Version May 2024
Angina, chronic stable (off-label use):
Note: For vasospastic angina, beta-blockers are not recommended; other agents (eg, calcium channel blockers, nitrates) are preferred. For nonvasospastic angina, guidelines recommend titrating dose to a resting heart rate of 55 to 60 beats per minute (Ref), while other experts recommend a target of 60 to 70 beats per minute (Ref).
Immediate release: Oral: Initial: 12.5 mg twice daily; increase dose as tolerated to desired effect; usual dosage range: 25 to 50 mg twice daily (Ref).
Atrial fibrillation/flutter, maintenance of ventricular rate control (off-label use):
Note: Initiate cautiously in patients with concomitant heart failure. Avoid initiating or up-titrating therapy in patients with decompensated heart failure; for unstable patients, electrical cardioversion is preferred (Ref).
Immediate release: Oral: Initial: 3.125 mg twice daily; increase dose as tolerated to achieve ventricular rate control up to 25 mg twice daily (Ref).
Heart failure with reduced ejection fraction :
Note: Initiate only in stable, euvolemic patients. In hospitalized patients, volume status should be optimized and IV diuretics, IV vasodilators, and IV inotropic agents successfully discontinued prior to initiating therapy. Use caution when initiating in patients with New York Heart Association class IV symptoms or recent heart failure exacerbation (particularly if inotropes were required during hospital course) (Ref).
Immediate release: Oral: Initial: 3.125 mg twice daily; up-titrate gradually (eg, doubling the dose every ≥ 1 to 2 weeks) to the target dose while monitoring for signs and symptoms of heart failure (Ref).
Target dose:
≤85 kg: 25 mg twice daily.
>85 kg: 50 mg twice daily.
Extended release: Oral: Initial: 10 mg once daily; up-titrate gradually (eg, doubling the dose every 1 to 2 weeks) to the target dose of 80 mg once daily while monitoring for signs and symptoms of heart failure (Ref).
Hypertension (alternative agent):
Note: Not recommended in the absence of specific comorbidities (eg, arrhythmia ischemic heart disease, heart failure with reduced ejection fraction) (Ref).
Immediate release: Oral: Initial: 6.25 mg twice daily; titrate in ≥1-week intervals as needed based on patient response; usual dosage range: 6.25 to 25 mg twice daily; maximum dose: 50 mg/day (Ref).
Extended release: Oral: Initial: 20 mg once daily; titrate in ≥1-week intervals as needed based on patient response; usual dosage range: 20 to 80 mg/day; maximum dose: 80 mg/day (Ref).
Myocardial infarction, early treatment and secondary prevention (alternative agent) (off-label use):
Note: An oral beta-blocker is recommended within the first 24 hours for most patients. Patients who do not receive a beta-blocker within 24 hours of myocardial infarction due to contraindications should be reevaluated for secondary prevention at a later date (Ref).
Immediate release: Oral: Initial: 3.125 to 6.25 mg twice daily; titrate dose based on heart rate and blood pressure as tolerated up to 25 mg twice daily (Ref). The optimal duration of therapy is unknown; treat for a minimum of 3 years (Ref).
Nonsustained ventricular tachycardia or ventricular premature beats, symptomatic (off-label use) :
Immediate release: Oral: Initial: 3.125 mg twice daily; titrate as needed based on response and tolerability up to 25 mg twice daily (Ref).
Variceal hemorrhage prophylaxis, primary (alternative agent) (off-label use):
Immediate release: Oral: Initial: 3.125 mg twice daily or 6.25 mg once daily; titrate according to resting heart rate (target 55 to 60 beats per minute) while maintaining blood pressure (eg, systolic blood pressure ≥90 mm Hg) to a maximum dose of 6.25 mg twice daily (Ref).
Conversion from immediate release to extended release (Coreg CR):
Current dose IR tablets 3.125 mg twice daily: Convert to ER capsules 10 mg once daily.
Current dose IR tablets 6.25 mg twice daily: Convert to ER capsules 20 mg once daily.
Current dose IR tablets 12.5 mg twice daily: Convert to ER capsules 40 mg once daily.
Current dose IR tablets 25 mg twice daily: Convert to ER capsules 80 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (Ref); no supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (Ref); no dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; dose conservatively and interrupt therapy in the setting of hypotension (eg, mean arterial pressure [MAP] <65 mm Hg), acute kidney injury, or hyponatremia (Ref).
