CARVEDILOL HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H26N2O4.ClH
Molecular Weight	442.935
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=C(OCCNCC(O)COC2=CC=CC3=C2C4=C(N3)C=CC=C4)C=CC=C1

InChI

InChIKey=OSZYHTJPTLLICF-UHFFFAOYSA-N

InChI=1S/C24H26N2O4.ClH/c1-28-21-10-4-5-11-22(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;/h2-12,17,25-27H,13-16H2,1H3;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23506034 | https://www.ncbi.nlm.nih.gov/pubmed/9211087 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020297s029lbl.pdf

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor beta 87 Target ID: CHEMBL2094118 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1378154 \| https://www.ncbi.nlm.nih.gov/pubmed/1350478	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Heart failure 103 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020297s029lbl.pdf	Primary	Approved 8429	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 1995
Myocardial infarction 121 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020297s029lbl.pdf	Primary	Approved 8429	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 1995
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020297s029lbl.pdf	Primary	Approved 8429	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 1995

C_max

Value	Dose	Analyte	Population
18.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668	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

Value	Dose	Analyte	Population
94.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668	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

Dose	Population	Adverse events
300 mg single, oral Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Co-administed with:: lorazepam(7 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/31988787	unknown, 41 years n = 1 Health Status: unknown Age Group: 41 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/31988787	Other AEs: Wheezing... Other AEs: Wheezing (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31988787
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: https://pubmed.ncbi.nlm.nih.gov/22240593	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: https://pubmed.ncbi.nlm.nih.gov/22240593	Sources: https://pubmed.ncbi.nlm.nih.gov/22240593
375 mg single, oral Overdose Dose: 375 mg Route: oral Route: single Dose: 375 mg Co-administed with:: simvastatin(fifteen 20-mg tablets) Sources: https://pubmed.ncbi.nlm.nih.gov/18598302	unhealthy, 84 years n = 1 Health Status: unhealthy Age Group: 84 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18598302	Other AEs: Hypotension... Other AEs: Hypotension (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18598302
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf	unhealthy, adult n = 765 Health Status: unhealthy Condition: heart failure Age Group: adult Population Size: 765 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf	Disc. AE: Hypotension... AEs leading to discontinuation/dose reduction: Hypotension (0.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf
20 mg 2 times / day multiple, oral Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	Disc. AE: Congestive cardiac failure... AEs leading to discontinuation/dose reduction: Congestive cardiac failure (moderate, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf	unhealthy, adult n = 1156 Health Status: unhealthy Condition: severe heart failure Age Group: adult Population Size: 1156 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf	Disc. AE: Dizziness... AEs leading to discontinuation/dose reduction: Dizziness (1.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	Disc. AE: Abdominal distension... AEs leading to discontinuation/dose reduction: Abdominal distension (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (moderate, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/31988787	unknown, 41 years n = 1 Health Status: unknown Age Group: 41 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/31988787
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: https://pubmed.ncbi.nlm.nih.gov/18598302	unhealthy, 84 years n = 1 Health Status: unhealthy Age Group: 84 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18598302
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf	unhealthy, adult n = 765 Health Status: unhealthy Condition: heart failure Age Group: adult Population Size: 765 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf	unhealthy, adult n = 1156 Health Status: unhealthy Condition: severe heart failure Age Group: adult Population Size: 1156 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s038lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61	unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/022012s000_MedR_P1.pdf Page: p. 61

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3441	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3441
ChemicalBook	CB8351959	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8351959
MolPort	MolPort-003-666-814	https://www.molport.com/shop/molecule-link/MolPort-003-666-814
Selleck Chemicals	carvedilol	http://www.selleckchem.com/products/carvedilol.html
eMolecules	901524	https://www.emolecules.com/cgi-bin/more?vid=901524

PubMed

Title	Date	PubMed
Levosimendan.	2001	11368286
CAPRICORN: a story of alpha allocation and beta-blockers in left ventricular dysfunction post-MI.	2001 Apr	11334653
Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium.	2001 Apr	11309254
Carvedilol as therapy in pediatric heart failure: an initial multicenter experience.	2001 Apr	11295713
Carvedilol--a new dimension in pediatric heart failure therapy.	2001 Apr	11295704
50th Annual scientific sessions of the American college of cardiology.	2001 Apr 10	11294821
Reducing readmissions for congestive heart failure.	2001 Apr 15	11327436
Detection of low levels of the amorphous phase in crystalline pharmaceutical materials by thermally stimulated current spectrometry.	2001 Jan	11336360
[Effects of carvedilol in rats with induced chronic kidney failure].	2001 Jan-Feb	11344962
Effects of carvedilol on left ventricular function, mass, and scintigraphic findings in isolated left ventricular non-compaction.	2001 Jul	11410581
Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts.	2001 Jul	11406463
Stereoselective effects of (R)- and (S)-carvedilol in humans.	2001 Jul	11400186
Radical-scavenging and iron-chelating properties of carvedilol, an antihypertensive drug with antioxidative activity.	2001 Jul 15	11389884
Using isoproterenol stress echocardiography to predict the response to carvedilol in patients with dilated cardiomyopathy.	2001 Jun	11407733
Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis.	2001 Jun	11401736
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	11392464
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	11378012
A cost-effectiveness analysis of bisoprolol for heart failure.	2001 Jun	11378009
Differing beta-blocking effects of carvedilol and metoprolol.	2001 Jun	11378006
Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure.	2001 Jun	11378005
Carvedilol increases plasma vascular endothelial growth factor (VEGF) in patients with chronic heart failure.	2001 Jun	11378004
Plasma brain natriuretic peptide as a novel therapeutic indicator in idiopathic dilated cardiomyopathy during beta-blocker therapy: a potential of hormone-guided treatment.	2001 Jun	11376305
Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis.	2001 Jun	11376302
Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.	2001 Jun 1	11401111
Protective effect of carvedilol on chenodeoxycholate induction of the permeability transition pore.	2001 Jun 1	11331081
Beta-blocker trials seem to be in conflict.	2001 Jun 12	11401953
Beta-blockade in chronic heart failure.	2001 Jun 12	11401950
Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy.	2001 Jun 15	11419892
Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.	2001 Jun 22	11430928
Random research.	2001 Jun 26	11425783
[Options in drug combinations].	2001 Mar	11409073
[Adrenergic beta inhibitors in heart insufficiency: which and when?].	2001 Mar	11409070
Determination of carvedilol in human cardiac tissue by high-performance liquid chromatography.	2001 Mar	11277253
[Severe heart failure. Carvedilol lowers mortality].	2001 Mar 1	11288541
Benefits of beta-blockers in heart failure: a class specific effect?	2001 May	11392635
Does intention-to-treat analysis answer all questions in long-term mortality trials? Considerations on the basis of the ANZ trial.	2001 May	11380066
Mechanisms of carvedilol action in human congestive heart failure.	2001 May	11358931
Overview of the results of recent beta blocker trials.	2001 May	11357013
Influence of carvedilol on hospitalizations in heart failure: incidence, resource utilization and costs. U.S. Carvedilol Heart Failure Study Group.	2001 May	11345386
Carvedilol in the treatment of chronic heart failure.	2001 May	11336626
Carvedilol versus other beta-blockers in heart failure.	2001 May	11322870
Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure.	2001 May 22	11369683
Racial differences in the response to drugs--pointers to genetic differences.	2001 May 3	11336055
Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.	2001 May 3	11333992
Expanding indications for beta-blockers in heart failure.	2001 May 31	11386271
Effect of carvedilol on survival in severe chronic heart failure.	2001 May 31	11386263
Separation of carvedilol enantiomers in very small volumes of human plasma by capillary electrophoresis with laser-induced fluorescence.	2001 May 5	11393694
Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.	2001 May 5	11356434
Current role of beta-adrenergic blockers in the management of chronic heart failure.	2001 May 7	11334782
Economic impact of beta blockade in heart failure.	2001 May 7	11334781

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Name

Type

Language

CARVEDILOL HYDROCHLORIDE

Common Name

English

CARVEDILOL MONOHYDROCHLORIDE

Common Name

English

Carvedilol hydrochloride [WHO-DD]

Common Name

English

2-PROPANOL, 1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO)-, HYDROCHLORIDE (1:1)

Systematic Name

English

2-PROPANOL, 1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO)-, MONOHYDROCHLORIDE

Common Name

English

Code System Code Type Description

EVMPD

SUB01074MIG