Carvedilol

Carvedilol is a cardiovascular drug whose main pharmacological action is non-selective antagonism of β-adrenergic receptors but which also possesses appreciable α-adrenergic antagonistic activity. It also has antiproliferative properties and is a scavenger of reactive free oxidant radicals. It is used in the treatment of hypertension, angina pectoris, and congestive heart failure.

Carvedilol is indicated for the treatment of mild, moderate, or severe heart failure of ischemic or cardiomyopathic origin, in conjunction with digitalis, diuretics, and ACE inhibitors, to reduce disease progression. It may be used in patients unable to tolerate an ACE inhibitor.

• Hypertension
• Angina pectoris
• Heart failure (mild, moderate, severe - ischemic or cardiomyopathic origin)

Hypertension: Initial 12.5 mg once daily; after 2 days increase to 25 mg once daily; if needed, increase every 2 weeks up to 50 mg/day (single or divided doses). Elderly: 12.5 mg/day may be sufficient.

Angina pectoris: First 2 days: 12.5 mg twice daily; then 25 mg twice daily. Elderly: Max 50 mg/day in divided doses.

Heart Failure (Immediate release): Initial 3.125 mg twice daily (with food); increase every 2 weeks to 6.25 mg, then 12.5 mg, then 25 mg twice daily. <85 kg: Max 25 mg twice daily; ≥85 kg: Max 50 mg twice daily.

Heart Failure (Extended release): 10 mg/day; maintain for 1-2 weeks; increase to 20, 40, or 80 mg/day as needed.

Post-MI LV Dysfunction: 3.125-6.25 mg twice daily; increase after 3-10 days to 12.5 mg twice daily, then to 25 mg twice daily (target).

Extended release (Post-MI): 10-20 mg/day; increase every 3-10 days up to 80 mg/day.

Renal impairment: No dosage adjustment needed.

Hepatic impairment: Contraindicated in severe impairment; caution required.

Children: Safety and efficacy not established.

Elderly: Start with lower doses.

Common side effects: Postural hypotension, dizziness, headache, fatigue, gastrointestinal disturbances, bradycardia.

Uncommon: Diminished peripheral circulation, peripheral edema, painful extremities, dry mouth, dry eyes, eye irritation or disturbed vision, impotence, micturition disturbances, influenza-like symptoms, angina, AV block, exacerbation of intermittent claudication or Raynaud's phenomenon, allergic skin reactions, exacerbation of psoriasis, nasal stuffiness, wheezing, depressed mood, sleep disturbances, paresthesia, heart failure, changes in liver enzymes, thrombocytopenia, leukopenia.

Avoid driving or activities requiring concentration until you know how this medicine affects you.

• Take with food (improves absorption and reduces hypotension).
• Monitor clinical status for 2-3 hours after initiation and after each dose increase; ensure renal function and heart failure are not deteriorating before increasing dose.
• Do not stop abruptly (may cause sudden rise in blood pressure, increasing risk of heart attack and stroke).
• May cause dizziness or sleepiness; know your response before driving.
• Avoid alcohol consumption (may worsen side effects).
• Contraindicated in severe hepatic impairment; caution in liver disease.
• Caution during pregnancy and lactation (Category C).
• Regular blood pressure monitoring is recommended.

• Hypersensitivity
• Decompensated heart failure (requiring IV inotropic therapy)
• Bronchial asthma or related bronchospastic conditions
• Second or third degree AV block
• Sick sinus syndrome (unless permanent pacemaker is in place)
• Cardiogenic shock
• Severe bradycardia
• Severe hepatic impairment

• Rifampin: Decreases serum levels by 60%.
• Calcium channel blockers (verapamil, diltiazem): May cause bradycardia and myocardial depression.
• Digoxin: May increase digoxin levels; monitor digoxin when initiating, adjusting, or discontinuing carvedilol.
• Insulin and antidiabetic agents: May potentiate hypoglycemic effects.
• Reserpine, MAOIs, clonidine: Increased risk of hypotension and bradycardia.
• Cyclosporine: May increase concentrations.
• Ether, cyclopropane, trichloroethylene: Increased risk of hypotension and heart failure.