Severe impairment: Use is contraindicated per manufacturer; however, experts will use if indicated (eg, for variceal hemorrhage prophylaxis); dose conservatively and interrupt therapy in the setting of hypotension (eg, MAP <65 mm Hg), acute kidney injury, or hyponatremia (Ref).
Refer to adult dosing. Consider lower initial doses and titrate to response (Ref).
(For additional information see "Carvedilol: Pediatric drug information")
Dosage guidance:
Dosing: Individualize dosage for each patient; monitor patients closely during initiation and upwards titration of dose; reduce dose for hypotension or bradycardia. Pharmacokinetic data suggest a faster carvedilol elimination in young pediatric patients (<3.5 years of age), which may require more frequent dosing (3 times daily) and a higher target dose per kg (Ref).
Heart failure: Note: Prior to initiating therapy, other congestive heart failure medications should be stabilized and fluid retention minimized.
Infants, Children, and Adolescents: Limited data available, reported regimens and efficacy results variable; optimal dose not established:
Immediate release: Oral: Initial: 0.04 to 0.075 mg/kg/dose twice daily titrate as tolerated; may increase dose by 50% to 100% every 2 weeks; maximum daily dose: 1 mg/kg/day up to 50 mg/day (Ref). Dosing based on 2 retrospective analyses and 1 prospective, randomized-controlled study (n=110, age range: 3 months to 19 years) which showed improvement in left ventricular function and heart failure symptoms. However, a large, multicenter, double-blind, placebo-controlled, dose-finding trial was not able to show statistical difference in treatment effect compared to placebo; of note, a subset analysis suggested ventricular morphology may play a role in the efficacy of carvedilol in the treatment of heart failure (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; in adults, no adjustment is necessary (Ref).
Hemodialysis: Hemodialysis does not appear to significantly clear carvedilol.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling. In adults, use is contraindicated.
Beta-blockers may cause first-degree atrioventricular (AV) block, second-degree AV block, or complete atrioventricular block (Ref). At maintenance dosing, second- or third-degree AV block are less likely (Ref). Beta-blocking agents with intrinsic sympathomimetic activity (eg, pindolol) may cause fewer AV conduction abnormalities than those without intrinsic sympathomimetic activity (eg, carvedilol) due to their partial agonist effects (Ref). In most cases (up to 72%), AV block associated with a beta-blocker will resolve upon discontinuation; however, there are reported cases of recurrent AV block and nearly 50% of patients with more severe AV block may require a permanent pacemaker (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Blockade of cardiac beta-1 adrenergic receptors results in slowed conduction and prolongation of the refractory period of the AV node. Slowing of AV conduction can lead to AV block (Ref).
Onset: Varied; one study included patients who were on a beta-blocker for more than 1 month (Ref); however, other studies noted prolongation of the PR interval or AV nodal refractory period occurring anywhere from 1 dose to several days following treatment initiation (Ref).
Risk factors:
• Impaired AV node conduction or sinus node function (Ref)
• Concurrent use of other agents that impair AV nodal conduction (eg, nondihydropyridine calcium channel blockers, digoxin, ivabradine, select antiarrhythmic agents) (Ref)
• Older patients (Ref)
Nonselective beta-blockers (eg, carvedilol) have a higher risk of bronchospasm compared to cardioselective beta-blockers (Ref) and may lead to drug discontinuation in patients with chronic obstructive pulmonary diseases (COPD) or asthma (Ref). One study showed that patients with asthma and heart failure tolerated carvedilol poorly (Ref). Concurrent use of inhaled bronchodilators and/or corticosteroids are protective against beta-blocker–induced bronchospasm in patients with COPD or asthma (Ref). Bronchospasm is reversible upon discontinuation (Ref).
Mechanism: Dose-related; related to pharmacologic action. Beta-blocking agents can lead to airway smooth muscle constriction by antagonism of beta-2 receptors (Ref).
Onset: Varied; changes in peak expiratory flow rates have occurred after 1 dose. Discontinuation due to carvedilol-induced bronchospasm varied from 5 days to 6 months (Ref).
