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

Stem definition	Drug id	CAS RN
calcium channel blockers, nifedipine derivatives	1909	55985-32-5

Description:

Molecule

Description

Molfile Inchi Smiles Synonyms: nicardipine (+/-)-Nicardipine perpidine nicardipine hydrochloride nicardipine HCl

A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. Molecular weight: 479.53 Formula: C26H29N3O6 CLOGP: 5.23 LIPINSKI: 1 HAC: 9 HDO: 1 TPSA: 111.01 ALOGS: -5.29 ROTB: 11 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

Dose	Unit	Route
90	mg	O
90	mg	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	7.90 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	4.17 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	23 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	1 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	11 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.01 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	4.10 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Dec. 21, 1988	FDA	CHIESI USA INC

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
Acute pulmonary oedema	250.66	70.92	39	295	1224	2356527
Exposure during pregnancy	239.31	70.92	61	273	25158	2332593
Maternal exposure during pregnancy	190.59	70.92	46	288	14817	2342934
Premature delivery	169.27	70.92	32	302	3168	2354583

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
Premature baby	131.80	99.31	26	199	2916	1743640
Foetal disorder	130.81	99.31	16	209	63	1746493
Foetal exposure during pregnancy	111.83	99.31	26	199	6333	1740223
Neutropenia neonatal	110.24	99.31	13	212	34	1746522
Low birth weight baby	105.85	99.31	18	207	869	1745687

Pharmacologic Action:

Source	Code	Description
ATC	C08CA04	CARDIOVASCULAR SYSTEM CALCIUM CHANNEL BLOCKERS SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS Dihydropyridine derivatives
FDA MoA	N0000000069	Calcium Channel Antagonists
FDA EPC	N0000175421	Dihydropyridine Calcium Channel Blocker
FDA CS	M0006414	Dihydropyridines
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000182137	Cytochrome P450 2D6 Inhibitors
FDA MoA	N0000187062	Cytochrome P450 2C8 Inhibitors
FDA MoA	N0000182140	Cytochrome P450 2C19 Inhibitors
MeSH PA	D000959	Antihypertensive Agents
MeSH PA	D002121	Calcium Channel Blockers
MeSH PA	D000077264	Calcium-Regulating Hormones and Agents
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D049990	Membrane Transport Modulators
MeSH PA	D014665	Vasodilator Agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Hypertensive disorder	indication	38341003	DOID:10763
Angina pectoris	indication	194828000
Prinzmetal angina	off-label use	87343002
Raynaud's phenomenon	off-label use	266261006
Portal hypertension	contraindication	34742003	DOID:10762
Low blood pressure	contraindication	45007003
Chronic heart failure	contraindication	48447003
Chronic idiopathic constipation	contraindication	82934008
Impaired renal function disorder	contraindication	197663003
Disease of liver	contraindication	235856003	DOID:409
Cerebral hemorrhage	contraindication	274100004
Cerebral infarction	contraindication	432504007	DOID:3526
Severe Aortic Valve Stenosis	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	7.02	Basic
pKa2	2.37	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
20MG/200ML (0.1MG/ML)	CARDENE IN 0.86% SODIUM CHLORIDE IN PLASTIC CONTAINER	CHIESI	N019734	July 31, 2008	RX	INJECTABLE	INTRAVENOUS	7659291	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
20MG/200ML (0.1MG/ML)	CARDENE IN 4.8% DEXTROSE IN PLASTIC CONTAINER	CHIESI	N019734	July 31, 2008	RX	INJECTABLE	INTRAVENOUS	7659291	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
20MG/200ML (0.1MG/ML)	CARDENE IN 0.86% SODIUM CHLORIDE IN PLASTIC CONTAINER	CHIESI	N019734	July 31, 2008	RX	INJECTABLE	INTRAVENOUS	8455524	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
20MG/200ML (0.1MG/ML)	CARDENE IN 4.8% DEXTROSE IN PLASTIC CONTAINER	CHIESI	N019734	July 31, 2008	RX	INJECTABLE	INTRAVENOUS	8455524	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
40MG/200ML (0.2MG/ML)	CARDENE IN 0.83% SODIUM CHLORIDE IN PLASTIC CONTAINER	CHIESI	N019734	Nov. 7, 2008	RX	INJECTABLE	INTRAVENOUS	7659291	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
40MG/200ML (0.2MG/ML)	CARDENE IN 5.0% DEXTROSE IN PLASTIC CONTAINER	CHIESI	N019734	Nov. 7, 2008	DISCN	INJECTABLE	INTRAVENOUS	7659291	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
40MG/200ML (0.2MG/ML)	CARDENE IN 0.83% SODIUM CHLORIDE IN PLASTIC CONTAINER	CHIESI	N019734	Nov. 7, 2008	RX	INJECTABLE	INTRAVENOUS	8455524	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF
40MG/200ML (0.2MG/ML)	CARDENE IN 5.0% DEXTROSE IN PLASTIC CONTAINER	CHIESI	N019734	Nov. 7, 2008	DISCN	INJECTABLE	INTRAVENOUS	8455524	April 18, 2027	METHOD FOR TREATING ACUTE ELEVATIONS OF BLOOD PRESSURE IN HUMAN SUBJECT IN NEED THEREOF

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
Voltage-gated L-type calcium channel	Ion channel	Q01668 Q13936	CAC1C_HUMAN CAC1D_HUMAN	BLOCKER				CHEMBL	CHEMBL
Nuclear receptor subfamily 1 group I member 2	Nuclear hormone receptor	O75469	NR1I2_HUMAN					WOMBAT-PK
Cytochrome P450 2C9	Enzyme	P11712	CP2C9_HUMAN		IC50	6.55		WOMBAT-PK
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	6.38		WOMBAT-PK
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	5.32		CHEMBL
Malate dehydrogenase cytoplasmic	Enzyme	P40925	MDHC_HUMAN		IC50	4.30		CHEMBL
Adenosine receptor A3	GPCR	P0DMS8	AA3R_HUMAN		Ki	5.49		CHEMBL
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		IC50	4.78		CHEMBL
Voltage-dependent T-type calcium channel subunit alpha-1H	Ion channel	O95180	CAC1H_HUMAN		Ki	5.55		WOMBAT-PK
Adrenergic receptor alpha-2	GPCR		ADA2A_RAT ADA2B_RAT ADA2C_RAT		IC50	5.85		CHEMBL
Equilibrative nucleoside transporter 1	Transporter		S29A1_RAT		Ki	5.27		CHEMBL
Beta-lactamase	Enzyme		AMPC_ECOLI		IC50	4.70		CHEMBL
Adenosine receptor A3	GPCR		AA3R_RAT		Ki	4.96		CHEMBL
Adrenergic receptor alpha-1	GPCR		ADA1A_RAT ADA1B_RAT ADA1D_RAT		IC50	5.44		CHEMBL
Adenosine receptor A2a	GPCR		AA2AR_RAT		Ki	4.20		CHEMBL
Voltage-gated L-type calcium channel	Ion channel		CAC1C_RAT CAC1D_RAT CAC1S_RAT		Ki	9.08		CHEMBL
Adenosine receptor A1	GPCR		AA1R_RAT		Ki	4.71		CHEMBL
Potassium voltage-gated channel subfamily A member 4	Unclassified		KCNA4_RAT	BLOCKER	IC50	6.10		IUPHAR

External reference:

ID	Source
4019858	VUID
N0000147944	NUI
C0028005	UMLSCUI
D00617	KEGG_DRUG
108526002	SNOMEDCT_US
7396	RXNORM
372502001	SNOMEDCT_US
d00315	MMSL
4019858	VANDF
004518	NDDF
CZ5312222S	UNII
4745	INN_ID
CHEMBL1484	ChEMBL_ID
DB00622	DRUGBANK_ID
CHEMBL1200326	ChEMBL_ID
54527-84-3	SECONDARY_CAS_RN
CHEBI:7550	CHEBI
D009529	MESH_DESCRIPTOR_UI
4474	PUBCHEM_CID
2559	IUPHAR_LIGAND_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9542	INJECTION	2.50 mg	INTRAVENOUS	NDA	17 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9593	INJECTION	2.50 mg	INTRAVENOUS	NDA	17 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9633	INJECTION	0.20 mg	INTRAVENOUS	NDA	17 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9634	INJECTION	0.10 mg	INTRAVENOUS	NDA	17 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9689	INJECTION	25 mg	INTRAVENOUS	NDA	17 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1020	CAPSULE	20 mg	ORAL	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1430	CAPSULE	30 mg	ORAL	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3204	INJECTION	2.50 mg	INTRAVENOUS	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0781-9324	INJECTION	2.50 mg	INTRAVENOUS	ANDA	11 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	10122-313	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	15 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	10122-314	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	15 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	10122-325	INJECTION, SOLUTION	0.20 mg	INTRAVENOUS	NDA	15 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	14593-124	INJECTION	2.50 mg	INTRAVENOUS	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	24658-750	CAPSULE	20 mg	ORAL	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	24658-751	CAPSULE	30 mg	ORAL	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	40042-047	INJECTION, SOLUTION	2.50 mg	INTRAVENOUS	ANDA	12 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	42806-501	CAPSULE	20 mg	ORAL	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	42806-502	CAPSULE	30 mg	ORAL	ANDA	11 sections
NICARDIPINE HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	51662-1428	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	17 sections
NICARDIPINE HYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	51662-1482	INJECTION	25 mg	INTRAVENOUS	NDA	17 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	55648-631	INJECTION	2.50 mg	INTRAVENOUS	ANDA	12 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	64679-631	INJECTION	2.50 mg	INTRAVENOUS	ANDA	13 sections
Cardene	HUMAN PRESCRIPTION DRUG LABEL	1	68151-0089	CAPSULE, EXTENDED RELEASE	30 mg	ORAL	NDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	68151-0092	CAPSULE	20 mg	ORAL	ANDA	11 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	68151-0093	CAPSULE	30 mg	ORAL	ANDA	11 sections