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

Stem definition	Drug id	CAS RN
fibrinogen receptor antagonists (glycoprotein IIb/IIIa receptor antagonists)	2680	144494-65-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: tirofiban aggrestat tirofiban hydrochloride tirofiban HCl tirofiban hydrochloride monohydrate L-700,462 aggrastat	a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation, when administered intravenously inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner Molecular weight: 440.60 Formula: C22H36N2O5S CLOGP: 2 LIPINSKI: 0 HAC: 7 HDO: 3 TPSA: 104.73 ALOGS: -5.14 ROTB: 13 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

tirofiban
aggrestat
tirofiban hydrochloride
tirofiban HCl
tirofiban hydrochloride monohydrate
L-700,462
aggrastat

a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation, when administered intravenously inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner

Molecular weight: 440.60
Formula: C22H36N2O5S
CLOGP: 2
LIPINSKI: 0
HAC: 7
HDO: 3
TPSA: 104.73
ALOGS: -5.14
ROTB: 13

Status: OFP

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

Drug dosage:

Dose	Unit	Route
10	mg	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	65 %	Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability)	0 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.34 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.36 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1.60 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
May 14, 1998	FDA	MEDICURE

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
Thrombocytopenia	104.85	88.24	41	442	138686	53209897

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
Thrombocytopenia	245.23	54.33	108	880	148191	32364347
Cerebral haemorrhage	65.21	54.33	28	960	34719	32477819
Cardiogenic shock	64.35	54.33	24	964	20638	32491900
Vascular stent thrombosis	58.95	54.33	14	974	2533	32510005

Pharmacologic Action:

Source	Code	Description
ATC	B01AC17	BLOOD AND BLOOD FORMING ORGANS ANTITHROMBOTIC AGENTS ANTITHROMBOTIC AGENTS Platelet aggregation inhibitors excl. heparin
FDA PE	N0000008832	Decreased Platelet Aggregation
FDA EPC	N0000175578	Platelet Aggregation Inhibitor
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D005343	Fibrinolytic Agents
MeSH PA	D006401	Hematologic Agents
MeSH PA	D010975	Platelet Aggregation Inhibitors
CHEBI has role	CHEBI:48676	fibrin modulating agents
CHEBI has role	CHEBI:50249	anticoagulante
CHEBI has role	CHEBI:50433	platelet glycoprotein-IIb/IIIa receptor antagonists

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Non-Q wave myocardial infarction	indication	314207007
Acute coronary syndrome	indication	394659003
Percutaneous coronary intervention	indication	415070008
Intracranial hemorrhage	contraindication	1386000
Acute pericarditis	contraindication	15555002
Arteriovenous malformation	contraindication	24551003
Acute nephropathy	contraindication	58574008
Blood coagulation disorder	contraindication	64779008	DOID:1247
Neoplasm of brain	contraindication	126952004	DOID:1319
Bleeding	contraindication	131148009
Lithotripsy	contraindication	133864008
Cerebrovascular accident	contraindication	230690007
Arterial aneurysm	contraindication	233981004
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Dissection of aorta	contraindication	308546005
Surgical procedure	contraindication	387713003
Traumatic injury	contraindication	417746004
Hypertensive urgency	contraindication	443482000
Hemorrhagic Diabetic Retinopathy	contraindication
Hemodialysis with High-Flux Membrane	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.02	acidic
pKa2	13.5	acidic
pKa3	10.31	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 12.5MG BASE/50ML (EQ 0.25MG BASE/ML)	AGGRASTAT	MEDICURE	N020912	May 14, 1998	DISCN	INJECTABLE	INJECTION	6770660	May 1, 2023	A DOSING REGIMEN OF AGGRASTAT (TIROFIBAN HYDROCHLORIDE)(25MCG/KG FOLLOWED BY 0.15MCG/KG/MIN INFUSION) TO REDUCE THE RATE OF THROMBOTIC CORONARY EVENTS ASSOCIATED WITH ACUTE CORONARY SYNDROME (ACS) IN PATIENTS WITH NON-ST ELEVATION ACS
EQ 3.75MG BASE/15ML (EQ 0.25MG BASE/ML)	AGGRASTAT	MEDICURE	N020912	Aug. 31, 2016	RX	SOLUTION	INJECTION	6770660	May 1, 2023	A DOSING REGIMEN OF AGGRASTAT (TIROFIBAN HYDROCHLORIDE)(25MCG/KG FOLLOWED BY 0.15MCG/KG/MIN INFUSION) TO REDUCE THE RATE OF THROMBOTIC CORONARY EVENTS ASSOCIATED WITH ACUTE CORONARY SYNDROME (ACS) IN PATIENTS WITH NON-ST ELEVATION ACS
EQ 12.5MG BASE/250ML (EQ 0.05MG BASE/ML)	AGGRASTAT	MEDICURE	N020913	April 20, 2000	RX	SOLUTION	INTRAVENOUS	6770660	May 1, 2023	A DOSING REGIMEN OF AGGRASTAT (TIROFIBAN HYDROCHLORIDE)(25MCG/KG FOLLOWED BY 0.15MCG/KG/MIN INFUSION) TO REDUCE THE RATE OF THROMBOTIC CORONARY EVENTS ASSOCIATED WITH ACUTE CORONARY SYNDROME (ACS) IN PATIENTS WITH NON-ST ELEVATION ACS
EQ 25MG BASE/500ML (EQ 0.05MG BASE/ML)	AGGRASTAT	MEDICURE	N020913	May 14, 1998	DISCN	SOLUTION	INTRAVENOUS	6770660	May 1, 2023	A DOSING REGIMEN OF AGGRASTAT (TIROFIBAN HYDROCHLORIDE)(25MCG/KG FOLLOWED BY 0.15MCG/KG/MIN INFUSION) TO REDUCE THE RATE OF THROMBOTIC CORONARY EVENTS ASSOCIATED WITH ACUTE CORONARY SYNDROME (ACS) IN PATIENTS WITH NON-ST ELEVATION ACS
EQ 5MG BASE/100ML (EQ 0.05MG BASE/ML)	AGGRASTAT	MEDICURE	N020913	May 17, 2002	RX	SOLUTION	INTRAVENOUS	6770660	May 1, 2023	A DOSING REGIMEN OF AGGRASTAT (TIROFIBAN HYDROCHLORIDE)(25MCG/KG FOLLOWED BY 0.15MCG/KG/MIN INFUSION) TO REDUCE THE RATE OF THROMBOTIC CORONARY EVENTS ASSOCIATED WITH ACUTE CORONARY SYNDROME (ACS) IN PATIENTS WITH NON-ST ELEVATION ACS

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Integrin alpha-IIb/beta-3	Adhesion	P05106 P08514	ITB3_HUMAN ITA2B_HUMAN	INHIBITOR	IC50	7.96		SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
4024116	VUID
N0000022121	NUI
D01029	KEGG_DRUG
150915-40-5	SECONDARY_CAS_RN
4021109	VANDF
4024116	VANDF
C0247025	UMLSCUI
CHEBI:9605	CHEBI
AGG	PDB_CHEM_ID
CHEMBL916	ChEMBL_ID
CHEMBL3189072	ChEMBL_ID
CHEMBL1704	ChEMBL_ID
D000077466	MESH_DESCRIPTOR_UI
DB00775	DRUGBANK_ID
6586	IUPHAR_LIGAND_ID
7345	INN_ID
GGX234SI5H	UNII
60947	PUBCHEM_CID
187024	RXNORM
11701	MMSL
5588	MMSL
d04315	MMSL
007531	NDDF
108981004	SNOMEDCT_US
386953003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
AGGRASTAT	HUMAN PRESCRIPTION DRUG LABEL	1	25208-001	INJECTION, SOLUTION	3.75 mg	INTRAVENOUS	NDA	25 sections
AGGRASTAT	HUMAN PRESCRIPTION DRUG LABEL	1	25208-002	INJECTION, SOLUTION	5 mg	INTRAVENOUS	NDA	25 sections
Tirofiban hydrochloride	Human Prescription Drug Label	1	68083-145	INJECTION, SOLUTION	12.50 mg	INTRAVENOUS	ANDA	25 sections