Risk factors:
• Reactive airway disease (asthma) (Ref)
Beta-blockers may cause CNS effects such as fatigue, sleep disorder, insomnia, and vivid dreams (Ref). Memory impairment has been reported with carvedilol; however, newer data suggest it may be helpful for patients with Alzheimer disease (Ref). Sexual disorders may occur; however, patients who require beta-blocker therapy have risk factors for erectile dysfunction (eg, coronary artery disease, heart failure) (Ref). Lipophilic beta-blockers (such as carvedilol, which is highly lipophilic) penetrate the blood-brain barrier to a greater extent than hydrophilic beta-blockers, possibly leading to a greater incidence of CNS effects; however, other studies have refuted this theory (Ref). CNS effects generally resolve with dose reduction or discontinuation (Ref).
Mechanism: Dose-related; exact mechanism is not fully understood. Proposed mechanisms include presence of beta receptors in the brain, affinity (and in some instances, inhibition) of beta-blocking agents towards serotonin (5-HT) receptors in the brain (affecting mood and sleep), and beta-blocker–induced decreases in central sympathetic output (Ref). Beta-1 blockade may also impact sleep by blocking sympathetic signaling to the pineal gland, resulting in suppression of nighttime levels of melatonin (Ref). Beta-blockers may cause erectile dysfunction through decreased sympathetic nervous system output and subsequent decreases in luteinizing hormone secretion and testosterone stimulation (Ref).
Onset: Intermediate; CNS effects often occur within the first few weeks of treatment (Ref).
Risk factors:
• Higher starting doses (Ref)
• Older patients (Ref)
Beta-blockers may worsen, prolong, or cause hypoglycemia (Ref). Additionally, beta-blockers may mask symptoms of hypoglycemia (tremor, irritability, palpitations), making diaphoresis the only symptom unaffected by beta-blockers (Ref). It is unclear if nonselective or selective beta-blockers are more likely to cause hypoglycemia, as data are conflicting (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Beta-blockers inhibit hepatic gluconeogenesis and glycogenolysis (Ref). Beta-blockers also reduce activation of the sympathetic nervous system, therefore masking hypoglycemic symptoms that are catecholamine-mediated (Ref).
Onset: Varied; hypoglycemia (<70 mg/dL) was reported significantly more after 24 hours of carvedilol use compared to patients not on beta-blockers (Ref). In another study, episodes of severe hypoglycemia (<50 mg/dL) were reported over the course of 4 years (Ref).
Risk factors:
• Insulin-dependent diabetes (Ref)
• Type 2 diabetes mellitus (Ref)
• Patients who are hospitalized and not requiring basal insulin (Ref)
Beta-blocker therapy should not be withdrawn abruptly but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia in patients with underlying cardiovascular disease (Ref). Some studies have found an increase in propensity-adjusted mortality and cardiovascular events; however, one study did not find changes in infarct size and left ventricular function when beta-blocker was abruptly withdrawn in patients with myocardial infarction (Ref).
Mechanism: Dose-dependent; related to the pharmacologic action. Beta blockade causes upregulation of beta receptors, enhanced receptor sensitivity, and decreased sympathetic nervous system response. Abrupt withdrawal leads to a transient sympathetic hyper-response (Ref). Another proposed mechanism involves increased platelet aggregability to epinephrine and thrombin (Ref).
Onset: Rapid/varied and transient; increases in heart rate and blood pressure appear 24 hours after abrupt withdrawal, peak after 48 hours, and subside after 7 days (Ref). In other nonselective beta-blockers (propranolol), anginal symptoms are reported to begin 12 to 24 hours after discontinuation. Development of adverse reactions is also reported to occur 1 to 21 days after withdrawal (Ref).
Risk factors:
• Abrupt withdrawal in chronic users (Lederballe Pederson 1979)
• Past medical history of coronary artery disease (including chronic stable angina) (Ref)
• Past medical history of hypertension (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults administered immediate release (IR), unless otherwise noted as extended release (ER).
