carvedilol (Coreg)
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Introduction
Tradename: Coreg.
Indications
- heart failure* NYHA class II or III
- use in conjunction with digoxin, diuretic & ACE inhibitor
- angina pectoris in patients with idiopathic cardiomyopathy
- decreased left ventricular function after myocardial infarction[6]
- may protect against microabuminuria in patients with diabetes mellitus type 2[8]
- hypertension[10]
* may be useful in patients with NYHA class IV heart failure[4]
Contraindications
- asthma or bronchospastic disease
- uncompensated congestive heart failure (NYHA class IV)
- cardiogenic shock
- severe bradycardia
- 2nd or 3rd degree heart block
- symptomatic hepatic disease
- pregnancy*
* contraception indicated during therapy
Dosage
- all dosages should be taken with food
- start 3.125 mg PO BID for 2 weeks
- if tolerated, increase to 6.25 mg PO BID
- double dose every 2 weeks until maximum tolerated dose is reached
- max dose 25 mg PO BID if < 85 kg, 50 mg BID if > 85 kg
Extended release: Coreg CR (QD dosing)
- do NOT crush or chew the caps
- CAN open them & sprinkle the beads on applesauce
- diminished bioavailability relative to Coreg: conversion Coreg 6.25 mg BID -> Coreg CR 20 mg QD Coreg 12.5 mg BID -> Coreg CR 40 mg QD
Pharmacokinetics
- oral bioavailability is 25-30% secondary to 1st pass effect
- protein-binding > 98%
- metabolized by cyt P450 2D6 & cyt P450 2C9
- metabolites excreted primarily in feces & bile
- poorly dialyzable[11]
elimination via liver
protein binding = >98 %
Adverse effects
- common (> 10%)
- less common (1-10%)
- uncommon (< 1%)
- AV block, palpitations, peripheral ischemia, syncope, ataxia, vertigo, depression, nervousness, malaise, pruritus, rash, decreased libido (male), constipation, hypercholesterolemia*, hyperuricemia, flatulence, xerostomia, impotence, anemia, leukopenia, increased LFTs, hyperbilirubinemia, paresthesias, myalgias, weakness, abnormal vision, tinnitus, asthma, cough
* less tendency to cause hyperglycemia & dyslipidemia than metoprolol because of alpha-blocking[7]
- drug adverse effects of beta-adrenergic receptor antagonists
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of antihypertensive agents
Drug interactions
- dizziness with coadministration of cyt P450 2D6 inhibitors
- decreased levels with coadministration of cyt P450 2D6 inducers
- rifampin (70% reduction of carvedilol levels)
- carvedilol may enhance the effects of hypoglycemic agents
- conduction disturbance with concurrent administration of calcium channel blockers
- clonidine may potentiate hypotensive & bradycardic effects
- carvedilol increases digoxin levels 15%
- cimetidine increases carvedilol levels by 30%
- paroxetine, fluoxetine & amiodarone may increase carvedilol levels
- any drug which inhibits cyt P450 2C9 or 2D6 can increase carvedilol levels
- any drug which induces cyt P450 2C9 or cyt P450b 2D6 can diminish carvedilol levels
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of beta-2 adrenergic receptor agonists with beta adrenergic receptor antagonists
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of beta-adrenergic receptor antagonists with thyroid hormone
- drug interaction(s) of beta-adrenergic receptor antagonists with sulfinpyrazone
- drug interaction(s) of beta-adrenergic receptor antagonists with salicylate
- drug interaction(s) of beta-adrenergic receptor antagonists with rifampin
- drug interaction(s) of beta-adrenergic receptor antagonists with ampicillin
- drug interaction(s) of beta-adrenergic receptor antagonists with colestipol
- drug interaction(s) of beta-adrenergic receptor antagonists with cholestyramine
- drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium salts
- drug interaction(s) of beta-adrenergic receptor antagonists with aluminum carbonate
- drug interaction(s) of beta-adrenergic receptor antagonists with aluminum hydroxide
- drug interaction(s) of beta-adrenergic receptor antagonists with prazosin
- drug interaction(s) of beta-adrenergic receptor antagonists with lidocaine
- drug interaction(s) of beta-adrenergic receptor antagonists with ergot alkaloids
- drug interaction(s) of beta-adrenergic receptor antagonists with clonidine
- drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists (except atenolol) with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists with quinolones
- drug interaction(s) of beta-adrenergic receptor antagonists with quinidine
- drug interaction(s) of beta-adrenergic receptor antagonists with propafenone
- drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines
- drug interaction(s) of beta-adrenergic receptor antagonists with MAO inhibitors
- drug interaction(s) of beta-adrenergic receptor antagonists with loop diuretics
- drug interaction(s) of beta-adrenergic receptor antagonists with hydralazine
- drug interaction(s) of beta-adrenergic receptor antagonists with histamine H2 receptor antagonists
- drug interaction(s) of beta-adrenergic receptor antagonists with haloperidol
- drug interaction(s) of beta-adrenergic receptor antagonists with flecainide
- drug interaction(s) of beta-adrenergic receptor antagonists with oral contraceptives
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium channel blockers
- drug interaction(s) of beta-adrenergic receptor antagonists with sulfonylureas
- drug interaction(s) of beta blockers with ACE inhibitors
- drug interaction(s) of spironolactone with beta blockers
- drug interaction(s) of NSAIDs with beta blockers
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- racemic mixture of
- non-selective beta-adrenergic receptor antagonist activity in S(-) enantiomer &
- alpha-1-adrenergic receptor antagonist activity in both enantiomers
- diminished cardiac output
- diminished exercise-induced tachycardia
- diminished reflex-induced tachycardia
- induces vasodilation
- reduces peripheral vascular resistance
- has anti-oxidant effects on ischemic tissue
- reduces mortality (23%) after MI
More general terms
Additional terms
- cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
References
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
restricted to patients with CHF - ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 4.0 4.1 Journal Watch 23(6):46, 2003 Krum H, Roecker EB, Mohacsi P et al, Effects of initiating carvedilol in patients with severe chronic heart failure: results from the COPERNICUS Study. JAMA. 2003 Feb 12;289(6):712-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12585949
- ↑ Galaxo
- ↑ 6.0 6.1 Prescriber's Letter 10(7):37 2003
- ↑ 7.0 7.1 Prescriber's Letter 12(1): 2005 Carvedilol: is it a Better Choice in Patients with Diabetes? Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210102&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 Internal Medicine News, April 15, 2005
- ↑ Prescriber's Letter 14(3): 2007 New Formulation: Coreg CR (Carvedilol Extended-release) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230305&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 Deprecated Reference
- ↑ 11.0 11.1 Zhou H et al beta-blocker use and risk of mortality in heart failure patients initiating maintenance dialysis. Am J Kidney Dis 2021 May; 77:704 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33010357 https://www.ajkd.org/article/S0272-6386(20)31001-5/fulltext