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

Stem definition	Drug id	CAS RN
platelet aggregation inhibitors	4184	274693-27-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: ticagrelor brilinta AZD 6140 possia brilique	a cyclopentyltriazolopyrimidine, inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP-receptor indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction Molecular weight: 522.57 Formula: C23H28F2N6O4S CLOGP: 2.55 LIPINSKI: 1 HAC: 10 HDO: 4 TPSA: 138.44 ALOGS: -3.92 ROTB: 10 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

ticagrelor
brilinta
AZD 6140
possia
brilique

a cyclopentyltriazolopyrimidine, inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP-receptor indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction

Molecular weight: 522.57
Formula: C23H28F2N6O4S
CLOGP: 2.55
LIPINSKI: 1
HAC: 10
HDO: 4
TPSA: 138.44
ALOGS: -3.92
ROTB: 10

Status: OFP

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

Drug dosage:

Dose	Unit	Route
0.18	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution)	1.25 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3.38 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.00 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	6.80 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
July 20, 2011	FDA	ASTRAZENECA LP

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
Vascular stent thrombosis	620.58	19.05	116	10824	755	46674367
Thrombosis in device	348.40	19.05	90	10850	2889	46672233
Rhabdomyolysis	320.00	19.05	168	10772	41741	46633381
Acute myocardial infarction	290.21	19.05	144	10796	31780	46643342
Myocardial infarction	266.92	19.05	204	10736	97324	46577798
Dyspnoea	220.72	19.05	414	10526	515134	46159988
Drug interaction	167.33	19.05	221	10719	202873	46472249
Gastrointestinal haemorrhage	158.84	19.05	137	10803	77236	46597886
Haemorrhage	122.47	19.05	102	10838	54767	46620355
Haemorrhage intracranial	108.42	19.05	55	10885	12669	46662453
Acute coronary syndrome	101.47	19.05	49	10891	10155	46664967
Angina pectoris	98.12	19.05	67	10873	26708	46648414
Vascular stent stenosis	85.88	19.05	21	10919	535	46674587
Epistaxis	84.39	19.05	89	10851	64216	46610906
Cerebral haemorrhage	83.22	19.05	62	10878	28309	46646813
Acute kidney injury	82.63	19.05	175	10765	235680	46439442
Chest pain	72.61	19.05	140	10800	176184	46498938
Melaena	71.15	19.05	56	10884	27716	46647406
Angina unstable	65.38	19.05	33	10907	7515	46667607
Atrioventricular block complete	65.05	19.05	33	10907	7594	46667528
Bradycardia	61.96	19.05	77	10863	66221	46608901
Coronary artery thrombosis	57.68	19.05	18	10922	1147	46673975
Sinus arrest	54.51	19.05	19	10921	1712	46673410
Cardiogenic shock	53	19.05	38	10902	16346	46658776
Haematoma	52.62	19.05	50	10890	31822	46643300
Coronary artery stenosis	51.02	19.05	24	10916	4689	46670433
Coronary artery restenosis	50.02	19.05	13	10927	426	46674696
Cardiac failure	49.31	19.05	76	10864	79872	46595250
Anaemia	46.07	19.05	148	10792	255631	46419491
Myopathy	44.31	19.05	27	10913	8854	46666268
Cardiac arrest	39.87	19.05	74	10866	90325	46584797
Platelet function test abnormal	39.71	19.05	8	10932	80	46675042
Intentional product misuse	39.69	19.05	52	10888	47076	46628046
Coronary artery occlusion	38.81	19.05	24	10916	8078	46667044
Rheumatoid arthritis	36.97	19.05	6	10934	240209	46434913
Coronary artery disease	34.43	19.05	41	10899	33711	46641411
Labelled drug-drug interaction medication error	33.94	19.05	23	10917	9038	46666084
Haemorrhagic stroke	33.22	19.05	19	10921	5547	46669575
Upper gastrointestinal haemorrhage	32.97	19.05	29	10911	16709	46658413
Atrioventricular block	32.18	19.05	20	10920	6791	46668331
Coronary artery dissection	31.41	19.05	10	10930	680	46674442
Diabetic macroangiopathy	30.48	19.05	7	10933	135	46674987
Subarachnoid haemorrhage	29.65	19.05	23	10917	11130	46663992
Product name confusion	29.60	19.05	6	10934	62	46675060
Device occlusion	29.47	19.05	18	10922	5927	46669195
Hepatitis	29.40	19.05	37	10903	32178	46642944
Alveolar proteinosis	29.39	19.05	8	10932	314	46674808
Forced vital capacity decreased	28.73	19.05	10	10930	897	46674225
Subdural haematoma	28.61	19.05	24	10916	12973	46662149
Arterial restenosis	28.37	19.05	5	10935	22	46675100
Ventricular asystole	27.93	19.05	6	10934	84	46675038
Eosinophilia	27.70	19.05	28	10912	19189	46655933
Faeces discoloured	27.06	19.05	26	10914	16761	46658361
Acid base balance abnormal	26.01	19.05	7	10933	263	46674859
Coma acidotic	25.55	19.05	6	10934	128	46674994
Brain natriuretic peptide increased	25.43	19.05	15	10925	4635	46670487
Toxicity to various agents	25.33	19.05	9	10931	211757	46463365
Arthralgia	25.25	19.05	29	10911	364574	46310548
Pyrexia	24.97	19.05	27	10913	348775	46326347
Myositis	24.80	19.05	18	10922	7886	46667236
Rectal haemorrhage	24.45	19.05	37	10903	38218	46636904
Spinal cord haemorrhage	23.89	19.05	6	10934	171	46674951
Drug-induced liver injury	22.93	19.05	29	10911	25339	46649783
Hepatitis cholestatic	22.77	19.05	16	10924	6661	46668461
Chest discomfort	22.74	19.05	59	10881	90210	46584912
Infarction	22.72	19.05	11	10929	2290	46672832
Capillary fragility test	21.66	19.05	4	10936	24	46675098
Drug ineffective	21.58	19.05	84	10856	677754	45997368
Iron deficiency anaemia	21.10	19.05	23	10917	17183	46657939
Fibroma	21.05	19.05	8	10932	921	46674201
Myocardial ischaemia	21.03	19.05	20	10920	12729	46662393
Vascular stent occlusion	20.88	19.05	4	10936	30	46675092
Haemoglobin decreased	20.81	19.05	72	10868	128877	46546245
Electrocardiogram ST segment elevation	20.42	19.05	12	10928	3683	46671439
Catheter site haematoma	19.92	19.05	5	10935	142	46674980
Hepatitis acute	19.82	19.05	16	10924	8198	46666924
Cell death	19.80	19.05	10	10930	2278	46672844
Eosinophil cationic protein increased	19.51	19.05	4	10936	44	46675078

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
Vascular stent thrombosis	1238.90	15.77	294	20411	2049	29929724
Thrombosis in device	879.16	15.77	243	20462	3283	29928490
Acute myocardial infarction	432.21	15.77	329	20376	52610	29879163
Dyspnoea	400.36	15.77	773	19932	332522	29599251
Myocardial infarction	300.19	15.77	400	20305	125225	29806548
Gastrointestinal haemorrhage	182.64	15.77	255	20450	83191	29848582
Chest pain	178.09	15.77	303	20402	117324	29814449
Angina pectoris	170.04	15.77	150	20555	29368	29902405
Sinus arrest	159.85	15.77	54	20651	1466	29930307
Rhabdomyolysis	156.82	15.77	206	20499	63374	29868399
Acute coronary syndrome	155.78	15.77	104	20601	13469	29918304
Haemorrhage intracranial	155.47	15.77	108	20597	14924	29916849
Vascular stent stenosis	152.91	15.77	48	20657	1026	29930747
Angina unstable	152.65	15.77	99	20606	12211	29919562
Cerebral haemorrhage	150.50	15.77	147	20558	32740	29899033
Drug interaction	139.33	15.77	375	20330	199193	29732580
Sinoatrial block	130.27	15.77	35	20670	420	29931353
Melaena	124.72	15.77	132	20573	32305	29899468
Coronary artery occlusion	105.71	15.77	76	20629	11081	29920692
Haemorrhage	99.41	15.77	140	20565	45939	29885834
Toxicity to various agents	92.97	15.77	8	20697	177175	29754598
Intentional product misuse	87.96	15.77	114	20591	34553	29897220
Pulmonary haemorrhage	86.74	15.77	63	20642	9329	29922444
Bradycardia	86.26	15.77	159	20546	65367	29866406
Chest discomfort	84.79	15.77	129	20576	45351	29886422
Vascular stent occlusion	81.56	15.77	19	20686	120	29931653
Rectal haemorrhage	78.08	15.77	108	20597	34831	29896942
Coronary artery restenosis	75.32	15.77	29	20676	1154	29930619
Coronary artery stenosis	75.15	15.77	57	20648	9013	29922760
Coronary artery thrombosis	73.73	15.77	34	20671	2130	29929643
Subdural haematoma	70.74	15.77	76	20629	18896	29912877
Anaemia	66.52	15.77	302	20403	207690	29724083
Cardiac ventricular thrombosis	63.39	15.77	23	20682	774	29930999
Atrioventricular block complete	63.10	15.77	50	20655	8427	29923346
Epistaxis	61.61	15.77	122	20583	52859	29878914
Haematuria	60.49	15.77	110	20595	44724	29887049
Subarachnoid haemorrhage	60.41	15.77	52	20653	9834	29921939
Cardiogenic shock	60.16	15.77	66	20639	16795	29914978
Labelled drug-drug interaction medication error	59.52	15.77	53	20652	10485	29921288
Atrioventricular block	58.65	15.77	45	20660	7237	29924536
Coronary artery disease	57.23	15.77	114	20591	49598	29882175
Shock haemorrhagic	56.48	15.77	50	20655	9815	29921958
Febrile neutropenia	55.41	15.77	5	20700	106688	29825085
Device occlusion	54.12	15.77	40	20665	6080	29925693
Platelet aggregation inhibition	54.03	15.77	10	20695	14	29931759
Haemorrhagic stroke	53.97	15.77	40	20665	6107	29925666
Brain herniation	53.65	15.77	33	20672	3707	29928066
Cardiac arrest	53.34	15.77	163	20542	92687	29839086
Pyrexia	49.22	15.77	80	20625	294409	29637364
Completed suicide	45.87	15.77	7	20698	99485	29832288
Haematoma	44.68	15.77	68	20637	23885	29907888
Gastric haemorrhage	44.53	15.77	43	20662	9424	29922349
White blood cell count decreased	43.40	15.77	4	20701	83943	29847830
Pneumonia	42.86	15.77	106	20599	334200	29597573
Blood loss anaemia	42.35	15.77	38	20667	7589	29924184
Product dose omission issue	41.98	15.77	149	20556	91482	29840291
Arterial restenosis	41.43	15.77	10	20695	75	29931698
Gastric ulcer haemorrhage	40.96	15.77	32	20673	5282	29926491
Neutropenia	40.66	15.77	19	20686	128521	29803252
Thrombosis	40.61	15.77	90	20615	42141	29889632
Ventricular asystole	39.58	15.77	11	20694	151	29931622
Rash maculo-papular	38.97	15.77	66	20639	25352	29906421
Sinus bradycardia	38.66	15.77	44	20661	11651	29920122
Haematemesis	36.22	15.77	65	20640	26138	29905635
Malignant neoplasm progression	35.92	15.77	4	20701	72283	29859490
Diarrhoea	34.71	15.77	117	20588	333986	29597787
Haemoptysis	34.23	15.77	70	20635	31008	29900765
Therapy cessation	34.10	15.77	47	20658	15090	29916683
Muscle enzyme increased	31.75	15.77	10	20695	216	29931557
Base excess decreased	31.62	15.77	10	20695	219	29931554
Sepsis	31.33	15.77	33	20672	146362	29785411
Cheyne-Stokes respiration	31.28	15.77	10	20695	227	29931546
Ventricular fibrillation	31.13	15.77	45	20660	15093	29916680