>10%:
Cardiovascular: Hypotension (≤20%), orthostatic hypotension (≤20%)
Endocrine & metabolic: Hyperglycemia (5% to 12%), weight gain (10% to 12%)
Gastrointestinal: Diarrhea (IR: 2% to 12%; ER: 1%)
Nervous system: Asthenia (11%), dizziness (IR: 6% to 32%; ER: 2%), fatigue (24%) (table 1)
|
Drug (Carvedilol) |
Placebo |
Dosage Form |
Indication |
Number of Patients (Carvedilol) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
24% |
22% |
Immediate-release tablets |
Mild to moderate heart failure |
765 |
437 |
1% to 10%:
Cardiovascular: Angina pectoris (6%), atrioventricular block (1% to 3%; complete atrioventricular block [<1%]), bradycardia (IR: 2% to 10%; ER: <1%) (table 2), dependent edema (4%), edema (5% to 6%), exacerbation of angina pectoris (1% to 3%), hypertension (1% to 3%), lower extremity edema (1% to 3%), palpitations (1% to 3%), peripheral edema (IR: 1% to 7%; ER: 2%), peripheral ischemia (≤1%), peripheral vascular disease (1% to 3%), syncope (IR: ≤8%; ER: <1%), tachycardia (≤1%)
|
Drug (Carvedilol) |
Placebo |
Dosage Form |
Indication |
Number of Patients (Carvedilol) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
0.5% |
N/A |
Extended-release capsules |
Heart failure or myocardial infarction/left ventricular dysfunction |
N/A |
N/A |
|
2% |
0% |
Immediate-release tablets |
Hypertension |
1,142 |
462 |
|
9% |
1% |
Immediate-release tablets |
Mild to moderate heart failure |
765 |
437 |
|
7% |
N/A |
Immediate-release tablets |
Myocardial infarction and left ventricular dysfunction |
N/A |
N/A |
|
10% |
3% |
Immediate-release tablets |
Severe heart failure |
1,156 |
1,133 |
Dermatologic: Diaphoresis (≤1%), erythematous rash (≤1%), maculopapular rash (≤1%), pruritus (≤1%), psoriasiform eruption (≤1%), skin photosensitivity (≤1%)
Endocrine & metabolic: Albuminuria (1% to 3%), decreased libido (≤1%), diabetes mellitus (1% to 3%), hypercholesterolemia (4%), hyperkalemia (1% to 3%), hypertriglyceridemia (≤1%), hyperuricemia (1% to 3%), hypervolemia (1% to 3%), hypoglycemia (1% to 3%), hypokalemia (≤1%), hyponatremia (1% to 3%), hypovolemia (1% to 3%), increased nonprotein nitrogen (6%), weight loss (1% to 3%)
Gastrointestinal: Gastrointestinal pain (1% to 3%), melena (1% to 3%), nausea (IR: 4% to 9%; ER: 2%), periodontitis (1% to 3%), vomiting (6%), xerostomia (≤1%)
Genitourinary: Erectile dysfunction (1% to 3%), glycosuria (1% to 3%), hematuria (1% to 3%), urinary frequency (≤1%)
Hematologic & oncologic: Hypoprothrombinemia (1% to 3%), leukopenia (≤1%), purpuric disease (1% to 3%), thrombocytopenia (1% to 3%)
Hepatic: Increased gamma-glutamyl transferase (1% to 3%), increased serum alanine aminotransferase (1% to 3%), increased serum alkaline phosphatase (1% to 3%), increased serum aspartate aminotransferase (1% to 3%), increased serum bilirubin (≤1%)
Hypersensitivity: Hypersensitivity reaction (1% to 3%)
Nervous system: Cerebrovascular accident (1% to 3%), changes in thinking (≤1%), depression (1% to 3%), drowsiness (1% to 3%), emotional lability (≤1%), exacerbation of depression (≤1%), headache (5% to 8%), hypoesthesia (1% to 3%), hypotonia (1% to 3%), insomnia (IR: 2%; ER: 1%) (table 3), lack of concentration (≤1%), malaise (1% to 3%), nervousness (≤1%), nightmares (≤1%), paranoid ideation (≤1%), paresthesia (IR: 1% to 3%; ER: 1%), sleep disturbance (≤1%), vertigo (1% to 3%)
|
Drug (Carvedilol) |
Placebo |
Dosage Form |
Indication |
Number of Patients (Carvedilol) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% |
1% |
Immediate-release tablets |
Hypertension |
1,142 |
462 |
|
1% |
0% |
Extended-release capsules |
Hypertension |
253 |
84 |
Neuromuscular & skeletal: Arthralgia (6%), arthritis (1% to 3%), gout (1% to 3%), hypokinesia (≤1%), muscle cramps (1% to 3%)
Ophthalmic: Blurred vision (1% to 3%), visual disturbance (5%)
Otic: Tinnitus (≤1%)
Renal: Increased blood urea nitrogen (≤6%), increased serum creatinine (1% to 3%), kidney impairment (1% to 3%)
Respiratory: Asthma (≤1%), dyspnea (>3%), flu-like symptoms (1% to 3%), increased cough (5%), nasal congestion (ER: 1%), nasopharyngitis (ER: 4%), paranasal sinus congestion (ER: 1%), rales (4%)
Miscellaneous: Fever (1% to 3%)
<1%:
Cardiovascular: Bundle branch block, ischemic heart disease
Dermatologic: Alopecia, exfoliative dermatitis
Endocrine & metabolic: Decreased HDL cholesterol, respiratory alkalosis
Gastrointestinal: Gastrointestinal hemorrhage
Hematologic & oncologic: Abnormal lymphocytes, pancytopenia
Hypersensitivity: Nonimmune anaphylaxis
Nervous system: Amnesia, cerebrovascular disease, migraine, neuralgia, paresis, seizure
Otic: Auditory impairment
Respiratory: Bronchospasm
Frequency not defined (any formulation):
Hematologic & oncologic: Anemia
Respiratory: Pulmonary edema
Postmarketing (any formulation):
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome (Kowalski 1997), toxic epidermal necrolysis (Vlahovic-Palcevski 2010)
Genitourinary: Urinary incontinence
Hematologic & oncologic: Aplastic anemia
Hepatic: Hepatotoxicity (including toxic hepatitis) (Hagmeyer 2001; Rua 2019)
Hypersensitivity: Anaphylaxis, angioedema
Respiratory: Interstitial pneumonitis
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, or severe bradycardia (except in patients with a functioning artificial pacemaker); cardiogenic shock; severe hepatic impairment
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.
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 vasospastic 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 with reduced ejection fraction: Stabilize patients on heart failure regimen prior to initiation or titration of beta-blocker. Beta-blocker therapy should be initiated at very low doses with gradual and careful titration. Worsening heart failure or fluid retention may occur during upward titration; dose reduction and/or slower titration may be necessary. Adjustment of other medications (ACE inhibitors and/or diuretics) may also be required.
• 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.
Special populations:
• Older adult: 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 kidney 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.
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
Yes
Capsule ER 24 Hour Therapy Pack (Carvedilol Phosphate ER Oral)
10 mg (per each): $9.91 - $20.44
20 mg (per each): $9.91 - $20.44
40 mg (per each): $9.91 - $20.44
80 mg (per each): $9.91 - $20.44
Capsule ER 24 Hour Therapy Pack (Coreg CR Oral)
10 mg (per each): $37.14
20 mg (per each): $37.14
40 mg (per each): $37.14
80 mg (per each): $37.14
Tablets (Carvedilol Oral)
3.125 mg (per each): $0.21 - $2.14
6.25 mg (per each): $0.06 - $2.14
12.5 mg (per each): $0.07 - $2.14
25 mg (per each): $0.09 - $2.14
Tablets (Coreg Oral)
3.125 mg (per each): $11.81
6.25 mg (per each): $11.81
12.5 mg (per each): $11.81
25 mg (per each): $11.81
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.
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
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.
Oral: Immediate-release tablets: Administer with food.
Heart failure with reduced ejection fraction: Treatment of mild to severe chronic heart failure of ischemic or cardiomyopathic origin or left ventricular dysfunction following myocardial infarction (clinically stable with left ventricular ejection fraction ≤40%).
Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2018]).
