	110567741
Impaired healing	24.12	16.05	4	20794	196713	110371788
Spinal pain	23.91	16.05	23	20775	18492	110550009
Exercise tolerance decreased	23.65	16.05	19	20779	12048	110556453
Vitreous detachment	23.48	16.05	11	20787	2654	110565847
Hypertrophy	22.72	16.05	8	20790	927	110567574
Mean cell haemoglobin decreased	22.48	16.05	15	20783	7159	110561342
Angina unstable	22.34	16.05	21	20777	16411	110552090
Swelling	22.19	16.05	20	20778	351021	110217480
Left ventricular hypertrophy	22.10	16.05	19	20779	13225	110555276
Bronchial wall thickening	21.55	16.05	11	20787	3196	110565305
Circulatory collapse	21.51	16.05	33	20765	42960	110525541
Infection	21.30	16.05	22	20776	362178	110206323
Left ventricular dysfunction	21.04	16.05	24	20774	23469	110545032
Wrong technique in product usage process	21.00	16.05	49	20749	87299	110481202
Hypoaesthesia	20.96	16.05	17	20781	314206	110254295
Irritable bowel syndrome	20.91	16.05	3	20795	164212	110404289
Supraventricular extrasystoles	20.88	16.05	15	20783	8058	110560443
Heart rate increased	20.86	16.05	67	20731	143767	110424734
Arthralgia	20.80	16.05	76	20722	779556	109788945
Gastric antral vascular ectasia	20.79	16.05	8	20790	1189	110567312
Cardiogenic shock	20.67	16.05	38	20760	57300	110511201
International normalised ratio decreased	20.61	16.05	15	20783	8221	110560280
Oesophageal haemorrhage	20.38	16.05	9	20789	1894	110566607
Left ventricular failure	20.36	16.05	17	20781	11372	110557129
Sudden death	20.31	16.05	24	20774	24371	110544130
Shrinking lung syndrome	20.07	16.05	5	20793	173	110568328
Genital rash	19.94	16.05	8	20790	1327	110567174
Mobility decreased	19.72	16.05	10	20788	237412	110331089
Left ventricular dilatation	19.46	16.05	8	20790	1414	110567087
Lordosis	19.36	16.05	6	20792	467	110568034
Conduction disorder	19.12	16.05	11	20787	4044	110564457
Visual impairment	18.93	16.05	62	20736	134366	110434135
Myoclonus	18.92	16.05	27	20771	32971	110535530
Blood luteinising hormone increased	18.90	16.05	5	20793	220	110568281
Atrioventricular block complete	18.81	16.05	21	20777	20061	110548440
Abdominal pain	18.80	16.05	43	20755	512946	110055555
Kyphosis	18.75	16.05	10	20788	3177	110565324
Concomitant disease aggravated	18.67	16.05	19	20779	16345	110552156
Tuberculosis of central nervous system	18.61	16.05	6	20792	531	110567970
Atrioventricular block second degree	18.46	16.05	14	20784	8167	110560334
Hyperparathyroidism secondary	18.41	16.05	10	20788	3294	110565207
Intentional product use issue	18.37	16.05	12	20786	247894	110320607
Atrioventricular block	18.18	16.05	19	20779	16858	110551643
Gastrointestinal tract adenoma	18.08	16.05	6	20792	581	110567920
Wheezing	18.05	16.05	13	20785	255217	110313284
Tachycardia	17.75	16.05	87	20711	226558	110341943
Varices oesophageal	17.74	16.05	13	20785	7202	110561299
Bronchospasm	17.71	16.05	25	20773	30214	110538287
Lupus myocarditis	17.50	16.05	4	20794	95	110568406
Serotonin syndrome	17.42	16.05	36	20762	59117	110509384
Arthritis	17.33	16.05	5	20793	167581	110400920
Postural orthostatic tachycardia syndrome	17.30	16.05	8	20790	1874	110566627
Anaemia folate deficiency	17.04	16.05	6	20792	695	110567806
Iron deficiency anaemia	16.89	16.05	25	20773	31534	110536967
Orthostatic hypotension	16.85	16.05	38	20760	66211	110502290
Blood chloride increased	16.85	16.05	12	20786	6360	110562141
Metabolic acidosis	16.83	16.05	49	20749	99695	110468806
Psoriatic arthropathy	16.77	16.05	8	20790	196753	110371748
Eye movement disorder	16.32	16.05	14	20784	9714	110558787
Completed suicide	16.30	16.05	13	20785	242368	110326133
Extrasystoles	16.10	16.05	13	20785	8305	110560196

