Carvedilol
Non-selective beta blocker with alpha-1 blocking activity for high blood pressure, angina pectoris, and chronic heart failure
Carvedilol is a prescription medication belonging to the beta blocker class. Unlike most beta blockers, carvedilol blocks both beta-adrenergic and alpha-1 adrenergic receptors, providing vasodilating properties in addition to heart rate and blood pressure reduction. It is primarily used to treat high blood pressure, chronic stable angina pectoris, and moderate to severe chronic heart failure. This comprehensive guide covers dosage, side effects, drug interactions, and important safety information based on international clinical guidelines.
📊 Quick Facts About Carvedilol
💡 Key Takeaways About Carvedilol
- Dual mechanism of action: Carvedilol blocks both beta and alpha-1 receptors, providing vasodilation in addition to heart rate reduction — unique among commonly used beta blockers
- Proven mortality benefit in heart failure: Landmark trials (COPERNICUS, COMET) demonstrated significant reductions in death and hospitalization in patients with chronic heart failure
- Slow dose titration required: Treatment must be started at a very low dose and increased gradually over weeks, especially in heart failure patients
- Never stop abruptly: Sudden discontinuation can cause rebound hypertension, worsening angina, or heart attack — always taper over 1–2 weeks
- Avoid grapefruit: Grapefruit juice can significantly increase carvedilol blood levels, leading to unpredictable side effects
What Is Carvedilol and What Is It Used For?
Quick answer: Carvedilol is a non-selective beta blocker with additional alpha-1 blocking activity. It is used to treat high blood pressure (hypertension), chronic stable angina pectoris (chest pain), and moderate to severe chronic heart failure as an add-on to standard therapy.
Carvedilol belongs to a unique subclass of beta blockers known as combined alpha-beta blockers. While traditional beta blockers primarily block beta-1 adrenergic receptors in the heart to reduce heart rate and contractility, carvedilol also blocks beta-2 receptors and alpha-1 receptors in blood vessels. This triple-receptor blockade results in vasodilation (widening of blood vessels), which helps to lower blood pressure more effectively and with less peripheral vasoconstriction compared to selective beta blockers.
The medication is classified under ATC code C07AG02, placing it in the group of alpha and beta blocking agents. Carvedilol has been extensively studied in large-scale clinical trials and is recognized by the World Health Organization (WHO) as an important cardiovascular medication. The European Society of Cardiology (ESC) and the American Heart Association (AHA) both recommend carvedilol as one of the evidence-based beta blockers for the treatment of heart failure with reduced ejection fraction (HFrEF).
Approved Indications
Carvedilol is approved for the following conditions:
- High blood pressure (hypertension): Carvedilol effectively reduces both systolic and diastolic blood pressure through its combined beta and alpha-blocking actions. It can be used alone or in combination with other antihypertensive medications, particularly thiazide diuretics. The vasodilating properties of carvedilol make it particularly useful in patients who experience cold extremities with selective beta blockers.
- Chronic stable angina pectoris: By reducing heart rate and myocardial oxygen demand, carvedilol alleviates the chest pain associated with insufficient blood flow to the heart muscle. It is effective for managing exercise-induced angina and reducing the frequency and severity of anginal episodes.
- Chronic heart failure: Carvedilol is indicated for the treatment of moderate to severe stable chronic heart failure as an adjunct to standard therapy, which typically includes ACE inhibitors (or ARBs), diuretics, and optionally digitalis. Treatment with carvedilol should only be initiated when the patient's condition has been stable on standard heart failure therapy for at least four weeks.
Mechanism of Action
Carvedilol exerts its therapeutic effects through multiple mechanisms. By blocking beta-1 receptors in the heart, it reduces heart rate, cardiac contractility, and cardiac output, thereby decreasing the workload on the heart. The blockade of beta-2 receptors, while generally undesirable in the lungs (hence its contraindication in asthma), contributes to overall sympathetic nervous system suppression. The alpha-1 receptor blockade in blood vessels causes peripheral vasodilation, which reduces afterload (the resistance the heart must pump against) and helps maintain peripheral blood flow.
