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Details

Stereochemistry RACEMIC
Molecular Formula 2C24H26N2O4.H2O.2H3O4P
Molecular Weight 1026.956
Optical Activity ( + / - )
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARVEDILOL PHOSPHATE

SMILES

COc1ccccc1OCCNCC(COc2cccc3c2c4ccccc4[nH]3)O.COc1ccccc1OCCNCC(COc2cccc3c2c4ccccc4[nH]3)O.OP(=O)(O)O.OP(=O)(O)O.O

InChI

InChIKey=LHNYXTULDSJZRB-UHFFFAOYSA-N
InChI=1S/2C24H26N2O4.2H3O4P.H2O/c2*1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20;2*1-5(2,3)4;/h2*2-12,17,25-27H,13-16H2,1H3;2*(H3,1,2,3,4);1H2

HIDE SMILES / InChI

Molecular Formula C24H26N2O4
Molecular Weight 406.4751
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula H3O4P
Molecular Weight 97.9952
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Carvedilol competitively blocks β1, β2 and α1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through α1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. COREG® (carvedilol) is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol is the first drug of its kind to be approved for the treatment of congestive heart failure, and is now the standard of care for this devastating disease. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.

Originator

Curator's Comment:: reference retrieved from http://www.drugfuture.com/chemdata/carvedilol.html

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COREG

Approved Use

COREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization. COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure). COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

8.1103677E11
Primary
COREG

Approved Use

COREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization. COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure). COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

8.1103677E11
Primary
COREG

Approved Use

COREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization. COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure). COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

8.1103677E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
18.4 ng/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (+)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
8.46 ng/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (-)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
26.5 ng/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
94.3 ng × h/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (+)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
42.2 ng × h/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (-)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
139 ng × h/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Co-administed with::
lorazepam(7 mg)
Sources:
unknown, 41 years
n = 1
Health Status: unknown
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Other AEs: Wheezing...
Other AEs:
Wheezing (1 patient)
Sources:
80 mg 1 times / day multiple, oral
Highest studied dose
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, 66.7±12.0 years
n = 7
Health Status: unhealthy
Condition: chronic heart failure
Age Group: 66.7±12.0 years
Sex: M+F
Population Size: 7
Sources:
375 mg single, oral
Overdose
Dose: 375 mg
Route: oral
Route: single
Dose: 375 mg
Co-administed with::
simvastatin(fifteen 20-mg tablets)
Sources:
unhealthy, 84 years
n = 1
Health Status: unhealthy
Age Group: 84 years
Sex: M
Population Size: 1
Sources:
Other AEs: Hypotension...
Other AEs:
Hypotension (1 patient)
Sources:
50 mg 1 times / day steady, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
n = 765
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Population Size: 765
Sources:
Disc. AE: Hypotension...
AEs leading to
discontinuation/dose reduction:
Hypotension (0.7%)
Sources:
20 mg 2 times / day multiple, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Disc. AE: Congestive cardiac failure...
AEs leading to
discontinuation/dose reduction:
Congestive cardiac failure (moderate, 1 patient)
Sources: Page: p. 61
25 mg 2 times / day steady, oral
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, adult
n = 1156
Health Status: unhealthy
Condition: severe heart failure
Age Group: adult
Population Size: 1156
Sources:
Disc. AE: Dizziness...
AEs leading to
discontinuation/dose reduction:
Dizziness (1.3%)
Sources:
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Disc. AE: Abdominal distension...
AEs leading to
discontinuation/dose reduction:
Abdominal distension (1 patient)
Sources: Page: p. 61
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (moderate, 1 patient)
Sources: Page: p. 61
AEs

AEs

AESignificanceDosePopulation
Wheezing 1 patient
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Co-administed with::
lorazepam(7 mg)
Sources:
unknown, 41 years
n = 1
Health Status: unknown
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Hypotension 1 patient
375 mg single, oral
Overdose
Dose: 375 mg
Route: oral
Route: single
Dose: 375 mg
Co-administed with::
simvastatin(fifteen 20-mg tablets)
Sources:
unhealthy, 84 years
n = 1
Health Status: unhealthy
Age Group: 84 years
Sex: M
Population Size: 1
Sources:
Hypotension 0.7%
Disc. AE
50 mg 1 times / day steady, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
n = 765
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Population Size: 765
Sources:
Congestive cardiac failure moderate, 1 patient
Disc. AE
20 mg 2 times / day multiple, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Dizziness 1.3%
Disc. AE
25 mg 2 times / day steady, oral
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, adult
n = 1156
Health Status: unhealthy
Condition: severe heart failure
Age Group: adult
Population Size: 1156
Sources:
Abdominal distension 1 patient
Disc. AE
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Rash moderate, 1 patient
Disc. AE
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
PubMed

PubMed

TitleDatePubMed
Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart.
2000
[Clinical efficacy of carvedilol in patients with severe cardiac insufficiency].
2001
CAPRICORN: a story of alpha allocation and beta-blockers in left ventricular dysfunction post-MI.
2001 Apr
Carvedilol--a new dimension in pediatric heart failure therapy.
2001 Apr
50th Annual scientific sessions of the American college of cardiology.
2001 Apr 10
Development of a capillary electrophoresis assay for the determination of carvedilol enantiomers in serum using cyclodextrins.
2001 Feb
Variceal bleeding and portal hypertension: still a therapeutic challenge?
2001 Feb
[Economic study of carvedilol in heart failure. A cost effectiveness study in France].
2001 Feb
Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial.
2001 Feb
Detection of low levels of the amorphous phase in crystalline pharmaceutical materials by thermally stimulated current spectrometry.
2001 Jan
Sexual activity in hypertensive men treated with valsartan or carvedilol: a crossover study.
2001 Jan
Recovery of the cardiac adrenergic nervous system after long-term beta-blocker therapy in idiopathic dilated cardiomyopathy: assessment by increase in myocardial 123I-metaiodobenzylguanidine uptake.
2001 Jan
Current role of beta-adrenergic blockers in the treatment of chronic congestive heart failure.
2001 Jan 15
[Effects of carvedilol in rats with induced chronic kidney failure].
2001 Jan-Feb
Iodine-123 MIBG imaging before treatment of heart failure with carvedilol to predict improvement of left ventricular function and exercise capacity.
2001 Jan-Feb
Effects of carvedilol on left ventricular function, mass, and scintigraphic findings in isolated left ventricular non-compaction.
2001 Jul
Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts.
2001 Jul
Stereoselective effects of (R)- and (S)-carvedilol in humans.
2001 Jul
Radical-scavenging and iron-chelating properties of carvedilol, an antihypertensive drug with antioxidative activity.
2001 Jul 15
Using isoproterenol stress echocardiography to predict the response to carvedilol in patients with dilated cardiomyopathy.
2001 Jun
Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis.
2001 Jun
Bucindolol, a nonselective beta 1- and beta 2-adrenergic receptor antagonist, decreases beta-adrenergic receptor density in cultured embryonic chick cardiac myocyte membranes.
2001 Jun
Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001.
2001 Jun
A cost-effectiveness analysis of bisoprolol for heart failure.
2001 Jun
Differing beta-blocking effects of carvedilol and metoprolol.
2001 Jun
Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure.
2001 Jun
Carvedilol increases plasma vascular endothelial growth factor (VEGF) in patients with chronic heart failure.
2001 Jun
Beta-blocker trials seem to be in conflict.
2001 Jun 12
Beta-blockade in chronic heart failure.
2001 Jun 12
Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy.
2001 Jun 15
Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.
2001 Jun 22
Random research.
2001 Jun 26
[Options in drug combinations].
2001 Mar
[Adrenergic beta inhibitors in heart insufficiency: which and when?].
2001 Mar
Determination of carvedilol in human cardiac tissue by high-performance liquid chromatography.
2001 Mar
Predicting response to carvedilol for the treatment of heart failure: a multivariate retrospective analysis.
2001 Mar
Extracellular matrix proteins in cardiac fibroblasts derived from rat hearts with chronic pressure overload: effects of beta-receptor blockade.
2001 Mar
Does intention-to-treat analysis answer all questions in long-term mortality trials? Considerations on the basis of the ANZ trial.
2001 May
Mechanisms of carvedilol action in human congestive heart failure.
2001 May
Influence of carvedilol on hospitalizations in heart failure: incidence, resource utilization and costs. U.S. Carvedilol Heart Failure Study Group.
2001 May
Carvedilol in the treatment of chronic heart failure.
2001 May
Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure.
2001 May 22
Racial differences in the response to drugs--pointers to genetic differences.
2001 May 3
Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.
2001 May 3
Expanding indications for beta-blockers in heart failure.
2001 May 31
Effect of carvedilol on survival in severe chronic heart failure.
2001 May 31
Separation of carvedilol enantiomers in very small volumes of human plasma by capillary electrophoresis with laser-induced fluorescence.
2001 May 5
Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.
2001 May 5
Current role of beta-adrenergic blockers in the management of chronic heart failure.
2001 May 7
Economic impact of beta blockade in heart failure.
2001 May 7
Patents

Sample Use Guides

Take with food. Individualize dosage and monitor during up-titration.• Heart failure: Start at 3.125 mg twice daily and increase to 6.25, 12.5, and then 25 mg twice daily over intervals of at least 2 weeks. Maintain lower doses if higher doses are not tolerated.• Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then 25 mg twice daily afterintervals of 3 to 10 days. A lower starting dose or slower titration may be used.• Hypertension: Start at 6.25 mg twice daily and increase if needed for blood pressure control to 12.5 mg then 25 mg twice daily over intervals of 1 to 2 weeks.
Route of Administration: Oral
Compared with the PDGF-stimulated control, DNA synthesis decreased significantly to 60.3% +/- 10.4% and 18.3% +/- 5.9% in the presence of 1 and 10 microM of carvedilol, respectively (P < 0.05, each). Carvedilol significantly inhibited the activity of VSMCs stimulated by ET-1 and ANG-II. The IC50 of carvedilol was 1-10 microM. CsA only inhibited VSMCs significantly in the PDGF-stimulated subgroup. The addition of CsA in the presence of carvedilol did not affect the inhibitory activity of carvedilol. The pattern of inhibition in the combined group was uniform and similar to that of the carvedilol alone group, regardless of the stimulator used.
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:59:21 UTC 2021
Edited
by admin
on Sat Jun 26 08:59:21 UTC 2021
Record UNII
EQT531S367
Record Status Validated (UNII)
Record Version
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Name Type Language
CARVEDILOL PHOSPHATE
ORANGE BOOK   USAN   VANDF  
USAN  
Official Name English
SKF 105517D
Code English
CARVEDILOL PHOSPHATE HYDRATE [JAN]
Common Name English
CARVEDILOL DIHYDROGEN PHOSPHATE HEMIHYDRATE
Common Name English
CARVEDILOL PHOSPHATE HEMIHYDRATE
WHO-DD  
Common Name English
CARVEDILOL PHOSPHATE [VANDF]
Common Name English
2-PROPANOL, 1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO) , PHOSPHATE (SALT), HYDRATE (2:2:1)
Common Name English
COREG CR
Brand Name English
CARVEDILOL PHOSPHATE HYDRATE
JAN  
Common Name English
CARVEDILOL PHOSPHATE [USAN]
Common Name English
CARVEDILOL PHOSPHATE [ORANGE BOOK]
Common Name English
SKF-105517D
Code English
(2RS)-1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO)PROPAN-2-OL PHOSPHATE SALT (1:1) HEMIHYDRATE
Common Name English
SK&F-105517-D
Code English
CARVEDILOL PHOSPHATE HEMIHYDRATE [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29576
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
Code System Code Type Description
PUBCHEM
11954344
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
DRUG BANK
DBSALT001201
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
CAS
610309-89-2
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
RXCUI
668310
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C65292
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
FDA UNII
EQT531S367
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
EVMPD
SUB25804
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
ChEMBL
CHEMBL723
Created by admin on Sat Jun 26 08:59:21 UTC 2021 , Edited by admin on Sat Jun 26 08:59:21 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY