Carvedilol

Carvedilol is a third-generation beta blocker: it blocks not only beta-1 and beta-2 receptors but also alpha-1 receptors. This triple blockade leads to a reduction in blood pressure and takes strain off the heart.

Carvedilol has been studied particularly well in chronic heart failure and has reduced mortality in heart failure in large studies (COPERNICUS, COMET). It is used for high blood pressure, chronic heart failure, and coronary heart disease.

For high blood pressure, carvedilol is usually taken once daily, and for angina pectoris and heart failure twice daily. Available products include Carvedilol-ratiopharm® and Dilatrend®.

Carvedilol has a triple mechanism of action:

Beta-1 blockade (in the heart):

• Lowers heart rate and force of contraction
• Reduces oxygen consumption
• Inhibits renin release

Beta-2 blockade (in the lungs and blood vessels):

• Not cardioselective
• Caution: bronchospasm possible in asthma

Alpha-1 blockade (in the blood vessels):

• Dilates the peripheral blood vessels
• Lowers vascular resistance
• Reduces the afterload of the heart
• Improves blood flow

Additional properties:

• Antioxidant effect
• Stabilization of cell membranes
• No negative effect on insulin sensitivity
• Favorable effects on lipid metabolism

Onset of action: Maximum blood pressure reduction after 1-2 hours. Stable control after 1-2 weeks.

Carvedilol is suitable for:

• Adults with high blood pressure
• Chronic stable heart failure (NYHA II-IV)
• Chronic stable angina pectoris

Especially recommended for:

• Heart failure (strong evidence from studies)
• High blood pressure with increased peripheral resistance
• Patients after a heart attack

Not suitable for:

• Bronchial asthma (not cardioselective!)
• Grade II/III AV block
• Severe bradycardia
• Decompensated heart failure
• Severe liver failure
• Cardiogenic shock

High blood pressure:

• Starting dose: 12.5 mg once daily (days 1 and 2)
• Then: 25 mg once or twice daily
• Maximum dose: 50 mg daily (divided)

Heart failure:

• Starting dose: 3.125 mg twice daily
• Increase every 2 weeks: 6.25 mg → 12.5 mg → 25 mg (2x each)
• Target dose: 25 mg twice daily (up to 85 kg) or 50 mg twice daily (over 85 kg)

Angina pectoris:

• Starting dose: 12.5 mg twice daily
• After 2 days: 25 mg twice daily

Available strengths:

• 3.125 mg, 6.25 mg, 12.5 mg, 25 mg tablets

How to take:

• For high blood pressure: usually once daily
• For angina pectoris and heart failure: twice daily
• Take with meals (better tolerability, slower absorption)
• With sufficient water
• Patients with heart failure: stand up slowly (orthostatic hypotension)

In heart failure:

• Very slow dose increase (every 2 weeks)
• Start only when heart failure is stable
• Close medical monitoring
• If the condition worsens: reduce the dose

Important notes:

• Do not stop abruptly
• Regular blood pressure, pulse, and weight checks
• People with asthma: carvedilol is not suitable (not cardioselective)

Carvedilol must not be taken in case of:

• Hypersensitivity to carvedilol
• Decompensated heart failure (IV therapy required)
• Severe liver failure
• Grade II/III AV block (without a pacemaker)
• Severe bradycardia (below 50/min)
• Sick sinus syndrome
• Cardiogenic shock
• Severe hypotension (below 85 mmHg systolic)
• Bronchial asthma or severe COPD
• Untreated pheochromocytoma

Caution in case of:

• Diabetes mellitus (can mask symptoms of hypoglycemia)
• Peripheral circulatory disorders
• Prinzmetal angina
• Contact lens wearers (reduced tear fluid)
• Psoriasis

Pregnancy: Carvedilol should not be used during pregnancy unless the expected benefit outweighs the possible risks. Beta blockers can lead to growth retardation and bradycardia in the newborn.

Very common (over 10%):

• Dizziness
• Headache
• Fatigue (especially at the beginning)

Common (1-10%):

• Bradycardia
• Orthostatic hypotension (especially in heart failure)
• Edema
• Weight gain
• Gastrointestinal complaints
• Visual disturbances
• Reduced tear fluid

Uncommon (0.1-1%):

• Depressed mood
• Sleep disorders
• Erectile dysfunction
• Skin rash
• Shortness of breath, bronchospasm
• Constipation

Rare:

• Severe allergic reactions
• Worsening of kidney function
• Thrombocytopenia
• Worsening of psoriasis

Note: Orthostatic dizziness occurs especially at the start of therapy and when the dose is increased. Standing up slowly is recommended.

Contraindicated with:

• Verapamil or diltiazem IV
• MAO inhibitors (except MAO-B inhibitors)

Caution with:

• Digoxin → increased digoxin levels
• Insulin and antidiabetic drugs → masking and intensification of hypoglycemia
• Rifampicin → decreased carvedilol levels
• Cyclosporine → increased cyclosporine levels
• Clonidine → rebound effect if both are stopped at the same time
• Anesthetics → increased hypotension and bradycardia
• CYP2D6 inhibitors (fluoxetine, paroxetine) → increased carvedilol levels

Important: Carvedilol is metabolized via CYP2D6 and CYP2C9. Inhibitors of these enzymes can increase the effect of carvedilol.