In heart failure, carvedilol counteracts the harmful effects of chronic neurohormonal activation — the body's excessive sympathetic (fight-or-flight) response that ultimately damages the failing heart. Additionally, carvedilol possesses antioxidant properties that may contribute to its cardioprotective effects by reducing oxidative stress on cardiac cells. These combined actions explain why carvedilol has demonstrated greater mortality reduction in heart failure compared to some selective beta blockers in head-to-head clinical trials.
What Should You Know Before Taking Carvedilol?
Quick answer: Carvedilol must not be used if you have asthma, severe heart failure requiring IV treatment, liver problems, severe bradycardia, certain heart block conditions, very low blood pressure, or if you take MAO inhibitors or IV verapamil/diltiazem. Discuss all medical conditions and medications with your doctor before starting treatment.
Contraindications
Carvedilol must not be taken in the following situations:
- Allergy to carvedilol or any of the inactive ingredients in the formulation
- Bronchial asthma or severe bronchospasm: The non-selective beta-blocking action can cause dangerous bronchoconstriction in patients with asthma or severe chronic obstructive pulmonary disease (COPD)
- Decompensated heart failure requiring intravenous inotropic therapy — carvedilol is only for stable chronic heart failure
- Severe hepatic (liver) impairment: Carvedilol is extensively metabolized by the liver and can accumulate to dangerous levels
- Second- or third-degree AV block (unless a permanent pacemaker is in place)
- Severe bradycardia (resting heart rate below 50 beats per minute)
- Sick sinus syndrome (including sinoatrial block)
- Cardiogenic shock: A condition where the heart cannot pump enough blood to meet the body's needs
- Severe hypotension (systolic blood pressure below 85 mmHg)
- Acute pulmonary embolism causing chest pain and shortness of breath
- Prinzmetal's (variant) angina: A rare form of chest pain caused by coronary artery spasm
- Untreated pheochromocytoma: A rare tumor of the adrenal gland that produces excess adrenaline
- Metabolic acidosis: An abnormally low blood pH
- Concurrent use of MAO inhibitors (except MAO-B inhibitors)
- Intravenous verapamil or diltiazem: The combination can cause severe bradycardia, AV block, and cardiac arrest
- Breastfeeding: Carvedilol may pass into breast milk
Warnings and Precautions
Talk to your doctor before taking carvedilol if any of the following apply to you:
- Lung conditions: Even mild COPD or chronic bronchitis may be worsened by carvedilol's non-selective beta blockade. Your doctor may need to monitor lung function carefully.
- Kidney problems: Kidney function should be monitored during treatment, particularly in heart failure patients, as carvedilol may cause transient worsening of renal function.
- Diabetes mellitus: Carvedilol can mask the typical warning signs of low blood sugar (hypoglycemia), particularly rapid heartbeat and tremor. Blood glucose monitoring should be more frequent, especially when starting treatment or adjusting the dose.
- Contact lens wearers: Carvedilol may reduce tear production, causing dry eyes and discomfort.
- Peripheral vascular disease: The reduction in cardiac output and potential vasoconstriction may worsen symptoms of intermittent claudication or Raynaud's phenomenon (cold fingers and toes).
- Thyroid disorders: Beta blockers can mask the cardiovascular signs of hyperthyroidism (overactive thyroid). Abrupt withdrawal may precipitate a thyroid storm.
- History of severe allergic reactions (anaphylaxis): Patients taking beta blockers may be more resistant to the effects of epinephrine (adrenaline) used to treat anaphylactic reactions. Higher doses of epinephrine may be needed. Always inform healthcare providers that you take carvedilol.
- Psoriasis: Beta blockers, including carvedilol, have been reported to trigger or worsen psoriasis in some patients.
- History of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): These life-threatening skin reactions have been rarely reported with carvedilol. Seek immediate medical attention if you develop widespread skin blistering, mouth ulcers, or eye inflammation.
Treatment with carvedilol must never be stopped suddenly. This is especially critical for patients with coronary artery disease, as abrupt withdrawal can trigger rebound angina, heart attack, or life-threatening arrhythmias due to an abrupt increase in heart rate and blood pressure. The dose should be gradually reduced over a period of at least two weeks under medical supervision.
Elderly Patients
Older patients may be more sensitive to the blood pressure-lowering and heart rate-reducing effects of carvedilol. Dizziness and postural hypotension (a drop in blood pressure when standing up) are more common in elderly patients. Close monitoring is required, and doses should be increased more cautiously. Starting with the lowest available dose and titrating slowly is especially important in this population.
Children and Adolescents
Carvedilol is not recommended for children and adolescents under 18 years of age due to insufficient data on its safety and efficacy in this age group.
Pregnancy and Breastfeeding
Carvedilol should generally not be used during pregnancy unless the potential benefit to the mother clearly outweighs the risk to the fetus. Beta blockers can reduce blood flow to the placenta, potentially causing fetal growth restriction, bradycardia (low heart rate), and hypoglycemia (low blood sugar) in the newborn. If you become pregnant while taking carvedilol, do not stop the medication abruptly — contact your doctor for guidance on safe alternatives.
Carvedilol must not be used during breastfeeding. Studies in animals have shown that carvedilol and its metabolites are excreted in breast milk. The potential effects on the nursing infant are not fully known, and therefore breastfeeding is contraindicated.
Driving and Operating Machinery
Carvedilol may cause dizziness, fatigue, and blurred vision, particularly at the start of treatment or when doses are changed. If you experience these symptoms, do not drive, operate machinery, or perform activities that require alertness. Alcohol can enhance these effects and should be consumed in moderation or avoided. Individual reactions vary — consult your doctor if you are concerned about your ability to drive safely.
How Does Carvedilol Interact with Other Drugs?
Quick answer: Carvedilol has significant interactions with calcium channel blockers (verapamil, diltiazem), antiarrhythmic drugs, diabetes medications, clonidine, MAO inhibitors, and CYP2D6 inhibitors such as fluoxetine and paroxetine. Grapefruit juice must also be avoided. Always inform your doctor of all medications you are taking.
Carvedilol is extensively metabolized by the liver via cytochrome P450 enzymes, particularly CYP2D6 and CYP2C9. Drugs that inhibit or induce these enzymes can significantly alter carvedilol blood levels. Additionally, carvedilol's pharmacological effects can be additive or synergistic with other cardiovascular medications. The following sections detail the most clinically important drug interactions.
Major Interactions
| Drug / Class | Interaction Effect | Clinical Action |
|---|---|---|
| Verapamil / Diltiazem (IV) | Severe bradycardia, AV block, hypotension, cardiac arrest | Contraindicated — never give IV verapamil or diltiazem to patients on carvedilol |
| MAO Inhibitors | Exaggerated hypotension and bradycardia; unpredictable cardiovascular effects | Contraindicated (except MAO-B inhibitors); do not combine |
| Clonidine | Risk of rebound hypertensive crisis if clonidine is stopped first | Always stop carvedilol first, then taper clonidine over several days |
| Digoxin | Increased digoxin levels; additive AV conduction slowing and bradycardia | Monitor digoxin levels and heart rate closely; dose adjustment may be needed |
| Amiodarone | Additive bradycardia and AV conduction block; increased risk of cardiac arrest | Monitor ECG and heart rate closely; consider dose reduction |
| Insulin / Oral Antidiabetics | Masking of hypoglycemic symptoms (tachycardia); enhanced blood sugar-lowering effect | Increase blood glucose monitoring; adjust diabetes medication as needed |
| Epinephrine (Adrenaline) | Reduced effectiveness of epinephrine in anaphylaxis due to beta-blockade | Higher epinephrine doses may be needed; inform emergency providers you take carvedilol |
Moderate Interactions
| Drug / Class | Interaction Effect | Clinical Action |
|---|---|---|
| Fluoxetine / Paroxetine | CYP2D6 inhibition increases carvedilol levels; excessive beta-blockade | Monitor heart rate and blood pressure; dose reduction of carvedilol may be needed |
| Rifampicin | CYP enzyme induction reduces carvedilol levels by up to 70% | Carvedilol may become ineffective; dose increase or alternative therapy needed |
| Cimetidine | Increases carvedilol blood levels by inhibiting hepatic metabolism | Monitor for excessive blood pressure lowering; consider alternative acid suppressant |
| Cyclosporine / Tacrolimus | Increased levels of cyclosporine/tacrolimus; increased nephrotoxicity risk | Monitor trough levels of immunosuppressant; adjust dose as needed |
| NSAIDs (Ibuprofen, Naproxen) | Reduced blood pressure-lowering effect of carvedilol; fluid retention | Monitor blood pressure; use lowest effective NSAID dose for shortest duration |
| Dihydropyridine Calcium Blockers | Additive hypotension and potential negative cardiac effects | Monitor blood pressure and heart rate; use with caution |
| Reserpine / Guanethidine | Excessive sympathetic blockade; profound bradycardia and hypotension | Monitor cardiovascular parameters closely; avoid combination if possible |
| Inhaled Beta-2 Agonists (Salbutamol) | Carvedilol blocks beta-2 receptors, reducing effectiveness of bronchodilators | Use with extreme caution in patients with respiratory conditions; monitor lung function |
Carvedilol must not be taken with grapefruit or grapefruit juice. Grapefruit inhibits CYP enzymes in the intestinal wall, which can significantly increase blood levels of carvedilol and lead to unpredictable and potentially dangerous side effects, including excessive blood pressure lowering and severe bradycardia. Avoid all grapefruit products while taking this medication.
If you are scheduled for surgery, inform your anesthesiologist that you take carvedilol. Certain anesthetic agents (such as ether, cyclopropane, and trichloroethylene) can depress cardiac function and, when combined with carvedilol's beta-blocking effects, may cause dangerously low blood pressure. Your medical team will take appropriate precautions to manage your blood pressure and heart rate during the procedure.
What Is the Correct Dosage of Carvedilol?
Quick answer: Carvedilol dosing varies by indication. For hypertension, the starting dose is typically 12.5 mg once daily, increasing to 25 mg once daily. For angina, 12.5 mg twice daily increasing to 25 mg twice daily. For heart failure, treatment starts very low at 3.125 mg twice daily and is slowly titrated upward over several weeks to a target of 25 mg twice daily (or 50 mg twice daily for patients over 85 kg).
Carvedilol dosing requires careful individualization based on the patient's condition, response to treatment, and tolerability. The tablets should be taken with food and a glass of water to reduce the rate of absorption and minimize the risk of postural hypotension (dizziness upon standing). The following dosing guidelines are based on international clinical practice.
Adults
| Indication | Starting Dose | Usual Maintenance Dose | Maximum Dose |
|---|---|---|---|
| Hypertension | 12.5 mg once daily for 2 days | 25 mg once daily | 50 mg/day (25 mg twice daily) |
| Angina Pectoris | 12.5 mg twice daily for 2 days | 25 mg twice daily | 100 mg/day (50 mg twice daily) |
| Heart Failure | 3.125 mg twice daily | Titrate every 2+ weeks: 6.25 → 12.5 → 25 mg twice daily | 25 mg twice daily (50 mg BD if >85 kg) |
Heart Failure Titration Schedule
In heart failure, carvedilol must be titrated very gradually. Treatment should only be initiated when the patient has been stable on standard heart failure therapy (ACE inhibitors, diuretics, with or without digitalis) for at least four weeks, with no change in dose of existing medications. Your doctor will monitor you closely during the titration period, particularly watching for signs of worsening heart failure, fluid retention, low blood pressure, or excessively slow heart rate.
Heart Failure Dose Titration
- Week 1–2: 3.125 mg twice daily
- Week 3–4: 6.25 mg twice daily (if tolerated)
- Week 5–6: 12.5 mg twice daily (if tolerated)
- Week 7+: 25 mg twice daily (target dose)
- Patients >85 kg: May increase to 50 mg twice daily if tolerated and no severe heart failure
Elderly Patients
Elderly patients are more susceptible to the hypotensive and bradycardic effects of carvedilol. For hypertension, the recommended starting dose is 12.5 mg once daily, which may be sufficient for adequate blood pressure control. The dose may be cautiously increased if needed. For angina, the maximum recommended dose in elderly patients is 25 mg twice daily (50 mg/day), rather than the standard maximum of 100 mg/day in younger adults.
Hepatic Impairment
Patients with mild to moderate liver impairment may require lower doses, as determined by their doctor. Carvedilol is contraindicated in patients with severe hepatic impairment due to the risk of drug accumulation and toxicity.
Renal Impairment
Dose adjustments are generally not required for patients with kidney impairment, but the dose should be individualized by the treating physician. Close monitoring of kidney function is recommended during treatment, particularly in heart failure patients.