FDA Adverse Event Reporting System (Pediatric)

None

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
MeSH PA	D002317	Cardiovascular Agents
FDA EPC	N0000191544	Hyperpolarization-activated Cyclic Nucleotide-gated Channel Blocker
FDA MoA	N0000191546	Hyperpolarization-activated Cyclic Nucleotide-gated Channel Antagonists
CHEBI has role	CHEBI:35526	hypoglycemic agent
CHEBI has role	CHEBI:35554	cardiovascular drug
CHEBI has role	CHEBI:35610	antineoplastic agent
CHEBI has role	CHEBI:38070	anti-arrhythmia drug
CHEBI has role	CHEBI:38147	cardiotonic drug
CHEBI has role	CHEBI:50514	vasoconstrictor agent
CHEBI has role	CHEBI:149553	anticoronaviral agent
CHEBI has role	CHEBI:176497	geroprotector

Related Drugs by ATC class:

C01EB Other cardiac preparations 15 drugs

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C07FX Beta blocking agents, other combinations 6 drugs

acetylsalicylic acid bisoprolol carvedilol metoprolol propranolol sotalol

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Chronic heart failure	indication	48447003
Angina pectoris	indication	194828000

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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	DISCN	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	DISCN	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	DISCN	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	DISCN	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	DISCN	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	DISCN	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	DISCN	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	DISCN	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	DISCN	SOLUTION	ORAL	7879842	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	DISCN	TABLET	ORAL	7867996	Dec. 12, 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	DISCN	TABLET	ORAL	7867996	Dec. 12, 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	DISCN	SOLUTION	ORAL	7867996	Dec. 12, 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
5MG/5ML (1MG/ML)	CORLANOR	AMGEN INC	N209964	April 22, 2019	DISCN	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	DISCN	SOLUTION	ORAL	Oct. 22, 2026	PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1	Ion channel	O60741	HCN1_HUMAN	BLOCKER	IC50	5.70	IUPHAR	DRUG LABEL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2	Ion channel	Q9UL51	HCN2_HUMAN	BLOCKER			UNKNOWN	DRUG LABEL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	Ion channel	Q9P1Z3	HCN3_HUMAN	BLOCKER	IC50	5.70	IUPHAR	DRUG LABEL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	Ion channel	Q9Y3Q4	HCN4_HUMAN		EC50	5.37	CHEMBL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1	Ion channel		HCN1_MOUSE		EC50	5.35	CHEMBL
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2	Ion channel		HCN2_MOUSE		EC50	5.34	CHEMBL

External reference:

ID	Source
D07165	KEGG_DRUG
148849-67-6	SECONDARY_CAS_RN
4034416	VANDF
C0257190	UMLSCUI
CHEBI:85969	CHEBI
VNZ	PDB_CHEM_ID
CHEMBL471737	ChEMBL_ID
CHEMBL2145077	ChEMBL_ID
D000077550	MESH_DESCRIPTOR_UI
DB09083	DRUGBANK_ID
2357	IUPHAR_LIGAND_ID
7523	INN_ID
3H48L0LPZQ	UNII
132999	PUBCHEM_CID
1649479	RXNORM
20884	MMSL
233849	MMSL
272983	MMSL
d05706	MMSL
011156	NDDF
011157	NDDF
420906000	SNOMEDCT_US
421228002	SNOMEDCT_US
421692002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	31722-053	TABLET, FILM COATED	5 mg	ORAL	ANDA	27 sections
Ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	31722-054	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	27 sections
Ivabradine	Human Prescription Drug Label	1	46708-679	TABLET, FILM COATED	5 mg	ORAL	ANDA	31 sections
Ivabradine	Human Prescription Drug Label	1	46708-680	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	31 sections
IVABRADINE	HUMAN PRESCRIPTION DRUG LABEL	1	50742-362	TABLET, FILM COATED	5 mg	ORAL	ANDA	24 sections
IVABRADINE	HUMAN PRESCRIPTION DRUG LABEL	1	50742-363	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	24 sections
IVABRADINE	HUMAN PRESCRIPTION DRUG LABEL	1	51407-592	TABLET, FILM COATED	5 mg	ORAL	ANDA	24 sections
IVABRADINE	HUMAN PRESCRIPTION DRUG LABEL	1	51407-593	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	24 sections
Corlanor	HUMAN PRESCRIPTION DRUG LABEL	1	55513-800	TABLET, FILM COATED	5 mg	ORAL	NDA	31 sections
Corlanor	HUMAN PRESCRIPTION DRUG LABEL	1	55513-800	TABLET, FILM COATED	5 mg	ORAL	NDA	31 sections
Corlanor	HUMAN PRESCRIPTION DRUG LABEL	1	55513-810	TABLET, FILM COATED	7.50 mg	ORAL	NDA	31 sections
Corlanor	HUMAN PRESCRIPTION DRUG LABEL	1	55513-810	TABLET, FILM COATED	7.50 mg	ORAL	NDA	31 sections
Corlanor	HUMAN PRESCRIPTION DRUG LABEL	1	55513-813	SOLUTION	5 mg	ORAL	NDA	31 sections
Corlanor	HUMAN PRESCRIPTION DRUG LABEL	1	55513-813	SOLUTION	5 mg	ORAL	NDA	31 sections
Ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	60687-862	TABLET, FILM COATED	5 mg	ORAL	ANDA	27 sections
Ivabradine	Human Prescription Drug Label	1	62332-679	TABLET, FILM COATED	5 mg	ORAL	ANDA	31 sections
Ivabradine	Human Prescription Drug Label	1	62332-680	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	31 sections
ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	69452-190	TABLET, FILM COATED	5 mg	ORAL	ANDA	28 sections
ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	69452-191	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	28 sections
ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	70710-1471	TABLET	5 mg	ORAL	ANDA	26 sections
ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	70710-1472	TABLET	7.50 mg	ORAL	ANDA	26 sections
ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1863	TABLET	5 mg	ORAL	ANDA	2 sections
ivabradine	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1864	TABLET	7.50 mg	ORAL	ANDA	2 sections
Ivabradine	Human Prescription Drug Label	1	72205-336	TABLET, FILM COATED	5 mg	ORAL	ANDA	27 sections
Ivabradine	Human Prescription Drug Label	1	72205-337	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	27 sections
Ivabradine	Human Prescription Drug Label	1	72603-934	TABLET, FILM COATED	5 mg	ORAL	ANDA	27 sections
Ivabradine	Human Prescription Drug Label	1	72603-935	TABLET, FILM COATED	7.50 mg	ORAL	ANDA	27 sections

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ivabradine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Description:

Drug dosage:

ADMET properties:

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Approvals:

FDA Adverse Event Reporting System (Female)

FDA Adverse Event Reporting System (Male)

FDA Adverse Event Reporting System (Geriatric)

FDA Adverse Event Reporting System (Pediatric)

Pharmacologic Action:

Related Drugs by ATC class:

Drug Use | Suggest Off label Use Form| |View source of the data|

🐶 Veterinary Drug Use

🐶 Veterinary products

Acid dissociation constants calculated using MoKa v3.0.0

Orange Book patent data (new drug applications)

Orange Book exclusivity data (new drug applications)

Bioactivity Summary:

External reference:

Pharmaceutical products: