Carvedilol (Lexi-Drugs)

Pronunciation

(KAR ve dil ole)

Brand Names: US

Coreg; Coreg CR

Brand Names: Canada

APO-Carvedilol; Auro-Carvedilol; DOM-Carvedilol; JAMP-Carvedilol; MYLAN-Carvedilol [DSC]; NOVO-Carvedilol [DSC]; NU-Carvedilol [DSC]; PMS-Carvedilol; RAN-Carvedilol; TEVA-Carvedilol

Dosing: Adult

Reduce dosage if heart rate drops to <55 beats/minute.

Hypertension (alternative agent): Oral:

Immediate release: Initial: 6.25 mg twice daily; titrate dose every 1 to 2 weeks as needed based on patient response up to a maximum of 25 mg twice daily (ACC/AHA [Whelton 2017]).

Extended release: Initial: 20 mg once daily; titrate dose every 1 to 2 weeks as needed based on patient response up to 80 mg once daily (ACC/AHA [Whelton 2017]); maximum dose: 80 mg/day

Heart failure with reduced ejection fraction (HFrEF): Note: Initiate only in stable patients. In hospitalized patients, initiate after volume status has been optimized and IV diuretics, vasodilators, and inotropic agents have been successfully discontinued. Use caution when initiating in patients with NYHA class IV symptoms or recent HF exacerbation (particularly if inotropes were required during their hospital course) (ACCF/AHA [Yancy 2013]; Colucci 2018).

Immediate release: 3.125 mg twice daily for 2 weeks; if this dose is tolerated, may increase to 6.25 mg twice daily. Up-titrate gradually (eg, doubling the dose every 2 weeks or more) to the maximum tolerated dose while monitoring for signs and symptoms of HF (ACCF/AHA [Yancy 2013]; ACC/AHA/HFSA [Yancy 2017]; Packer 1996a; Packer 2001).

Maximum recommended dose:

≤85 kg: 25 mg twice daily

>85 kg: 50 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 to the maximum tolerated dose; maximum dose: 80 mg/day (ACCF/AHA [Yancy 2013]; ACC/AHA/HFSA [Yancy 2017]).

Left ventricular dysfunction following MI: Oral: Note: Should be initiated only after patient is hemodynamically stable and fluid retention has been minimized.

Immediate release: Initial 3.125 to 6.25 mg twice daily; increase dosage incrementally (ie, from 6.25 to 12.5 mg twice daily) at intervals of 3 to 10 days, based on tolerance, to a target dose of 25 mg twice daily. Note: The 2013 ACCF/AHA heart failure guidelines recommend a maximum dose of 50 mg twice daily (Yancy 2013].

Extended release: Initial: 10 to 20 mg once daily; increase dosage incrementally at intervals of 3 to 10 days, based on tolerance, to a target dose of 80 mg once daily.

Angina pectoris (off-label use): Oral: Immediate release: 25 to 50 mg twice daily

Atrial fibrillation (rate control) (off-label use): Usual maintenance dose: 3.125 to 25 mg twice daily (AHA/ACC/HRS [January 2014]). In patients with heart failure, the initial dose of 3.125 mg twice daily may be increased at 2-week intervals to a target dose of 25 mg twice daily (50 mg twice daily for patients weighing >85 kg) (Khand 2003)

Gastroesophageal variceal hemorrhage prophylaxis in patients with cirrhosis (alternative agent) (off-label use): Oral: Initial: 3.125 mg twice daily or 6.25 mg once daily; to achieve a resting heart rate of 55 to 60 bpm (if heart rate used for titration), may increase after 3 to 7 days to a maximum dose of 6.25 mg twice daily or 12.5 mg once daily (some patients [eg, with Child-Pugh class A cirrhosis or those with persistent arterial hypertension] may receive a maximum dose of 12.5 mg twice daily) (Baiges 2017; Bhardwaj 2017; Garcia-Tsao 2016; LaBrecque 2014; Sanyal 2018; Tripathi 2009). Note: Higher doses (eg, >12.5 mg/day) may decrease arterial pressure and should not be used in patients with refractory ascites. Use is not recommended for recurrent variceal hemorrhage (Garcia-Tsao 2016).

Ventricular arrhythmias (offlabel use): Oral: Immediate release: 3.125 to 25 mg twice daily (AHA/ACC/HRS [Al-Khatib 2017])

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: Geriatric

Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow, 2011).

Dosing: Renal Impairment: Adult

No dosage adjustment necessary; not significantly cleared by hemodialysis

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Severe impairment: Use is contraindicated.

Dosing: Pediatric

Note: Immediate release and extended release products are not interchangeable on a mg:mg basis due to pharmacokinetic differences. Individualize dosage for each patient; monitor patients closely during initiation and upwards titration of dose; reduce dosage for hypotension or bradycardia (adolescents ≥ 18 years: 55 bpm; younger patients may alternate target). Pharmacokinetic data suggests a faster carvedilol elimination in young pediatric patients (< 3.5 years) which may require more frequent dosing (3 times daily) and a higher target dose per kg (Laer, 2002; Shaddy, 2007).

Heart failure: Prior to initiating therapy, other CHF medications should be stabilized and fluid retention minimized.

Infants, Children, and Adolescents ≤ 17 years: Limited data available, efficacy results variable; optimal dose not established: Oral: Immediate release tablets: Initial: Reported mean: 0.075-0.08 mg/kg/dose twice daily; titrate as tolerated; may increase dose by typically 50% every 2 weeks; usual reported maintenance (target) dose range: 0.3-0.75 mg/kg/dose twice daily; the usual titration time to reach target dose was 11-14 weeks (Bruns, 2001; Rusconi, 2004); maximum daily dose: 50 mg/day. Dosing based on two retrospective analyses of a total 70 pediatric patients (age range: 3 months to 19 years) which showed improvement in left ventricular function and heart failure symptoms (67% to 68% of patients showed improvement in NYHA class). However, in a large, a multicenter, double-blind, placebo-controlled, dose-finding trial in 161 pediatric patients (treatment group: n=103, median age range: 33-43 months), a lower target dose range of 0.2-0.4 mg/kg/dose twice daily did not result in a statistical difference in composite clinical end point scores compared to placebo; the authors suggested multiple factors for negative efficacy findings including that the study may have been underpowered due to unexpected, high improvement of the placebo-arm; a subset analysis suggests ventricular morphology may play a role in efficacy (Shaddy, 2007).

Adolescents ≥18 years:

Immediate release tablets: Oral: Initial: 3.125 mg twice daily for 2 weeks; if tolerated, may increase to 6.25 mg twice daily. May double the dose every 2 weeks to the highest dose tolerated by patient.

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 capsules: Oral: Initial: 10 mg once daily for 2 weeks; if tolerated, may double the dose (eg, 20 mg, 40 mg) every 2 weeks up to 80 mg once daily; maintain on lower dose if higher dose is not tolerated

Hypertension: Adolescents ≥18 years:

Immediate release tablets: Oral: Initial: 6.25 mg twice daily; if tolerated, dose should be maintained for 1-2 weeks, then increased to 12.5 mg twice daily; maximum daily dose: 50 mg/day

Extended release capsules: Oral: 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 daily dose: 80 mg/day

Left ventricular dysfunction following MI: Adolescents ≥ 18 years: Note: Initiate only after patient is hemodynamically stable and fluid retention has been minimized.

Immediate release tablets: Oral: Initial: 3.125-6.25 mg twice daily; increase dosage incrementally (eg, from 6.25 to 12.5 mg twice daily) at intervals of 3-10 days, as tolerated, to a target dose of 25 mg twice daily

Extended release capsules: Oral: Initial: 10-20 mg once daily; increase dosage incrementally at intervals of 3-10 days, as tolerated, to a target dose of 80 mg once daily

Conversion from immediate release to extended release (Coreg CR®): Adolescents ≥ 18 years:

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: Renal Impairment: Pediatric

No adjustment required. Note: Mean AUCs were 40% to 50% higher in adult patients with moderate to severe renal dysfunction who received immediate release carvedilol, but the ranges of AUCs were similar to patients with normal renal function

Hemodialysis: Hemodialysis does not significantly clear carvedilol.

Dosing: Hepatic Impairment: Pediatric

Mild to moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in manufacturer’s labeling; use with caution; monitor for symptoms of drug-induced toxicity.

Severe impairment (Child-Pugh class C): Use is contraindicated as drug is extensively metabolized by the liver. Note: Adult patients with severe cirrhotic liver disease achieved carvedilol serum concentrations four- to sevenfold higher than normal patients following a single dose of immediate release carvedilol

Use: Labeled Indications

Heart failure with reduced ejection fraction (HFrEF): Mild to severe chronic heart failure of ischemic or cardiomyopathic origin.

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2017]).

Left ventricular dysfunction following MI: Left ventricular dysfunction following MI (clinically stable with LVEF ≤40%)

Use: Off-Label: Adult

  Acute MILevel of Evidence [G]

According to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of ST-elevation myocardial infarction (STEMI) and the ACC/AHA guidelines for the management of non-ST-elevation ACS (NSTE-ACS), oral beta-blockers should be initiated within the first 24 hours unless the patient has signs of heart failure, evidence of a low-output state, an increased risk for cardiogenic shock, or other contraindications. However, recommendations do not specify any particular beta-blocking agent for optimal treatment of NSTE-ACS. Thus, clinicians must use practical experience to determine proper therapy in managing patients Ref.

  Atrial fibrillation (rate control)Level of Evidence [B, G]

Data from a randomized, double-blind, placebo-controlled trial supports the use of carvedilol (with or without digoxin) in the management of atrial fibrillation in patients with heart failure Ref. Additional trials may be necessary to further define the role of carvedilol for this condition.

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation, the use of beta-blockers, including carvedilol, for ventricular rate control in patients with paroxysmal, persistent, or permanent AF is effective and recommended for this condition especially in patients with heart failure.

  Chronic stable anginaLevel of Evidence [G]

Beta-blockers are recommended (class IB evidence) by American College of Cardiology/American Heart Association (ACC/AHA) guidelines as initial therapy, in the absence of contraindications, to prevent MI and death caused by chronic stable angina in patients with prior MI. In patients without prior MI, beta-blockers, as a class, are recommended for use in chronic stable angina as class IIC evidence. Individual beta-blockers are not specified within guidelines Ref.

  Gastroesophageal variceal hemorrhage prophylaxis in patients with cirrhosisLevel of Evidence [B, G]

Current guidelines recommend the use of nonselective beta-blockers as first-line therapy for the management and prevention of gastroesophageal varices and variceal hemorrhage. To ensure maximum efficacy, the dose should be titrated to the highest level tolerated while reducing patient heart rate to no lower than 55 bpm. Although guidelines include other nonselective beta-blockers (nadolol and propranolol) in their recommendations, carvedilol is not mentioned specifically. Trials comparing carvedilol with propranolol and nadolol in the primary prevention of variceal bleed would be beneficial to determine the superiority of certain nonselective beta-blocking agents. Access Full Off-Label Monograph

  Ventricular arrhythmiasLevel of Evidence [G]

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Arrhythmias:

AHA/ACC/HRS, “2017 AHA/ACC/HRS Guideline for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death,” October 2017

AHA/ACC/HRS, “2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation,” March 2014

Canadian Cardiovascular Society, “2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation,” 2016

Heart Failure:

ACC/AHA/HFSA, “Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure,” August 2017

ACC/AHA/HFSA, “2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure,” May 2016

ACCF/AHA, “2013 ACCF/AHA Guideline for the Management of Heart Failure,” June 2013

Hypertension:

“2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults,” November 2017.

“ACCF/AHA Expert Consensus Document on Hypertension in the Elderly,” 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Canadian Cardiovascular Society, “2012 Heart Failure Management Guidelines Update: Focus on Acute and Chronic Heart Failure,” 2012

Eighth Joint National Committee (JNC 8), “2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults,” December 2013

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, “2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” July 2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

ACCF/AHA, “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction,” December 2012

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes,” September 2014

Surgery:

ACC/AHA, “2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery,” August 2014

Valvular Heart Disease:

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

Administration: Oral

Administer with food to minimize the risk of orthostatic hypotension. Extended-release capsules and its contents should not be crushed, chewed, or divided. Capsules may be opened and its contents sprinkled on applesauce for immediate use.

Administration: Pediatric

Oral:

Immediate-release tablets: Administer with food to decrease the risk of orthostatic hypotension.

Extended-release capsules: Administer with food, preferably in the morning; do not crush or chew capsule; swallow whole; do not take in divided doses. Capsule may be opened and contents sprinkled on a spoonful of applesauce; swallow applesauce/medication mixture immediately; do not chew; do not store for later use; do not use warm applesauce; do not sprinkle capsule contents on food other than applesauce; drink fluids after dose to make sure mixture is completely swallowed.

Dietary Considerations

Should be taken with food to minimize the risk of orthostatic hypotension.

Storage/Stability

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). Protect from light.

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.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience loss of strength and energy, diarrhea, headache, nausea, vomiting, weight gain, joint pain, or contact lens discomfort. Have patient report immediately to prescriber signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), severe dizziness, passing out, urinary retention, change in amount of urine passed, angina, bradycardia, or vision changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
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

Documentation of allergenic cross-reactivity for drugs alpha/beta adrenergic blocking agents is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Severe hypotension; primary obstructive valvular heart disease; mental incapacity (eg, severe Alzheimer disease, alcoholism, drug abuse), unless closely supervised by an appropriate caregiver.

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.

• Bradycardia: May occur; reduce dosage if heart rate drops to <55 beats/minute.

• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; 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. Advise patients to avoid driving or other hazardous tasks during initiation of therapy due to the risk of syncope.

Disease-related concerns:

• Angina: Use with caution in patients suspected of having Prinzmetal variant angina.

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.

• 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/or systolic BP <100 mm Hg. Initiate cautiously, titrate gradually, 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.

• 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; use with caution and monitor for progression of arterial obstruction.

• Pheochromocytoma (untreated): Use with caution; adequate alpha-blockade should be initiated 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.

• 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:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.

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. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary and prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.

• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.

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 US 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.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Adverse events, such as fetal/neonatal bradycardia, hypoglycemia, and reduced birth weight, have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth is generally recommended.

Untreated chronic maternal hypertension and preeclampsia are also associated with adverse events in the fetus, infant, and mother (ACOG 2015; Magee 2014). Although beta-blockers may be used when treatment of hypertension or heart failure in pregnancy is indicated, agents other than carvedilol are preferred (ACOG 2013; ESC [Regitz-Zagrosek 2011]; Magee 2014).

Breast-Feeding Considerations

It is not known if carvedilol is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfeeding is not recommended for women with heart failure related to peripartum cardiomyopathy due to the high metabolic demands of lactation and breastfeeding (ESC [Regitz-Zagrosek 2011]; Sliwa 2010).

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Cardiovascular: Hypotension (≤20%), orthostatic hypotension (≤20%)

Central nervous system: Dizziness (2% to 32%), fatigue (24%)

Endocrine & metabolic: Weight gain (10% to 12%), hyperglycemia (5% to 12%)

Gastrointestinal: Diarrhea (1% to 12%)

Neuromuscular & skeletal: Asthenia (11%)

1% to 10%:

Cardiovascular: Bradycardia (≤10%), syncope (≤8%), peripheral edema (1% to 7%), angina pectoris (6%), edema (5% to 6%), atrioventricular block (>1% to ≤3%), cerebrovascular accident (>1% to ≤3%), exacerbation of angina pectoris (>1% to ≤3%), hypertension (>1% to ≤3%), lower extremity edema (>1% to ≤3%), palpitations (>1% to ≤3%), peripheral vascular disease (>1% to ≤3%), peripheral ischemia (≤1%), tachycardia (≤1%)

Central nervous system: Headache (5% to 8%), depression (>1% to ≤3%), drowsiness (>1% to ≤3%), hypoesthesia (>1% to ≤3%), hypotonia (>1% to ≤3%), malaise (>1% to ≤3%), vertigo (>1% to ≤3%), paresthesia (1% to ≤3%), insomnia (1% to 2%), abnormality in thinking (≤1%), emotional lability (≤1%), exacerbation of depression (≤1%), lack of concentration (≤1%), nervousness (≤1%), nightmares (≤1%), sleep disorder (≤1%)

Dermatologic: Diaphoresis (≤1%), erythematous rash (≤1%), maculopapular rash (≤1%), pruritus (≤1%), psoriasiform eruption (≤1%), skin photosensitivity (≤1%)

Endocrine & metabolic: Increased nonprotein nitrogen (6%), dependent edema (4%), hypercholesterolemia (4%), albuminuria (>1% to ≤3%), diabetes mellitus (>1% to ≤3%), glycosuria (>1% to ≤3%), gout (>1% to ≤3%), hyperkalemia (>1% to ≤3%), hyperuricemia (>1% to ≤3%), hypervolemia (>1% to ≤3%), hypoglycemia (>1% to ≤3%), hyponatremia (>1% to ≤3%), hypovolemia (>1% to ≤3%), impotence (>1% to ≤3%), increased gamma-glutamyl transferase (>1% to ≤3%), weight loss (>1% to ≤3%), decreased libido (≤1%), hypertriglyceridemia (≤1%), hypokalemia (≤1%)

Gastrointestinal: Nausea (2% to 9%), vomiting (6%), melena (>1% to ≤3%), periodontitis (>1% to ≤3%), gastrointestinal pain (1% to ≤3%), xerostomia (≤1%)

Genitourinary: Hematuria (>1% to ≤3%), urinary frequency (≤1%)

Hematologic & oncologic: Hypoprothrombinemia (>1% to ≤3%), nonthrombocytopenic purpura (>1% to ≤3%), thrombocytopenia (1% to ≤3%), leukopenia (≤1%)

Hepatic: Increased serum alanine aminotransferase (>1% to ≤3%), increased serum alkaline phosphatase (>1% to ≤3%), increased serum aspartate aminotransferase (>1% to ≤3%), hyperbilirubinemia (≤1%), increased liver enzymes (≤1%)

Hypersensitivity: Hypersensitivity reaction (>1% to ≤3%)

Neuromuscular & skeletal: Arthralgia (6%), arthritis (>1% to ≤3%), muscle cramps (>1% to ≤3%), hypokinesia (≤1%)

Ophthalmic: Visual disturbance (5%), blurred vision (>1% to ≤3%)

Otic: Tinnitus (≤1%)

Renal: Increased blood urea nitrogen (≤6%), increased serum creatinine (>1% to ≤3%), renal insufficiency (>1% to ≤3%)

Respiratory: Increased cough (5%), nasopharyngitis (4%), rales (4%), dyspnea (>3%), flu-like symptoms (>1% to ≤3%), nasal congestion (1%), paranasal sinus congestion (1%), asthma (≤1%)

Miscellaneous: Fever (>1% to ≤3%)

Frequency not defined:

Hematologic & oncologic: Anemia

Respiratory: Pulmonary edema

<1%, postmarketing, and/or case reports: Abnormal lymphocytes, alopecia, anaphylactoid shock, anaphylaxis, angioedema, aplastic anemia, amnesia, auditory impairment, bronchospasm, bundle branch block, cerebrovascular disease, complete atrioventricular block, decreased HDL cholesterol, erythema multiforme, exfoliative dermatitis, gastrointestinal hemorrhage, interstitial pneumonitis, ischemic heart disease, migraine, neuralgia, pancytopenia, paresis, respiratory alkalosis, seizure, Stevens-Johnson syndrome, toxic epidermal necrolysis, urinary incontinence

Allergy and Idiosyncratic Reactions
Toxicology
Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C9 (minor), CYP2D6 (major), CYP2E1 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1; Note:Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein/ABCB1

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Risk D: Consider therapy modification

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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 C: Monitor therapy

Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable.Exceptions: Apraclonidine. Risk D: Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot 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

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. 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

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).Risk C: Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Risk D: Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Risk D: Consider therapy modification

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. 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. Risk C: Monitor therapy

Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Risk D: Consider therapy modification

Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Carvedilol. Risk C: Monitor therapy

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Colchicine: P-glycoprotein/ABCB1 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. See full monograph for details. 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

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Digoxin: May enhance the bradycardic effect of Carvedilol. 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. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D: Consider therapy modification

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

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Risk D: Consider therapy modification

EPINEPHrine (Nasal): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Epinephrine (Racemic): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of Epinephrine (Racemic). Risk C: Monitor therapy

EPINEPHrine (Systemic): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy

Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Risk D: Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy

Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Risk D: Consider therapy modification

Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Risk X: Avoid combination

Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Risk D: Consider therapy modification

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Insulins: Beta-Blockers may enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Risk C: Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy

NiCARdipine: May enhance the hypotensive effect of Carvedilol. NiCARdipine may precipitate signs of heart failure in susceptible patients on Carvedilol NiCARdipine may increase the serum concentration of Carvedilol. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 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/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 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/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 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.).Exceptions: Loperamide. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Risk C: Monitor therapy

Regorafenib: May enhance the bradycardic effect 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

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Risk C: Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. 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

Talazoparib: Carvedilol may increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. After a period of 3 to 5 times the half-life of carvedilol, increase the talazoparib dose to the dose used before initiation of carvedilol. Risk D: Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk D: Consider therapy modification

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Food Interactions

Food decreases rate but not extent of absorption. Management: Administration with food minimizes risks of orthostatic hypotension.

Test Interactions

May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016).

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; blood glucose in diabetics; in patients with increased risk for developing renal dysfunction, monitor during dosage titration.

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable.

Advanced Practitioners 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).

Nursing Physical Assessment/Monitoring

Take blood pressure and heart rate prior to and following first dose and with any change in dosage. Caution patients with diabetes to monitor glucose levels closely (beta-blockers may alter glucose tolerance).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as phosphate:

Coreg CR: 10 mg, 20 mg, 40 mg, 80 mg

Generic: 10 mg, 20 mg, 40 mg, 80 mg

Tablet, Oral:

Coreg: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg

Generic: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • C07AG02
Generic Available (US)

Yes

Pricing: US

Capsule ER 24 Hour Therapy Pack (Carvedilol Phosphate ER Oral)

10 mg (per each): $9.91 – $10.32

20 mg (per each): $9.91 – $10.32

40 mg (per each): $9.91 – $10.32

80 mg (per each): $9.91 – $10.32

Capsule ER 24 Hour Therapy Pack (Coreg CR Oral)

10 mg (per each): $11.01

20 mg (per each): $11.01

40 mg (per each): $11.01

80 mg (per each): $11.01

Tablets (Carvedilol Oral)

3.125 mg (per each): $0.03 – $2.14

6.25 mg (per each): $0.03 – $2.14

12.5 mg (per each): $0.03 – $2.14

25 mg (per each): $0.03 – $2.14

Tablets (Coreg Oral)

3.125 mg (per each): $5.93

6.25 mg (per each): $5.93

12.5 mg (per each): $5.93

25 mg (per each): $5.93

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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 atrial pressure (RAP).

Pharmacodynamics/Kinetics

Onset of action: Antihypertensive effect: Alpha-blockade: Within 30 minutes; Beta-blockade: Within 1 hour

Peak antihypertensive effect: ~1 to 2 hours

Absorption: Oral: Rapid and extensive, but with large first pass effect; first pass effect is stereoselective with R(+) enantiomer achieving plasma concentrations 2 to 3 times higher than S(-) enantiomer; delayed with food

Distribution: Vd: 115 L; distributes into extravascular tissues

Protein binding: >98%, primarily to albumin

Metabolism: Extensively (98%) hepatic, via CYP2C9, 2D6, 3A4, 2C19, 1A2, and 2E1 (2% excreted unchanged); metabolized predominantly by aromatic ring oxidation and glucuronidation; oxidative metabolites undergo conjugation via glucuronidation and sulfation; three active metabolites (4-hydroxyphenyl metabolite is 13 times more potent than parent drug for beta-blockade, however, active metabolites achieve plasma concentrations of only 1/10 of those for carvedilol); first-pass effect; plasma concentrations in the elderly and those with cirrhotic liver disease are 50% and 4 to 7 times higher, respectively. Metabolism is subject to genetic polymorphism; CYP2D6 poor metabolizers have a 2- to 3-fold higher plasma concentration of the R(+) enantiomer and a 20% to 25% increase in the S(-) enantiomer compared to extensive metabolizers.

Bioavailability: Immediate release: ~25% to 35% (due to significant first-pass metabolism); Extended release: ~85% of immediate release; high-fat meal increases AUC and Cmax ~20%; bioavailability is increased in patients with CHF

Half-life elimination:

Infants and Children 6 weeks to 3.5 years (n=8): 2.2 hours (Laer 2002)

Children and Adolescents 5.5 to 19 years (n=7): 3.6 hours (Laer 2002)

Adults 7 to 10 hours; some have reported lower values: Adults 24 to 37 years (n=9): 5.2 hours (Laer 2002)

R(+)-carvedilol: 5 to 9 hours

S(-)-carvedilol: 7 to 11 hours

Time to peak, plasma: Extended release: ~5 hours

Excretion: Primarily feces; urine (<2%, unchanged)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Plasma concentrations may be higher (40% to 50% in moderate to severe renal impairment).

Hepatic function impairment: Severe hepatic impairment (cirrhosis) patients have a 4- to 7-fold increase in concentrations.

Geriatric: Plasma levels are about 50% higher.

Heart failure: AUC and Cmax increased up to 100%.

Local Anesthetic/Vasoconstrictor Precautions

Carvedilol is a nonselective beta-blocker, but also has alpha-adrenergic blocking actions. No intrinsic sympathomimetic activity has been documented for carvedilol. Unlike other nonselective beta-blockers such as propranolol, with which epinephrine has interacted with to result in initial hypertensive episode followed by tachycardia, any interaction with carvedilol and vasoconstrictor to result in hypertensive episode would not be expected. There is no information available to require special precautions.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment. 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.

Effects on Bleeding

No information available to require special precautions

FDA Approval Date
September 14, 1995
References

ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Chronic Hypertension in Pregnancy. ACOG Committee on Practice Bulletins. Obstet Gynecol. 2001;98(suppl 1):177-185.[PubMed 11508256]

Alade SL, Brown RE, Paquet A. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597.[PubMed 3960626]

Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society [published online ahead of print October 30, 2017]. Circulation. 2017. doi: 10.1161/CIR.0000000000000549.[PubMed 29084731]

American College of Obstetricians and Gynecologists (ACOG), Committee on Obstetric Practice. Committee Opinion No. 623: emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol. 2015;125(2):521-525.[PubMed 25611642]

American College of Obstetricians and Gynecologists (ACOG), Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.[PubMed 24150027 ]

Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017.[PubMed 25260718]

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, 123(21):2434-506.[PubMed 21518977]

Baiges A, Hernández-Gea V, Bosch J. Pharmacologic prevention of variceal bleeding and rebleeding. Hepatol Int. 2018;12(Suppl 1):S68-S80. doi: 10.1007/s12072-017-9833-y.[PubMed 29210030]

Bhardwaj A, Kedarisetty CK, Vashishtha C, et al. Carvedilol delays the progression of small oesophageal varices in patients with cirrhosis: a randomised placebo-controlled trial. Gut. 2017;66(10):1838-1843. doi: 10.1136/gutjnl-2016-311735.[PubMed 27298379]

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.[PubMed 18410416]

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.[PubMed 8941106]

Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm[PubMed 6423951]

Colucci WS, Packer M, Bristow MR, et al, “Carvedilol Inhibits Clinical Progression in Patients With Mild Symptoms of Heart Failure. US Carvedilol Heart Failure Study Group,” Circulation, 1996, 94(11):2800-6.[PubMed 8941105]

Colucci WS. Use of beta blockers in heart failure with reduced ejection fraction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 6, 2018.

Coreg (carvedilol immediate release) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; September 2017.

Coreg CR (carvedilol extended release) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; September 2017.

Dahlof B, Devereux RB, Kjeldsen SE, et al; Life Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995-1003.[PubMed 11937178]

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.[PubMed 11356434]

Fihn SD, Gardin JM, Abrams J, et al, “2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons,” Circulation, 2012, 126(25):3097-137.[PubMed 23166211]

Foster CA and Aston SJ, “Propranolol-Epinephrine Interaction: A Potential Disaster,” Plast Reconstr Surg, 1983, 72(1):74-8.[PubMed 6867180 ]

Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: 10.1210/jc.2015-4061.[PubMed 26934393]

Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017;65(1):310-335. doi: 10.1002/hep.28906.[PubMed 27786365]

Gibbons RJ, Abrams J, Chatterjee K, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines Committee on the Management of Patients With Chronic Stable Angina. 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). Circulation. 2003;107(1):149-158.[PubMed 12515758]

Go AS, Bauman M, King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention [published online November 15, 2013]. Hypertension.[PubMed 24243703]

Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313.[PubMed 12534540]

James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.[PubMed 24352797]

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online March 28, 2014]. Circulation.[PubMed 24682347]

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.[PubMed 16793810]

Khand AU, Rankin AC, Martin W, Taylor J, Gemmell I, Cleland JG. Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? J Am Coll Cardiol. 2003;42(11):1944-1951.[PubMed 14662257]

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;289(6):712-718.[PubMed 12585949]

Labrecque D, Dite P, Fried M, et al; World Gastroenterology Organisation. World Gastroenterology Organisation practice guideline: esophageal varices. http://www.worldgastroenterology.org/UserFiles/file/guidelines/esophageal-varices-english-2014.pdf. Published January 2014. Accessed September 20, 2016

Laer S, Mir TS, Behn F, et al, “Carvedilol Therapy in Pediatric Patients With Congestive Heart Failure: A Study Investigating Clinical and Pharmacokinetic Parameters,” Am Heart J, 2002, 143(5):916-22.[PubMed 12040358]

Lang DM, “Anaphylactoid and Anaphylactic Reactions. Hazards of Beta-Blockers,” Drug Saf, 1995, 12(5):299-304.[PubMed 7669259]

Lennestål R, Otterblad Olausson P, Källén B. Maternal Use of Antihypertensive Drugs in Early Pregnancy and Delivery Outcome, Notably the Presence of Congenital Heart Defects in the Infants. Eur J Clin Pharmacol. 2009;65(6):615-625.[PubMed 19198819]

Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172.[PubMed 10985636]

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.[PubMed 10091817]

Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P, Canadian Hypertensive Disorders of Pregnancy Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obstet Gynaecol Can. 2014;36(5):416-441.[PubMed 24927294 ]

Nishimura RA, Otto CM, Bonow RO, et al, 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-92. doi: 10.1161/CIR.0000000000000029.[PubMed 24589852]

O’Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2013;128(25):e481]. Circulation. 2013;127(4):e362-e425. doi: 10.1161/CIR.0b013e3182742cf6.[PubMed 23247304]

Packer M, Bristow MR, Cohn JN, et al; US Carvedilol Heart Failure Study Group. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med.1996a;334(21):1349-1355.[PubMed 8614419]

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):1651-1658.[PubMed 11386263]

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. 1996b;94(11):2793-2799.[PubMed 8941104]

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.[PubMed 18479744]

“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.[PubMed 9033462]

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.[PubMed 16210252]

Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(24):3147-3197.[PubMed 21873418]

Reiberger T, Ulbrich G, Ferlitsch A, et al; Vienna Hepatic Hemodynamic Lab. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut. 2013;62(11):1634-1641.[PubMed 23250049]

Sanyal AJ. Primary and pre-primary prophylaxis against variceal hemorrhage in patients with cirrhosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 6, 2018.

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Sinagra E, Perricone G, D’Amico M, Tinè F, D’Amico G. Systematic review with meta-analysis: the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis. Aliment Pharmacol Ther. 2014;39(6):557-568. doi: 10.1111/apt.12634.[PubMed 24461301]

Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail. 2010;12(8):767-778.[PubMed 20675664 ]

Tripathi D, Ferguson JW, Kochar N, et al. Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology. 2009;50(3):825-833.[PubMed 19610055]

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Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online ahead of print on November 13, 2017]. Hypertension. 2017. doi: 10.1161/HYP.0000000000000065.[PubMed 29133356]

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Brand Names: International

Alvelol (KR); Arlec (TR); Artist (JP); Avernol (ET, MT, TR); Avidol (BD); Betacard (PH); Betaplex (CL); Bicol (TR); Bloquedil (CR, DO, GT, HN, NI, PA, SV); Blorec (ID); Cadil (HR); Caraca-12.5 (ZW); Caraten (TH); Carbloxal (ID); Carca-3 (ZW); Carca-6 (ZW); Cardilol (EG, JO, PH); Cardine (SY); Cardiol (FI, MY); Cardiostad (UA); Cardipres (PH); Cardivas (IN, VN); Cardoz (LK, TZ); Cargen (KR); Carloc (ZA); Carlov (PK); Carsantin (VN); Carved (BD); Carvedexxon (IL); Carvedil (EC); Carvediteg (CR, GT, HN, NI, PA, SV); Carvedlol (KR); Carvelmed (VN); Carvelol (KR, NZ); Carvena (EG); Carvepen (SG); Carveta (KR); Carvetrend (UA); Carvid (PH); Carvidex (MT, TR, UA); Carvidil (RU); Carviditeg (DO); Carvidol (CN, ET, JO, SA); Carvil (LK); Carvilar (DO); Carvo (TW); Cavel (MY); Coreg (BB, BM, BR, BS, BZ, GY, JM, SR, TT); Coritensil (AR); Coronis (ET); Coropres (ES); Corubin (EC); Coryol (CO, CR, GT, NI, PA, RO, SV); Dicarz (AU); Dilabloc (PH); Dilapress (LK); Dilatrend (AE, AR, AT, AU, BF, BG, BH, BJ, CH, CI, CL, CN, CY, CZ, DE, EC, EE, EG, ET, GH, GM, GN, GR, HK, HR, HU, IT, JO, KE, KR, KW, LB, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NO, NZ, PE, PH, PL, PY, QA, RO, SA, SC, SD, SG, SL, SN, TH, TN, TR, TW, TZ, UG, UY, VE, VN, ZM, ZW); Dilatrend SR (KR); Dilbloc (PT); Dilgard (BD); Dimitone (DK); Duobloc (PH); Epicarve (EG); Eucardic (GB, NL); Gladycor (MT); Glovedol (PH); Ictus (BR); Karter (KR); Karvedil (BD); Karvex (EG); Karvil (ET, PH, ZW); Kredex (AU, BE, FR, LU, SE); Longcardio (TW); Normotride (ES); Querto (DE); Riacavilol (SA); Scodilol (VN); Syntrend (TW); Talliton (BB, BM, BS, BZ, GY, HK, JM, SR, TT, UA, VN); Tocarlol (TH); Udilol (TW); V-Bloc (ID); Vasodilren (KR); Vedilol (AU, KR); Volirop (AU); Xetin (PY); Xicard (PH); Ziclar (PY)

Carvedilol (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(KAR ve dil ole)

Brand Names: US

Coreg; Coreg CR

Brand Names: Canada

Apo-Carvedilol; Auro-Carvedilol; Dom-Carvedilol; JAMP-Carvedilol; Mylan-Carvedilol; Novo-Carvedilol; PMS-Carvedilol; RAN-Carvedilol; ratio-Carvedilol

What is this drug used for?
  • It is used to treat heart failure (weak heart).
  • It is used to treat high blood pressure.
  • It is used to help heart function after a heart attack.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to carvedilol or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Asthma, other lung or breathing problems that cause shortness of breath or wheezing, certain types of abnormal heartbeats called heart block or sick sinus syndrome, a slow heartbeat, or heart failure that is being treated with certain IV drugs.
  • If you have liver disease.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • This drug may hide the signs of low blood sugar. Talk with the doctor.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • Do not stop taking this drug all of a sudden. If you do, chest pain that is worse and in some cases heart attack may occur. The risk may be greater if you have certain types of heart disease. To avoid side effects, you will want to slowly stop this drug as ordered by your doctor. Call your doctor right away if you have new or worse chest pain or if other heart problems occur.
  • This drug may make it harder to tell if you have signs of an overactive thyroid like fast heartbeat. If you have an overactive thyroid and stop taking this drug all of a sudden, it may get worse and could be life-threatening. Talk with your doctor.
  • If you have had a very bad allergic reaction, talk with your doctor. You may have a chance of an even worse reaction if you come into contact with what caused your allergy. If you use epinephrine to treat very bad allergic reactions, talk with your doctor. Epinephrine may not work as well while you are taking this drug.
  • If you are having cataract surgery or other eye procedure, talk with your doctor.
  • If you wear contact lenses, you may have fewer tears or dry eyes. Call your doctor if this bothers you.
  • If you are taking this drug and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • This drug may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this drug with your other drugs.
  • This drug is not approved for use in children younger than 18 years of age. Talk with the doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Very bad dizziness or passing out.
  • Not able to pass urine or change in how much urine is passed.
  • Chest pain that is new or worse.
  • Slow heartbeat.
  • Change in eyesight.
  • Call your doctor right away if you have shortness of breath, a big weight gain, a heartbeat that is not normal, or swelling in the arms or legs that is new or worse. Worsening of heart failure has happened with this drug.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dizziness.
  • Feeling tired or weak.
  • Diarrhea.
  • Headache.
  • Upset stomach or throwing up.
  • Weight gain.
  • Joint pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Take this drug at the same time of day.
  • To gain the most benefit, do not miss doses.
  • Take this drug with food.
  • Long-acting capsules:
  • Swallow whole. Do not chew, break, or crush.
  • If you cannot swallow this drug whole, you may sprinkle the contents on applesauce. If you do this, swallow the mixture right away without chewing.
  • If mixing on applesauce, the applesauce should not be warm. Do not sprinkle on other liquids or foods.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Carvedilol (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(KAR ve dil ole)

Brand Names: US

Coreg; Coreg CR

Brand Names: Canada

Apo-Carvedilol; Auro-Carvedilol; Dom-Carvedilol; JAMP-Carvedilol; Mylan-Carvedilol; Novo-Carvedilol; PMS-Carvedilol; RAN-Carvedilol; ratio-Carvedilol

What is this drug used for?
  • It is used to treat heart failure (weak heart).
  • It is used to treat high blood pressure.
  • It is used to help heart function after a heart attack.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has any of these health problems: Asthma, other lung or breathing problems that cause shortness of breath or wheezing, certain types of abnormal heartbeats called heart block or sick sinus syndrome, a slow heartbeat, or heart failure that is being treated with certain IV drugs.
  • If your child has liver disease.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child’s blood pressure and heart rate checked often. Talk with your child’s doctor.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • This drug may hide the signs of low blood sugar. Talk with the doctor.
  • If your child has high blood sugar (diabetes), you will need to watch his/her blood sugar closely.
  • Do not stop giving this drug to your child all of a sudden. If you do, chest pain that is worse and in some cases heart attack may occur. The chance may be higher if your child has certain types of heart disease. To avoid side effects, you will want to slowly stop this drug as ordered by the doctor. Call the doctor right away if your child has new or worse chest pain or if other heart problems happen.
  • This drug may make it harder to tell if your child has signs of an overactive thyroid like fast heartbeat. If your child has an overactive thyroid and stops taking this drug all of a sudden, it may get worse and could be life-threatening. Talk with the doctor.
  • If your child has had a very bad allergic reaction, talk with the doctor. Your child may have a chance of an even worse reaction if your child comes into contact with what caused the allergy. If your child uses epinephrine to treat very bad allergic reactions, talk with the doctor. Epinephrine may not work as well while your child is taking this drug.
  • If your child is having cataract surgery, talk with the doctor.
  • If your child wears contact lenses, your child may have fewer tears or dry eyes. Call the doctor if this bothers your child.
  • If your child is taking this drug and has high blood pressure, talk with the doctor before giving OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • This drug may affect how much of some other drugs are in the body. If your child is taking other drugs, talk with the doctor. Your child may need to have blood work checked more closely while taking this drug with other drugs.
  • This drug is not approved for use in children younger than 18 years of age. Talk with the doctor.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Very bad dizziness or passing out.
  • Not able to pass urine or change in how much urine is passed.
  • Chest pain that is new or worse.
  • Slow heartbeat.
  • Change in eyesight.
  • Call your child’s doctor right away if your child has shortness of breath, a big weight gain, a heartbeat that is not normal, or swelling in the arms or legs that is new or worse. Worsening of heart failure has happened with this drug.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Dizziness.
  • Feeling tired or weak.
  • Diarrhea.
  • Headache.
  • Upset stomach or throwing up.
  • Weight gain.
  • Joint pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Give this drug at the same time of day.
  • To gain the most benefit, do not miss giving your child doses.
  • Give this drug with food.
  • Long-acting capsules:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • If your child cannot swallow this drug whole, you may sprinkle the contents on applesauce. If you do this, have your child swallow the mixture right away without chewing.
  • If mixing on applesauce, the applesauce should not be warm. Do not sprinkle on other liquids or foods.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not put on 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.