Missed Dose
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a missed one.
Overdose
If you or someone else has taken too much carvedilol, seek emergency medical care immediately. Symptoms of overdose may include: severely slow heart rate (bradycardia), dizziness or fainting, difficulty breathing, wheezing, sinus arrest (temporary cessation of heart rhythm), extreme fatigue, and loss of consciousness. Bring the medication packaging with you to the hospital.
What Are the Side Effects of Carvedilol?
Quick answer: Very common side effects (more than 1 in 10 users) include dizziness, headache, fatigue, weakness, worsening heart failure symptoms, and low blood pressure. Common side effects include slow heart rate, weight gain, high cholesterol, depression, visual disturbances, fluid retention, cold extremities, nausea, vomiting, and diarrhea. Most side effects are mild and tend to improve during the first weeks of treatment.
Like all medications, carvedilol can cause side effects, although not everyone experiences them. Many side effects are dose-related and more common at the start of treatment or when the dose is increased. Dizziness, headache, fatigue, and low blood pressure are typically the earliest side effects and usually improve as your body adjusts to the medication. Your doctor will start with a low dose and increase gradually to minimize these effects.
- Signs of severe allergic reaction: sudden swelling of the throat, face, lips, or mouth causing difficulty breathing or swallowing
- Chest pain with simultaneous shortness of breath, sweating, and nausea (possible heart attack)
- Decreased urination and leg swelling (signs of kidney problems)
- Severe skin reactions: widespread rash, redness, blistering on lips, around eyes, or in the mouth, peeling skin (signs of Stevens-Johnson syndrome or toxic epidermal necrolysis)
- Very low blood sugar (hypoglycemia) that may lead to seizures or loss of consciousness
Very Common
Affects more than 1 in 10 people
- Dizziness
- Headache
- Fatigue and weakness
- Heart failure symptoms (chest pain, tiredness, shortness of breath, swollen limbs)
- Low blood pressure (hypotension) — causing dizziness or lightheadedness
Common
Affects up to 1 in 10 people
- Respiratory tract infections (bronchitis, pneumonia, upper respiratory infections)
- Urinary tract infections
- Anemia (low red blood cell count)
- Weight gain
- Elevated cholesterol levels
- Worsened blood sugar control in diabetic patients
- Depression
- Fainting (syncope)
- Visual disturbances, burning or dry eyes due to reduced tear production
- Slow heart rate (bradycardia)
- Dizziness or lightheadedness when standing up (orthostatic hypotension)
- Fluid retention and swelling (edema) — hands, feet, ankles, legs
- Poor peripheral circulation — cold hands and feet, pallor, tingling, leg pain when walking
- Breathing difficulties
- Nausea and vomiting
- Diarrhea
- Stomach pain and indigestion
- Pain in extremities
- Kidney problems, including changes in urination frequency
Uncommon
Affects up to 1 in 100 people
- Sleep disturbances and insomnia
- Nightmares
- Hallucinations and confusion
- Tingling or numbness in hands or feet (paresthesia)
- Skin rash, hives (urticaria), itching, and dry skin
- Erectile dysfunction (impotence)
- Constipation
- Disturbances in heart conduction (AV block)
- Chest pain from narrowed coronary arteries (worsened angina)
Rare
Affects up to 1 in 1,000 people
- Low platelet count (thrombocytopenia) — easy bruising and nosebleeds
- Nasal congestion, wheezing, and flu-like symptoms
- Dry mouth
Very Rare
Affects up to 1 in 10,000 people
- Low white blood cell count (leukopenia) — increased risk of infections in mouth, gums, throat, lungs
- Severe allergic reactions (anaphylaxis) — difficulty breathing or swallowing due to sudden swelling
- Liver function abnormalities (detected in blood tests)
- Urinary incontinence in some women (usually resolves when treatment stops)
- Psychotic episodes
Not Known
Frequency cannot be estimated from available data
- Hair loss (alopecia)
- Excessive sweating (hyperhidrosis)
- Unmasking of latent diabetes mellitus
- Sinus arrest in predisposed patients (elderly, those with existing bradycardia or sinus node dysfunction)
Most of the very common side effects — dizziness, headache, weakness, and fatigue — are typically mild and occur most frequently at the beginning of treatment. They tend to improve as your body adjusts to the medication. If side effects persist or become troublesome, speak with your doctor. Do not stop taking carvedilol without medical advice.
How Should You Store Carvedilol?
Quick answer: Store carvedilol tablets below 25°C (77°F) in the original packaging to protect from light. Keep out of reach of children. Do not use after the expiration date printed on the packaging.
Proper storage of carvedilol is essential to maintain the medication's effectiveness and safety. Follow these storage guidelines:
- Temperature: Store at or below 25°C (77°F). Do not freeze.
- Light protection: Keep the tablets in their original blister packaging to protect them from light, as carvedilol is light-sensitive.
- Moisture: Store in a dry place, away from bathrooms or humid environments.
- Child safety: Keep out of sight and reach of children at all times.
- Expiration: Do not use carvedilol after the expiration date (EXP) printed on the blister pack and outer carton. The expiration date refers to the last day of that month.
- Disposal: Do not dispose of medications via household waste or drain. Ask your pharmacist about proper disposal methods to help protect the environment.
What Does Carvedilol Contain?
Quick answer: The active ingredient is carvedilol, available in strengths of 3.125 mg, 6.25 mg, 12.5 mg, and 25 mg per tablet. Inactive ingredients include lactose monohydrate, microcrystalline cellulose, crospovidone, povidone K30, colloidal anhydrous silica, magnesium stearate, and red iron oxide (E 172).
Understanding the composition of your medication helps identify potential allergens and inactive ingredients that may affect tolerance.
Active Ingredient
Each tablet contains carvedilol as the active pharmaceutical ingredient. Carvedilol is chemically described as (±)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol. It is a racemic mixture with the S(-) enantiomer primarily responsible for beta-blockade and both enantiomers contributing to alpha-1 blockade.
Inactive Ingredients (Excipients)
- Lactose monohydrate — a filler/binder. Patients with lactose intolerance should consult their doctor before use.
- Microcrystalline cellulose — a filler and binder
- Crospovidone — a disintegrant that helps the tablet break apart for absorption
- Povidone K30 — a binder
- Colloidal anhydrous silica — a flow agent
- Magnesium stearate — a lubricant
- Red iron oxide (E 172) — a coloring agent
Tablet Appearance
Carvedilol 3.125 mg tablets are typically light pink, round, convex tablets with a score line, marked "C1" on one side. The score line allows the tablet to be divided into equal halves if needed. Available pack sizes include 14, 20, 28, 30, 50, 56, 60, 98, and 100 tablets in aluminum/PVC blisters. Not all pack sizes may be available in every country.
Frequently Asked Questions About Carvedilol
Carvedilol is used to treat three main conditions: high blood pressure (hypertension), chronic stable angina pectoris (chest pain caused by reduced blood flow to the heart), and moderate to severe chronic heart failure as an add-on to standard therapy. It belongs to the class of non-selective beta blockers with additional alpha-1 blocking activity, which means it both slows the heart rate and relaxes blood vessels. Carvedilol is one of only three beta blockers (alongside bisoprolol and metoprolol succinate) with proven mortality benefits in heart failure.
The most common side effects of carvedilol (affecting more than 1 in 10 users) are dizziness, headache, fatigue and weakness, worsening heart failure symptoms, and low blood pressure. Common side effects (up to 1 in 10 users) include slow heart rate, weight gain, elevated cholesterol, poor blood sugar control in diabetics, depression, visual disturbances, fluid retention, cold hands and feet, breathing problems, nausea, vomiting, and diarrhea. Most of these side effects are mild and tend to improve after the first few weeks as your body adjusts to the medication.
No, you should never stop taking carvedilol abruptly. Sudden discontinuation is particularly dangerous in patients with coronary artery disease, as it can trigger a rebound increase in heart rate and blood pressure, potentially leading to severe angina, heart attack, or life-threatening arrhythmias. The dose should always be gradually reduced over a period of at least 1–2 weeks under the supervision of your doctor. If you experience worsening symptoms during the tapering process, contact your healthcare provider immediately.
