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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

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
Cerebral vasoconstriction	132.80	20.56	31	7128	1002	46677901
Acute pulmonary oedema	130.03	20.56	48	7111	7843	46671060
Hyponatraemia	104.10	20.56	101	7058	101231	46577672
Premature delivery	96.37	20.56	53	7106	22016	46656887
Exposure during pregnancy	93.10	20.56	98	7061	108114	46570789
Posterior reversible encephalopathy syndrome	84.95	20.56	43	7116	15098	46663805
Acute kidney injury	83.70	20.56	138	7021	235717	46443186
Hepatocellular injury	79.63	20.56	52	7107	29470	46649433
Acute motor-sensory axonal neuropathy	74.17	20.56	16	7143	358	46678545
Maternal exposure during pregnancy	64.53	20.56	79	7080	102470	46576433
Cerebral haemorrhage	62.27	20.56	44	7115	28327	46650576
Low birth weight baby	60.91	20.56	25	7134	5409	46673494
Hyperkalaemia	60.53	20.56	55	7104	50654	46628249
Premature labour	54.50	20.56	29	7130	11270	46667633
Bradycardia	53.33	20.56	58	7101	66240	46612663
Haemorrhagic transformation stroke	51.59	20.56	15	7144	1155	46677748
Orthostatic hypotension	51.25	20.56	37	7122	24621	46654282
Cholestasis	50.59	20.56	38	7121	26855	46652048
Eosinophilia	47.33	20.56	32	7127	19185	46659718
Lactic acidosis	46.90	20.56	40	7119	33869	46645034
Fall	45.86	20.56	132	7027	328965	46349938
Haemangioma congenital	43.93	20.56	11	7148	479	46678424
Purpura	43.68	20.56	24	7135	9934	46668969
Acute generalised exanthematous pustulosis	42.17	20.56	23	7136	9382	46669521
Paradoxical drug reaction	41.15	20.56	15	7144	2361	46676542
Hemivertebra	40.30	20.56	8	7151	117	46678786
Thrombocytopenia	39.38	20.56	70	7089	126511	46552392
Caesarean section	39.34	20.56	27	7132	16576	46662327
Drug interaction	39.06	20.56	92	7067	203002	46475901
Fatigue	38.47	20.56	23	7136	608674	46070229
Toxic skin eruption	36.29	20.56	23	7136	12364	46666539
Hypotension	35.98	20.56	97	7062	232492	46446411
Premature baby	34.97	20.56	26	7133	18086	46660817
Hypertension	34.59	20.56	86	7073	196270	46482633
Ischaemic stroke	34.53	20.56	25	7134	16697	46662206
Patent ductus arteriosus	34.09	20.56	15	7144	3847	46675056
Congenital choroid plexus cyst	33.37	20.56	8	7151	290	46678613
Hypokalaemia	33.10	20.56	53	7106	87971	46590932
Haematoma	33.07	20.56	32	7127	31840	46647063
Agranulocytosis	32.37	20.56	27	7132	22158	46656745
Renal failure	31.75	20.56	60	7099	113534	46565369
Pain	31.55	20.56	17	7142	476931	46201972
Gestational hypertension	31.45	20.56	12	7147	2143	46676760
Subarachnoid haemorrhage	30.92	20.56	20	7139	11133	46667770
Arthralgia	30.63	20.56	9	7150	364594	46314309
Foetal growth restriction	29.27	20.56	16	7143	6551	46672352
Tumour rupture	29.05	20.56	6	7153	108	46678795
Anaphylactic shock	28.19	20.56	24	7135	20250	46658653
Foetal arrhythmia	26.80	20.56	6	7153	160	46678743
Metabolic encephalopathy	26.42	20.56	14	7145	5389	46673514
Pre-eclampsia	26.35	20.56	16	7143	7978	46670925
Cutaneous lupus erythematosus	26.19	20.56	11	7148	2518	46676385
Rhabdomyolysis	25.84	20.56	32	7127	41877	46637026
Drug reaction with eosinophilia and systemic symptoms	25.76	20.56	27	7132	29521	46649382
Rash maculo-papular	25.25	20.56	26	7133	27848	46651055
Drug hypersensitivity	24.53	20.56	4	7155	243821	46435082
Acquired haemophilia	24.36	20.56	8	7151	923	46677980
Haemodynamic instability	24.28	20.56	15	7144	7710	46671193
Nausea	24.13	20.56	43	7116	687411	45991492
Cardiogenic shock	24.02	20.56	20	7139	16364	46662539
Mixed liver injury	23.90	20.56	11	7148	3132	46675771
Blood pressure decreased	23.68	20.56	36	7123	57123	46621780
Intra-abdominal haematoma	23.50	20.56	9	7150	1622	46677281
Foetal exposure during pregnancy	23.14	20.56	26	7133	30721	46648182
Wrong patient received product	22.95	20.56	9	7150	1728	46677175
Metabolic acidosis	22.93	20.56	29	7130	38751	46640152
Respiratory distress	22.35	20.56	26	7133	31890	46647013
Rheumatoid arthritis	21.92	20.56	5	7154	240210	46438693
Porphyria acute	21.84	20.56	6	7153	376	46678527
Altered state of consciousness	21.55	20.56	22	7137	23326	46655577
Walking disability	21.29	20.56	8	7151	1370	46677533
Sinus bradycardia	20.57	20.56	17	7142	13765	46665138
Bronchiolitis	20.57	20.56	9	7150	2276	46676627