Upper gastrointestinal haemorrhage	30.90	15.77	55	20650	21973	29909800
Constipation	30.90	15.77	20	20685	112886	29818887
Pericardial haemorrhage	30.23	15.77	21	20684	2897	29928876
Arterial thrombosis	29.80	15.77	16	20689	1390	29930383
Oxygen consumption decreased	29.71	15.77	9	20696	170	29931603
Decreased appetite	29.68	15.77	36	20669	149874	29781899
Mixed liver injury	29.64	15.77	18	20687	1975	29929798
Drug abuse	29.43	15.77	10	20695	82062	29849711
Troponin increased	28.73	15.77	33	20672	8824	29922949
Intrapericardial thrombosis	28.39	15.77	7	20698	58	29931715
Iron deficiency anaemia	28.23	15.77	33	20672	8991	29922782
Cardiac tamponade	27.50	15.77	24	20681	4620	29927153
Mallory-Weiss syndrome	27.33	15.77	15	20690	1361	29930412
Disease progression	26.52	15.77	11	20694	79863	29851910
Plasma cell myeloma	26.45	15.77	3	20702	53459	29878314
Dehydration	26.25	15.77	28	20677	123511	29808262
Brain natriuretic peptide increased	26.23	15.77	22	20683	4013	29927760
Retroperitoneal haematoma	25.71	15.77	18	20687	2514	29929259
Coronary artery dissection	25.52	15.77	8	20697	170	29931603
Haemoglobin decreased	25.42	15.77	150	20555	113948	29817825
Oedema peripheral	24.79	15.77	22	20683	105810	29825963
Anterior interosseous syndrome	24.47	15.77	5	20700	15	29931758
Atrioventricular block second degree	24.40	15.77	19	20686	3121	29928652
Orthopnoea	23.99	15.77	22	20683	4518	29927255
Nasopharyngitis	23.23	15.77	6	20699	58843	29872930
Sinus node dysfunction	23.04	15.77	20	20685	3823	29927950
Overdose	22.98	15.77	15	20690	84322	29847451
Circumstance or information capable of leading to medication error	22.49	15.77	14	20691	1605	29930168
Faeces discoloured	22.42	15.77	37	20668	13909	29917864
Left ventricular enlargement	22.41	15.77	10	20695	580	29931193
Ischaemic stroke	22.01	15.77	40	20665	16235	29915538
Stent placement	21.85	15.77	21	20684	4575	29927198
Hepatitis cholestatic	21.70	15.77	27	20678	7845	29923928
Gout	21.47	15.77	41	20664	17274	29914499
Seizure	21.27	15.77	22	20683	98453	29833320
Reperfusion injury	21.16	15.77	6	20699	89	29931684
Sleep apnoea syndrome	21.01	15.77	40	20665	16817	29914956
Pancytopenia	20.74	15.77	17	20688	85035	29846738
Hypertrophy	20.57	15.77	8	20697	327	29931446
Cerebral haematoma	20.28	15.77	20	20685	4494	29927279
Gastritis erosive	20.06	15.77	22	20683	5591	29926182
Post procedural haemorrhage	20.02	15.77	26	20679	7884	29923889
Walking disability	20.00	15.77	10	20695	749	29931024
Hepatocellular injury	19.82	15.77	50	20655	25421	29906352
Suffocation feeling	19.66	15.77	9	20696	554	29931219
Asphyxia	18.94	15.77	21	20684	5404	29926369
Microcytic anaemia	18.73	15.77	14	20691	2164	29929609
Bladder tamponade	18.62	15.77	8	20697	423	29931350
Hyperlipidaemia	18.58	15.77	34	20671	13873	29917900
Duodenal ulcer	18.30	15.77	28	20677	9873	29921900
Mean cell haemoglobin decreased	18.29	15.77	11	20694	1186	29930587
Weight increased	18.23	15.77	15	20690	74898	29856875
Platelet aggregation decreased	18.13	15.77	4	20701	19	29931754
Myelofibrosis	17.92	15.77	12	20693	1559	29930214
Myocardial ischaemia	17.88	15.77	38	20667	17279	29914494
Platelet aggregation abnormal	17.80	15.77	4	20701	21	29931752
Confusional state	17.79	15.77	42	20663	134792	29796981
Calculus urinary	17.68	15.77	11	20694	1260	29930513
Electrocardiogram abnormal	17.52	15.77	21	20684	5871	29925902
Urinary bladder haemorrhage	17.38	15.77	12	20693	1639	29930134
Neuropathy peripheral	17.29	15.77	14	20691	70461	29861312
Intracardiac thrombus	17.28	15.77	14	20691	2434	29929339
Pulmonary alveolar haemorrhage	17.23	15.77	22	20683	6559	29925214
Autoimmune myositis	17.07	15.77	4	20701	26	29931747
Electrocardiogram ST segment elevation	16.91	15.77	18	20687	4424	29927349
Muscle necrosis	16.83	15.77	9	20696	775	29930998
Cerebellar haemorrhage	16.68	15.77	11	20694	1393	29930380
Ventricular tachycardia	16.68	15.77	45	20660	23817	29907956
Gastric ulcer	16.57	15.77	34	20671	15087	29916686
Product administration error	16.56	15.77	33	20672	14344	29917429
Computerised tomogram head abnormal	16.46	15.77	4	20701	31	29931742
Diverticulitis intestinal haemorrhagic	16.44	15.77	7	20698	362	29931411
Back pain	16.03	15.77	29	20676	102567	29829206

Pharmacologic Action:

Source	Code	Description
ATC	B01AC24	BLOOD AND BLOOD FORMING ORGANS ANTITHROMBOTIC AGENTS ANTITHROMBOTIC AGENTS Platelet aggregation inhibitors excl. heparin
FDA PE	N0000008832	Decreased Platelet Aggregation
MeSH PA	D006401	Hematologic Agents
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D010975	Platelet Aggregation Inhibitors
MeSH PA	D058914	Purinergic Antagonists
MeSH PA	D058919	Purinergic P2 Receptor Antagonists
MeSH PA	D058921	Purinergic P2Y Receptor Antagonists
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA EPC	N0000182142	P2Y12 Platelet Inhibitor
FDA MoA	N0000182143	P2Y12 Receptor Antagonists
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190115	Cytochrome P450 3A5 Inhibitors
FDA MoA	N0000190482	Phenylalanine Hydroxylase Activators
CHEBI has role	CHEBI:50427	platelet aggregation inhibitors
CHEBI has role	CHEBI:68563	purinergic receptor subtype p2y12 antagonist

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Acute coronary syndrome	indication	394659003
Peripheral vascular disease	indication	400047006
Percutaneous coronary intervention	indication	415070008
Myocardial Reinfarction Prevention	indication
Intracranial hemorrhage	contraindication	1386000
Hepatic failure	contraindication	59927004
Disease of liver	contraindication	235856003	DOID:409
Surgical procedure	contraindication	387713003
Significant Bleeding	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.07	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
60MG	BRILINTA	ASTRAZENECA	N022433	Sept. 3, 2015	RX	TABLET	ORAL	May 28, 2023	TO REDUCE THE RISK OF A FIRST MYOCARDIAL INFARCTION (MI) OR STROKE IN PATIENTS WITH CORONULLRY ARTERY DISEASE (CAD) AT HIGH RISK FOR SUCH EVENTS
90MG	BRILINTA	ASTRAZENECA	N022433	July 20, 2011	RX	TABLET	ORAL	May 28, 2023	TO REDUCE THE RISK OF A FIRST MYOCARDIAL INFARCTION (MI) OR STROKE IN PATIENTS WITH CORONULLRY ARTERY DISEASE (CAD) AT HIGH RISK FOR SUCH EVENTS
60MG	BRILINTA	ASTRAZENECA	N022433	Sept. 3, 2015	RX	TABLET	ORAL	Nov. 5, 2023	REDUCE THE RISK OF STROKE IN PATIENTS WITH ACUTE ISCHEMIC STROKE (NIH STROKE SCALE SCORE <=5) OR HIGH-RISK TRANSIENT ISCHEMIC ATTACK (TIA)
90MG	BRILINTA	ASTRAZENECA	N022433	July 20, 2011	RX	TABLET	ORAL	Nov. 5, 2023	REDUCE THE RISK OF STROKE IN PATIENTS WITH ACUTE ISCHEMIC STROKE (NIH STROKE SCALE SCORE <=5) OR HIGH-RISK TRANSIENT ISCHEMIC ATTACK (TIA)

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
P2Y purinoceptor 12	GPCR	Q9H244	P2Y12_HUMAN	NEGATIVE ALLOSTERIC MODULATOR	Ki	7.85	CHEMBL	CHEMBL
Equilibrative nucleoside transporter 1	Transporter	Q99808	S29A1_HUMAN	INHIBITOR	Ki	7.30	IUPHAR
P2Y purinoceptor 12	Unclassified		P2Y12_RAT		IC50	5.38	CHEMBL

External reference:

ID	Source
4030908	VUID
N0000182973	NUI
D09017	KEGG_DRUG
4030908	VANDF
C1608718	UMLSCUI
CHEBI:68558	CHEBI
TIQ	PDB_CHEM_ID
CHEMBL398435	ChEMBL_ID
D000077486	MESH_DESCRIPTOR_UI
9871419	PUBCHEM_CID
8772	INN_ID
DB08816	DRUGBANK_ID
GLH0314RVC	UNII
1765	IUPHAR_LIGAND_ID
1116632	RXNORM
182026	MMSL
235692	MMSL
27677	MMSL
d07721	MMSL
013611	NDDF
698805004	SNOMEDCT_US
704464003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
BRILINTA	HUMAN PRESCRIPTION DRUG LABEL	1	0186-0776	TABLET	60 mg	ORAL	NDA	31 sections
BRILINTA	HUMAN PRESCRIPTION DRUG LABEL	1	0186-0777	TABLET	90 mg	ORAL	NDA	31 sections
BRILINTA	HUMAN PRESCRIPTION DRUG LABEL	1	55154-9618	TABLET	90 mg	ORAL	NDA	28 sections
ticagrelor	HUMAN PRESCRIPTION DRUG LABEL	1	69238-1134	TABLET	90 mg	ORAL	ANDA	28 sections