Carvedilol is unique because it blocks three types of receptors: beta-1 receptors in the heart, beta-2 receptors in the lungs and blood vessels, and alpha-1 receptors in blood vessels. Metoprolol and bisoprolol are beta-1 selective, meaning they primarily target the heart with less effect on the lungs. Carvedilol's alpha-1 blockade causes vasodilation, which can be beneficial for blood pressure but also means more first-dose hypotension. However, because carvedilol blocks beta-2 receptors, it is generally unsuitable for patients with asthma — unlike the more selective agents. The landmark COMET trial showed carvedilol reduced all-cause mortality by 17% compared to metoprolol tartrate in heart failure patients.
Carvedilol is generally not recommended during pregnancy unless the potential benefits to the mother clearly outweigh the potential risks to the fetus. Beta blockers can reduce blood flow to the placenta, which may cause intrauterine growth restriction, fetal bradycardia (slow heart rate), and neonatal hypoglycemia (low blood sugar). Carvedilol must not be used during breastfeeding. If you need blood pressure treatment during pregnancy, your doctor will likely consider alternatives with better-established safety profiles, such as labetalol or methyldopa. Never stop carvedilol abruptly if you discover you are pregnant — consult your doctor for guidance.
Grapefruit and grapefruit juice contain compounds called furanocoumarins that inhibit CYP3A4 enzymes in the intestinal wall. These enzymes are partly responsible for breaking down carvedilol before it enters the bloodstream. When these enzymes are inhibited, significantly more carvedilol is absorbed, leading to higher and less predictable blood levels. This can result in excessive blood pressure lowering, severe bradycardia, dizziness, and fainting. You should avoid all grapefruit products while taking carvedilol.
For heart failure, carvedilol is started at the very low dose of 3.125 mg twice daily. This is a critical safety measure because heart failure patients are particularly sensitive to the blood pressure-lowering and heart rate-reducing effects of beta blockers. Treatment should only be initiated when your condition has been stable on standard heart failure therapy (ACE inhibitors, diuretics) for at least four weeks. The dose is then doubled every two weeks — to 6.25 mg, then 12.5 mg, then 25 mg twice daily — but only if each increase is tolerated. For patients weighing over 85 kg without severe heart failure, the maximum dose is 50 mg twice daily.
References
This article is based on the following peer-reviewed sources and international medical guidelines:
- Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Circulation. 2002;106(17):2194-2199. doi:10.1161/01.CIR.0000035653.72855.BF
- Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET). Lancet. 2003;362(9377):7-13. doi:10.1016/S0140-6736(03)13800-7
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021;42(36):3599-3726. doi:10.1093/eurheartj/ehab368
- Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. Journal of Hypertension. 2023;41(12):1874-2071. doi:10.1097/HJH.0000000000003480
- World Health Organization. WHO Model List of Essential Medicines — 23rd List (2023). Geneva: WHO; 2023.
- National Institute for Health and Care Excellence (NICE). Chronic heart failure in adults: diagnosis and management (NG106). London: NICE; 2018 (updated 2023).
- European Medicines Agency. Summary of Product Characteristics: Carvedilol. Amsterdam: EMA; accessed 2026.
- U.S. Food and Drug Administration. Coreg (carvedilol) — FDA Label. Silver Spring, MD: FDA.
- Joint Formulary Committee. British National Formulary (BNF) — Carvedilol. London: BMJ Group and Pharmaceutical Press; 2025.
- Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. New England Journal of Medicine. 1996;334(21):1349-1355. doi:10.1056/NEJM199605233342101
About This Article
This article was written by the iMedic Medical Editorial Team, comprising licensed physicians specializing in clinical pharmacology, cardiology, and internal medicine. All content is reviewed according to international guidelines (WHO, EMA, FDA, ESC, NICE) and follows the GRADE evidence framework.
Reviewed by the iMedic Medical Review Board — an independent panel of specialist physicians who evaluate all content for medical accuracy, completeness, and adherence to current evidence-based guidelines.
Evidence Level 1A — Based on systematic reviews, meta-analyses, and randomized controlled trials (COPERNICUS, COMET, U.S. Carvedilol Heart Failure Study). All medical claims are referenced to peer-reviewed literature and international clinical guidelines.
Last medically reviewed: . This article is updated regularly to reflect the latest clinical evidence and guideline changes. If you notice any inaccuracies, please contact us.