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
Cerebral vasoconstriction	113.31	19.13	21	4950	191	29947316
Blood lactic acid	78.24	19.13	17	4954	363	29947144
Acute kidney injury	69.69	19.13	145	4826	273697	29673810
Premature baby	64.41	19.13	38	4933	16653	29930854
Foetal disorder	63.93	19.13	16	4955	642	29946865
Cerebral haemorrhage	62.00	19.13	48	4923	32839	29914668
Neutropenia neonatal	56.80	19.13	14	4957	527	29946980
Low birth weight baby	49.98	19.13	23	4948	6053	29941454
Foetal exposure during pregnancy	45.15	19.13	42	4929	36829	29910678
Antiphospholipid antibodies positive	43.25	19.13	10	4961	285	29947222
Cholestasis	33.62	19.13	30	4941	24920	29922587
Haemorrhagic cerebral infarction	33.53	19.13	10	4961	776	29946731
Eosinophilia	32.58	19.13	28	4943	22132	29925375
Phlebitis deep	31.59	19.13	5	4966	15	29947492
Rash maculo-papular	31.19	19.13	29	4942	25389	29922118
Bradycardia	29.90	19.13	45	4926	65481	29882026
Paradoxical drug reaction	28.08	19.13	12	4959	2650	29944857
Brain herniation	27.18	19.13	13	4958	3727	29943780
Extravasation	25.27	19.13	10	4961	1818	29945689
Kidney small	25.20	19.13	5	4966	67	29947440
Cerebral haematoma	24.86	19.13	13	4958	4501	29943006
Hypertension	23.63	19.13	58	4913	121296	29826211
Drug reaction with eosinophilia and systemic symptoms	23.09	19.13	26	4945	28462	29919045
Hyperkalaemia	22.84	19.13	40	4931	65970	29881537
Injection site oedema	22.65	19.13	5	4966	115	29947392
Aortic dissection	22.47	19.13	10	4961	2432	29945075
Renal failure	22.37	19.13	59	4912	128907	29818600
Hypertensive crisis	22.12	19.13	15	4956	8342	29939165
Fatigue	22.06	19.13	13	4958	320660	29626847
Death	21.24	19.13	17	4954	357266	29590241
Phlebitis	21.16	19.13	11	4960	3764	29943743
Respiratory gas exchange disorder	20.78	19.13	6	4965	416	29947091
Cerebral infarction	19.57	19.13	23	4948	26350	29921157
Blood fibrinogen decreased	19.44	19.13	7	4964	982	29946525
Macroglossia	19.44	19.13	5	4966	224	29947283

Pharmacologic Action:

Source	Code	Description
ATC	C08CA04	CARDIOVASCULAR SYSTEM CALCIUM CHANNEL BLOCKERS SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS Dihydropyridine derivatives
FDA CS	M0006414	Dihydropyridines
FDA MoA	N0000000069	Calcium Channel Antagonists
FDA EPC	N0000175421	Dihydropyridine Calcium Channel Blocker
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
FDA MoA	N0000182137	Cytochrome P450 2D6 Inhibitors
FDA MoA	N0000182140	Cytochrome P450 2C19 Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000187062	Cytochrome P450 2C8 Inhibitors

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)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	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
D00617	KEGG_DRUG
54527-84-3	SECONDARY_CAS_RN
4019350	VANDF
4019858	VANDF
C0028005	UMLSCUI
CHEBI:7550	CHEBI
CHEMBL1484	ChEMBL_ID
CHEMBL1200326	ChEMBL_ID
D009529	MESH_DESCRIPTOR_UI
DB00622	DRUGBANK_ID
2559	IUPHAR_LIGAND_ID
4745	INN_ID
CZ5312222S	UNII
4474	PUBCHEM_CID
235230	RXNORM
2278	MMSL
5171	MMSL
d00315	MMSL
000712	NDDF
004518	NDDF
108526002	SNOMEDCT_US
108527006	SNOMEDCT_US
372502001	SNOMEDCT_US

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	26 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9593	INJECTION	2.50 mg	INTRAVENOUS	NDA	26 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9633	INJECTION	0.20 mg	INTRAVENOUS	NDA	27 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9634	INJECTION	0.10 mg	INTRAVENOUS	NDA	27 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9689	INJECTION	25 mg	INTRAVENOUS	NDA	27 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1020	CAPSULE	20 mg	ORAL	ANDA	22 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1430	CAPSULE	30 mg	ORAL	ANDA	22 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0517-0735	INJECTION, SOLUTION	2.50 mg	INTRAVENOUS	ANDA	26 sections
Nicardipine Hydrochloride	Human Prescription Drug Label	1	0781-3204	INJECTION	2.50 mg	INTRAVENOUS	ANDA	12 sections
Nicardipine Hydrochloride	Human Prescription Drug Label	1	0781-9324	INJECTION	2.50 mg	INTRAVENOUS	ANDA	12 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	10122-313	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	23 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	10122-314	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	23 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	10122-325	INJECTION, SOLUTION	0.20 mg	INTRAVENOUS	NDA	23 sections
Nicardipine Hydrochloride	Human Prescription Drug Label	1	14593-124	INJECTION	2.50 mg	INTRAVENOUS	ANDA	12 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	24658-750	CAPSULE	20 mg	ORAL	ANDA	19 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	24658-751	CAPSULE	30 mg	ORAL	ANDA	19 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	40042-047	INJECTION, SOLUTION	2.50 mg	INTRAVENOUS	ANDA	20 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	42806-501	CAPSULE	20 mg	ORAL	ANDA	19 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	42806-502	CAPSULE	30 mg	ORAL	ANDA	19 sections
CARDENE IV	HUMAN PRESCRIPTION DRUG LABEL	1	43066-009	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	24 sections
CARDENE IV	HUMAN PRESCRIPTION DRUG LABEL	1	43066-016	INJECTION, SOLUTION	0.20 mg	INTRAVENOUS	NDA	24 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	43066-021	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	NDA	24 sections
Cardene IV	HUMAN PRESCRIPTION DRUG LABEL	1	43066-024	INJECTION, SOLUTION	0.20 mg	INTRAVENOUS	NDA	24 sections
CARDENE IV	HUMAN PRESCRIPTION DRUG LABEL	1	43066-026	INJECTION, SOLUTION	0.10 mg	INTRAVENTRICULAR	NDA	24 sections
CARDENE IV	HUMAN PRESCRIPTION DRUG LABEL	1	43066-028	INJECTION, SOLUTION	0.20 mg	INTRAVENOUS	NDA	24 sections
nicardipine hydrochloride	Human Prescription Drug Label	1	47335-882	INJECTION	2.50 mg	INTRAVENOUS	NDA	24 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	55150-183	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	24 sections
Nicardipine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	55648-631	INJECTION	2.50 mg	INTRAVENOUS	ANDA	16 sections