Angina, chronic stable; Atrial fibrillation/flutter, maintenance of ventricular rate control; Myocardial infarction, early treatment and secondary prevention; Nonsustained ventricular tachycardia or ventricular premature beats, symptomatic; Variceal hemorrhage prophylaxis, primary
Carvedilol may be confused with atenolol, captopril, carbidopa, carteolol
Coreg may be confused with Corgard, Cortef, Cozaar
Substrate of CYP1A2 (minor), CYP2C9 (major), CYP2D6 (major), CYP2E1 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein/ABCB1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. 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
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. 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. Risk D: Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
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
Antidiabetic Agents: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic 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
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing 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: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Cannabis: Beta-Blockers may enhance the adverse/toxic effect of Cannabis. Specifically, the risk of hypoglycemia may be increased. 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. 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. 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: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
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 increase the serum concentration of Carvedilol. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Carvedilol. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. 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
DOBUTamine: Beta-Blockers may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Increase monitoring for clinical response and adverse effects. 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. Risk C: Monitor therapy
EPHEDrine (Systemic): Beta-Blockers may diminish the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy
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 (Vasoconstrictive CYP3A4 Substrates): Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Etilefrine: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may diminish the therapeutic effect of Etilefrine. Risk C: Monitor therapy
Etofylline: Beta-Blockers may diminish the therapeutic effect of Etofylline. Risk X: Avoid combination
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
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. Management: Consider alternatives to either grass pollen allergen extract (5 grass extract) or beta-blockers in patients with indications for both agents. Canadian product labeling specifically lists this combination as contraindicated. Risk D: Consider therapy modification
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: 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
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Insulins: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy
Isoproterenol: Beta-Blockers may diminish the therapeutic effect of Isoproterenol. 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
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Mavacamten: Beta-Blockers may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk C: Monitor therapy
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
Mivacurium: Beta-Blockers may enhance the therapeutic effect of Mivacurium. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. 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
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
Nitrendipine: May enhance the therapeutic 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
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic 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
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Patiromer: May decrease the serum concentration of Carvedilol. Management: Administer carvedilol at least 3 hours before or 3 hours after patiromer. Risk D: Consider therapy modification
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
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
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Reserpine: May enhance the bradycardic effect of Beta-Blockers. Reserpine may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
RifAMPin: May decrease the serum concentration of Carvedilol. Risk C: Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Succinylcholine: Beta-Blockers may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Sulfonylureas. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Sulfonylureas. Risk C: Monitor therapy
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: Carvedilol may increase the serum concentration of Talazoparib. Management: In breast cancer, if concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. In prostate cancer, monitor patients for increased adverse events. Risk D: Consider therapy modification
Tasimelteon: Beta-Blockers may diminish the therapeutic effect of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider therapy modification
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy
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
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification
Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
White Birch Allergen Extract: Beta-Blockers may enhance the adverse/toxic effect of White Birch Allergen Extract. Specifically, beta-blockers may reduce the effectiveness of beta-agonists that may be required to treat systemic reactions to white birch allergen extract. Risk X: Avoid combination
Food decreases rate but not extent of absorption. Management: Administration with food minimizes risks of orthostatic hypotension.
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Carvedilol is not considered a preferred agent for use in pregnant patients; consider transitioning to a preferred agent in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
Impotence is noted in product labeling following use of carvedilol. As a class, outcomes from available studies evaluating beta-blockers and sexual dysfunction are inconsistent, and the negative effects on erectile function are considered controversial. A clear relationship between use of beta-blockers and erectile dysfunction has not been established. Hypertension itself is associated with erectile dysfunction. Patients on a beta-blocker presenting with sexual dysfunction should be evaluated for underlying disease (Farmakis 2022; Levine 2012; Semet 2017; Terentes-Printzios 2022; Viigimaa 2020).
Exposure to beta-blockers during pregnancy may increase the risk for adverse events in the neonate. If maternal use of a beta-blocker is needed, monitor fetal growth during pregnancy; monitor the newborn for 48 hours after delivery for bradycardia, hypoglycemia, and respiratory depression (ESC [Regitz-Zagrosek 2018]).
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment of hypertension is initiated during pregnancy, agents other than carvedilol may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]). Carvedilol may be considered for use in pregnant patients with heart failure (ESC [Regitz-Zagrosek 2018]).
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 consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Use of a beta-blocker other than carvedilol may be preferred in lactating patients (ESC [Cífková 2020]).
Should be taken with food to minimize the risk of orthostatic hypotension.
ECG, heart rate, blood pressure; kidney function; liver function; blood glucose in patients with diabetes; signs and symptoms of bronchospasm in patients with existing bronchospastic disease; mental alertness.
Blood pressure goal: May vary depending on clinical conditions, different clinical practice guidelines, and expert opinion. Refer to "Clinical Practice Guidelines" for specific treatment goals.
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).
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 (Läer 2002)
Children and Adolescents 5.5 to 19 years (n=7): 3.6 hours (Läer 2002)
Adults 7 to 10 hours; some have reported lower values: Adults 24 to 37 years (n=9): 5.2 hours (Läer 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)
Altered kidney function: Plasma concentrations may be higher (40% to 50% in moderate to severe kidney impairment).
Hepatic function impairment: Severe hepatic impairment (cirrhosis) patients have a 4- to 7-fold increase in concentrations.
Older adult: Plasma levels are about 50% higher.
Heart failure: AUC and Cmax increased up to 100%.
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