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Pronunciation
(KAR ve dil ole)
Generic Available (U.S.)
Yes: Tablet
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Mild-to-severe heart failure of ischemic or cardiomyopathic origin (usually in addition to standard therapy); left ventricular dysfunction following myocardial infarction (MI) (clinically stable with LVEF ≤40%); management of hypertension
Use: Unlabeled/Investigational
Angina pectoris
Pregnancy Risk Factor
C
Pregnancy Considerations
Because adverse events were not observed in animal reproduction studies, carvedilol is classified as pregnancy category C. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blockers during pregnancy. Intrauterine growth restriction (IUGR), small placentas, as well as fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. Carvedilol is not currently recommended for the initial treatment of maternal hypertension during pregnancy.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if carvedilol is excreted into human milk. The manufacturer suggests that a decision should be made to either discontinue nursing or discontinue the medication.
Contraindications
Serious hypersensitivity to carvedilol or any component of the formulation; decompensated cardiac failure requiring intravenous inotropic therapy; bronchial asthma or related bronchospastic conditions; second- or third-degree AV block, sick sinus syndrome, and severe bradycardia (except in patients with a functioning artificial pacemaker); cardiogenic shock; severe hepatic impairment
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery. Instruct patients to inform ophthalmologist of carvedilol use when considering eye surgery.
• Hypotension/syncope: Symptomatic hypotension with or without syncope may occur with carvedilol (usually within the first 30 days of therapy); close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Initiation with a low dose, gradual up-titration, and administration with food may help to decrease the occurrence of hypotension or syncope. Patients should be advised to avoid driving or other hazardous tasks during initiation of therapy due to the risk of syncope.
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms (eg, sweating, anxiety, tachycardia). In patients with heart failure and diabetes, use of carvedilol may worsen hyperglycemia; may require adjustment of antidiabetic agents.
• Heart failure (HF): Heart failure patients may experience a worsening of renal function (rare); risk factors include ischemic heart disease, diffuse vascular disease, underlying renal dysfunction, and systolic BP <100 mm Hg. In the severe chronic heart failure trials, patients were excluded if they had a baseline serum creatinine >2.8 mg/dL or increasing serum creatinine. Initiate cautiously and monitor for possible deterioration in patient status (eg, symptoms of HF). Worsening heart failure or fluid retention may occur during upward titration; dose reduction or temporary discontinuation may be necessary. Adjustment of other medications (ACE inhibitors and/or diuretics) may also be required.
• Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment; use is contraindicated in patients with severe hepatic impairment. Manufacturer recommends discontinuation of therapy if liver injury occurs (confirmed by laboratory testing).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD): May precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease; use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.
Concurrent drug therapy issues:
• Anesthetic agents: Use with caution in patients receiving anesthetic agents which decrease myocardial function.
• Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur.
Other warnings/precautions:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
Adverse Reactions
Note: Frequency ranges include data from hypertension and heart failure trials. Higher rates of adverse reactions have generally been noted in patients with heart failure. However, the frequency of adverse effects associated with placebo is also increased in this population.
>10%:
Cardiovascular: Hypotension (9% to 20%)
Central nervous system: Dizziness (2% to 32%), fatigue (4% to 24%)
Endocrine & metabolic: Hyperglycemia (5% to 12%)
Gastrointestinal: Weight gain (10% to 12%), diarrhea (1% to 12%)
Neuromuscular & skeletal: Weakness (7% to 11%)
1% to 10%:
Cardiovascular: Bradycardia (2% to 10%), syncope (3% to 8%), peripheral edema (1% to 7%), generalized edema (5% to 6%), angina (1% to 6%), dependent edema (≤4%), AV block, cerebrovascular accident, hypertension, hyper-/hypovolemia, postural hypotension, palpitation
Central nervous system: Headache (5% to 8%), depression, fever, hypoesthesia, hypotonia, insomnia, malaise, somnolence, vertigo
Endocrine & metabolic: Hypercholesterolemia (1% to 4%), hypertriglyceridemia (1%), diabetes mellitus, gout, hyperkalemia, hyperuricemia, hypoglycemia, hyponatremia
Gastrointestinal: Nausea (2% to 9%), vomiting (1% to 6%), abdominal pain, melena, periodontitis, weight loss
Genitourinary: Impotence
Hematologic: Anemia, prothrombin decreased, purpura, thrombocytopenia
Hepatic: Alkaline phosphatase increased (1% to 3%), GGT increased, transaminases increased
Neuromuscular & skeletal: Back pain (2% to 7%), arthralgia (1% to 6%), arthritis, muscle cramps, paresthesia
Ocular: Blurred vision (1% to 5%)
Renal: BUN increased (≤6%), nonprotein nitrogen increased (6%), albuminuria, creatinine increased, glycosuria, hematuria, renal insufficiency
Respiratory: Cough (5% to 8%), nasopharyngitis (4%), rales (4%), dyspnea (>3%), pulmonary edema (>3%), rhinitis (2%), nasal congestion (1%), sinus congestion (1%)
Miscellaneous: Injury (3% to 6%), allergy, flu-like syndrome, sudden death
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Anaphylactoid reaction, alopecia, aplastic anemia (rare, all events occurred in patients receiving other medications capable of causing this effect), amnesia, asthma, bronchospasm, bundle branch block, cholestatic jaundice, concentration decreased, diaphoresis, erythema multiforme, exfoliative dermatitis, GI hemorrhage, HDL decreased, hearing decreased, hyperbilirubinemia, hypokalemia, hypokinesia, interstitial pneumonitis, leukopenia, libido decreased, migraine, myocardial ischemia, nervousness, neuralgia, nightmares, pancytopenia, paresis, peripheral ischemia, photosensitivity, pruritus, rash (erythematous, maculopapular, and psoriaform), respiratory alkalosis, seizure, Stevens-Johnson syndrome, tachycardia, tinnitus, toxic epidermal necrolysis, urinary incontinence, xerostomia
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2C9 (major), CYP2D6 (major), CYP2E1 (minor), CYP3A4 (minor), P-glycoprotein; Inhibits P-glycoprotein
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification
Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk D: Consider therapy modification
Beta2-Agonists: Alpha-/Beta-Blockers may diminish the therapeutic effect of Beta2-Agonists. Risk D: Consider therapy modification
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy
Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Carvedilol. Risk C: Monitor therapy
Colchicine: P-Glycoprotein Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CycloSPORINE: Carvedilol may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Carvedilol may increase the serum concentration of CycloSPORINE (Systemic). Risk D: Consider therapy modification
CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Dabigatran Etexilate: P-Glycoprotein Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. According to Canadian labeling, dabigatran dose for prevention of venous thromboembolism post hip or knee replacement should be reduced to 150 mg/day in patients receiving amiodarone, verapamil, or quinidine. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Digoxin: Carvedilol may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Risk D: Consider therapy modification
Everolimus: P-Glycoprotein Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Lidocaine: Beta-Blockers may increase the serum concentration of Lidocaine. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy
Lidocaine (Topical): Beta-Blockers may decrease the metabolism of Lidocaine (Topical). Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Substrates: P-Glycoprotein Inhibitors may increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
Propoxyphene: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Rivaroxaban: P-Glycoprotein Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Alpha-/Beta-Blockers. Exceptions: FluvoxaMINE. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Topotecan: P-Glycoprotein Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Food decreases rate but not extent of absorption. Administration with food minimizes risks of orthostatic hypotension.
Herb/Nutraceutical: Avoid herbs with hypertensive properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng [American], kola, licorice); may diminish the antihypertensive effect of carvedilol. Avoid herbs with hypotensive properties (black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse); may enhance the hypotensive effect of carvedilol.
Storage
Coreg®: Store at <30°C (<86°F). Protect from moisture.
Coreg CR®: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
As a racemic mixture, carvedilol has nonselective beta-adrenoreceptor and alpha-adrenergic blocking activity. No intrinsic sympathomimetic activity has been documented. Associated effects in hypertensive patients include reduction of cardiac output, exercise- or beta-agonist-induced tachycardia, reduction of reflex orthostatic tachycardia, vasodilation, decreased peripheral vascular resistance (especially in standing position), decreased renal vascular resistance, reduced plasma renin activity, and increased levels of atrial natriuretic peptide. In CHF, associated effects include decreased pulmonary capillary wedge pressure, decreased pulmonary artery pressure, decreased heart rate, decreased systemic vascular resistance, increased stroke volume index, and decreased right arterial pressure (RAP).
Pharmacodynamics/Kinetics
Onset of action: 1-2 hours
Peak antihypertensive effect: ~1-2 hours
Absorption: Rapid and extensive
Distribution: Vd: 115 L
Protein binding: >98%, primarily to albumin
Metabolism: Extensively hepatic, via CYP2C9, 2D6, 3A4, and 2C19 (2% excreted unchanged); three active metabolites (4-hydroxyphenyl metabolite is 13 times more potent than parent drug for beta-blockade); first-pass effect; plasma concentrations in the elderly and those with cirrhotic liver disease are 50% and 4-7 times higher, respectively
Bioavailability: Immediate release: 25% to 35% (due to significant first-pass metabolism); Extended release: 85% of immediate release
Half-life elimination: 7-10 hours
Time to peak, plasma: Extended release: 5 hours
Excretion: Primarily feces
Dosage
Oral: Adults: Reduce dosage if heart rate drops to <55 beats/minute.
Hypertension:
Immediate release: 6.25 mg twice daily; if tolerated, dose should be maintained for 1-2 weeks, then increased to 12.5 mg twice daily. If necessary, dosage may be increased to a maximum of 25 mg twice daily after 1-2 weeks.
Extended release: Initial: 20 mg once daily, if tolerated, dose should be maintained for 1-2 weeks then increased to 40 mg once daily if necessary; maximum dose: 80 mg once daily
Heart failure:
Immediate release: 3.125 mg twice daily for 2 weeks; if this dose is tolerated, may increase to 6.25 mg twice daily. Double the dose every 2 weeks to the highest dose tolerated by patient. (Prior to initiating therapy, other heart failure medications should be stabilized and fluid retention minimized.)
Maximum recommended dose:
Mild-to-moderate heart failure:
<85 kg: 25 mg twice daily
>85 kg: 50 mg twice daily
Severe heart failure: 25 mg twice daily
Extended release: Initial: 10 mg once daily for 2 weeks; if the dose is tolerated, increase dose to 20 mg, 40 mg, and 80 mg over successive intervals of at least 2 weeks. Maintain on lower dose if higher dose is not tolerated.
Left ventricular dysfunction following MI: Note: Should be initiated only after patient is hemodynamically stable and fluid retention has been minimized.
Immediate release: Initial 3.125-6.25 mg twice daily; increase dosage incrementally (ie, from 6.25-12.5 mg twice daily) at intervals of 3-10 days, based on tolerance, to a target dose of 25 mg twice daily.
Extended release: Initial: 10-20 mg once daily; increase dosage incrementally at intervals of 3-10 days, based on tolerance, to a target dose of 80 mg once daily.
Angina pectoris (unlabeled use): Immediate release: 25-50 mg twice daily
Elderly: Hypertension: Consider lower initial dose and titrate to response (Aronow, 2011)
Conversion from immediate release to extended release (Coreg CR®):
Current dose immediate release tablets 3.125 mg twice daily: Convert to extended release capsules 10 mg once daily
Current dose immediate release tablets 6.25 mg twice daily: Convert to extended release capsules 20 mg once daily
Current dose immediate release tablets 12.5 mg twice daily: Convert to extended release capsules 40 mg once daily
Current dose immediate release tablets 25 mg twice daily: Convert to extended release capsules 80 mg once daily
Dosing adjustment in renal impairment: None necessary
Dosing adjustment in hepatic impairment: Use is contraindicated in severe liver dysfunction.
Administration: Oral
Administer with food to minimize the risk of orthostatic hypotension. Extended release capsules should not be crushed or chewed. Capsules may be opened and sprinkled on applesauce for immediate use.
Monitoring Parameters
Heart rate, blood pressure (base need for dosage increase on trough blood pressure measurements and for tolerance on standing systolic pressure 1 hour after dosing); renal studies, BUN, liver function; in patient with increase risk for developing renal dysfunction, monitor during dosage titration.
Dietary Considerations
Should be taken with food to minimize the risk of orthostatic hypotension.
Patient Education
Take pulse daily, prior to taking medication; follow prescriber's instruction about holding medication. If you have diabetes, monitor serum glucose closely (drug may alter glucose tolerance or mask signs of hypoglycemia). You may experience fatigue, dizziness, or postural hypotension. Report unresolved swelling of extremities; respiratory difficulty or new cough; unresolved fatigue; or unusual weight gain.
Geriatric Considerations
Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. In U.S. trials conducted by the manufacturer, hypertension patients who were elderly (>65%) had a higher incidence of dizziness (8.8% vs 6%) than seen in younger patients. No other differences noted between young and old in these trials.
Additional Information
Fluid retention during therapy should be treated with an increase in diuretic dosage.
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information:
Surgery: The ACCF/AHA 2009 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery recommend beta-blockers be continued in patients undergoing surgery who are receiving beta-blockers to treat ACCF/AHA Class I guideline indications such as angina, symptomatic arrhythmias, or hypertension (Class I recommendation).
The majority of published trials suggest a benefit of perioperative beta-blocker use during noncardiac surgery especially in high-risk patients; however, more recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery especially when higher fixed-dose regimens are employed (Juul, 2006; POISE study group, 2008; Yang, 2006). Therefore, the guidelines suggest that perioperative beta-blocker therapy titrated to goal heart rate and blood pressure may be beneficial to patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgeries who have coronary artery disease identified or are at high cardiac risk (Class IIa recommendation). High cardiac risk is defined as having >1 of the following clinical risk factors: History of ischemic heart disease, compensated or prior heart failure, cerebrovascular disease, diabetes mellitus, or renal insufficiency (serum creatinine: >2 mg/dL). The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ≤1 clinical risk factor (Class IIb recommendation). Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to adequate heart rate control (eg, between 60-80 beats per minute) while avoiding clinically significant bradycardia and hypotension. Routine administration of high fixed-dose beta-blockade without dose titration is not useful and may be harmful to beta-blocker naïve patients undergoing noncardiac surgery.
Cardiovascular Considerations
Atrial Fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.
Chronic Stable Angina: Beta-blockers are effective in the treatment of chronic stable angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.
Heart Failure: Strong evidence supports that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). Carvedilol is a nonselective beta-blocker with alpha-blocking and antioxidant properties. To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration. Because carvedilol has alpha-adrenergic blocking effects, it may lower blood pressure to a greater extent. The definitive clinical benefits of the antioxidant property are not known at this time.
Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. According to the 2003 JNC-VII guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists that requires the use of other drugs, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Beta-blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for a beta-blocker include patients with heart failure, postmyocardial infarction, high coronary disease risk, or diabetes. In type 2 diabetic patients, a UK Prospective Diabetes Study Group (UKPDS) trial showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
ST-Segment Elevation Myocardial Infarction (STEMI): Beta-blockers, without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of STEMI and continued long-term. Oral beta-blockade should be initiated promptly in patients without contraindications (eg, signs of heart failure, evidence of a low output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade may be considered and given promptly if the patient is experiencing concomitant hypertension or a tachyarrhythmia (Class IIa recommendation).
Unstable Angina/Non-ST-Segment Elevation MI (UA/NSTEMI): In the treatment of UA/NSTEMI, oral beta-blockade should be initiated within the first 24 hours in patients without contraindications (eg, signs of heart failure, evidence of a low output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade should only be considered if the patient is experiencing concomitant hypertension upon presentation (Class IIa recommendation).
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Postural hypotension. Periodontitis has been reported in product labeling for carvedilol; no other reports have confirmed this effect; any possible mechanism for this effect is unknown. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause fatigue, insomnia, confusion, and nightmare and clinically look like a major depression
Mental Health: Effects on Psychiatric Treatment
Fluoxetine and paroxetine may increase carvedilol's (a CYP2D6 substrate) serum levels
Nursing: Physical Assessment/Monitoring
Blood pressure and heart rate should be assessed prior to and following first dose and any change in dose. Caution patients with diabetes to monitor glucose levels closely (beta-blockers may alter glucose tolerance).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral, as phosphate:
Coreg CR®: 10 mg, 20 mg, 40 mg, 80 mg
Tablet, oral: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg
Coreg®: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Coreg CR)
10 mg (30): $141.99
20 mg (30): $141.99
40 mg (30): $141.99
80 mg (30): $141.99
Tablets (Carvedilol)
3.125 mg (30): $25.99
6.25 mg (30): $14.99
12.5 mg (30): $14.99
25 mg (30): $15.99
Tablets (Coreg)
3.125 mg (60): $138.99
6.25 mg (30): $74.99
12.5 mg (60): $149.00
25 mg (60): $157.99
Extemporaneously Prepared
A 1.25 mg/mL carvedilol oral suspension may be made with tablets and one of two different vehicles (Ora-Blend™ or 1:1 mixture of Ora-Sweet® and Ora-Plus®). Crush five 25 mg tablets in a mortar and reduce to a fine powder; add 15 mL of purified water and mix to a uniform paste. Mix while adding chosen vehicle in incremental proportions to almost 100 mL; transfer to a calibrated amber bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 100 mL. Label “shake well”. Stable for 84 days when stored in amber prescription bottles at room temperature (Loyd, 2006).
Carvedilol oral liquid suspensions (0.1 mg/mL and 1.67 mg/mL) made from tablets, water, Ora-Plus®, and Ora-Sweet® were stable for 12 weeks when stored in glass amber bottles at room temperature (25°C). Use one 3.125 mg tablet for the 0.1 mg/mL suspension or two 25 mg tablets for the 1.67 mg/mL suspension; grind the tablet(s) and compound a mixture with 5 mL of water, 15 mL Ora-Plus®, and 10 mL Ora-Sweet®. Final volume of each suspension: 30 mL; label “shake well” (data on file, GlaxoSmithKline, Philadelphia, PA: DOF #132 [Note: Manufacturer no longer disseminates this document]).
Loyd A Jr, “Carvedilol 1.25 mg/mL Oral Suspension,” Int J Pharm Compounding, 2006, 10(3):220.
References
Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine,” J Am Coll Cardiol, 2007, 50(7):e1-e157.
Antman EM, Anbe DT, Armstrong PW, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction),” Circulation, 2004, 110(9):e82-292.
Antman EM, Hand M, Armstrong PW, et al, “2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines,” J Am Coll Cardiol, 2008, 51(2):210-49.
Aronow WS, Fleg JL, Pepine CJ, et al, “ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” Circulation, 2011 [epub ahead of print].
Brauchli YB, Jick SS, Curtin F, et al, “Association Between Beta-Blockers, Other Antihypertensive Drugs and Psoriasis: Population-Based Case-Control Study,” Br J Dermatol, 2008, 158(6):1299-307.
Bristow MR, Gilbert EM, Abraham WT, et al, “Carvedilol Produces Dose-Related Improvements in Left Ventricular Function and Survival in Subjects With Chronic Heart Failure,” Circulation, 1996, 94(11):2807-16.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Colucci WS, Packer M, Bristow MR, et al, “Carvedilol Inhibits Clinical Progression in Patients With Mild Symptoms of Heart Failure. U.S Carvedilol Heart Failure Study Group,” Circulation, 1996, 94(11):2800-6.
Dargie HJ, “Effect of Carvedilol on Outcome After Myocardial Infarction in Patients With Left-Ventricular Dysfunction: The CAPRICORN Randomised Trial,” Lancet, 2001, 357(9266):1385-90.
Eagle KA, Guyton RA, Davidoff R, et al, “ACC/AHA 2004 Guideline Update for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery),” Circulation, 2004, 110(14):e340-437.
Fleisher LA, Beckman JA, Brown KA, et al, “2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” J Am Coll Cardiol, 2009, 54(22):e13-118.
Fraker TD, Fihn SD, Gibbons RJ, et al, “2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to Develop the Focused Update of the 2002 Guidelines for the Management of Patients With Chronic Stable Angina,” Circulation, 2007, 116(23):2762-72.
Gibbons RJ, Abrams J, Chatterjee K, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),” J Am Coll Cardiol, 2003, 41(1):159-68.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Juul AB, Wetterslev J, Gluud C, et al, “Effect of Perioperative Beta-Blockade in Patients With Diabetes Undergoing Major Non-Cardiac Surgery: Randomized Placebo Controlled, Blinded Multicentre Trial,” BMJ, 2006, 332(7556):1482.
Lang DM, “Anaphylactoid and Anaphylactic Reactions. Hazards of Beta-Blockers,” Drug Saf, 1995, 12(5):299-304.
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
Macdonald PS, Keogh AM, Aboyoun CL, et al, “Tolerability and Efficacy of Carvedilol in Patients With New York Heart Association Class IV Heart Failure,” J Am Coll Cardiol, 1999, 33(4):924-31.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Packer M, Bristow MR, Cohn JN, et al, “The Effect of Carvedilol on Morbidity and Mortality in Patients With Chronic Heart Failure. U.S. Carvedilol Heart Failure Study Group,” N Engl J Med, 1996, 334(21):1349-55.
Packer M, Coats AJ, Fowler MB, et al, “Effect of Carvedilol on Survival in Severe Chronic Heart Failure,” N Engl J Med, 2001, 344(22):1651-8.
Packer M, Colucci WS, Sackner-Bernstein JD, et al, “Double-Blind, Placebo-Controlled Study of the Effects of Carvedilol in Patients With Moderate to Severe Heart Failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise,” Circulation, 1996, 94(11):2793-9.
POISE Study Group, Devereaux PJ, Yang H, et al, “Effects of Extended-Release Metoprolol Succinate in Patients Undergoing Non-Cardiac Surgery (POISE Trial): A Randomised Controlled Trial,” Lancet, 2008, 371(9627):1839-47.
“Randomised, Placebo-Controlled Trial of Carvedilol in Patients With Congestive Heart Failure Due to Ischaemic Heart Disease. Australia/New Zealand Heart Failure Research Collaborative Group,” Lancet, 1997, 349(9049):375-80.
Redelmeier D, Scales D, and Kopp A, "Beta Blockers for Elective Surgery in Elderly Patients: Population Based, Retrospective Cohort Study," BMJ, 2005, 331(7522):932.
Schön MP and Boehncke WH, “Psoriasis,” N Eng J Med, 2005, 352(18):1899-1912.
UK Prospective Diabetes Study Group, “Efficacy of Atenolol and Captopril in Reducing Risk of Macrovascular and Microvascular Complications in Type 2 Diabetes: UKPDS 39,” BMJ, 1998, 317(7160):713-20.
Yang H, Raymer K, Butler R, et al, “The Effects of Perioperative Beta-Blockade: Results of the Metoprolol After Vascular Surgery (MaVS) Study, A Randomized Controlled Trial,” Am Heart J 2006, 152(5):983-90.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2011
Content last modified June 2011
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