Vedilol

Approved Indications:

• Heart Failure
  • Management of mild-to-severe chronic heart failure (NYHA Class II–IV) of ischemic or cardiomyopathic origin, in combination with ACE inhibitors, diuretics, and digitalis as appropriate.
  • Reduces mortality and hospitalization risk.
• Hypertension (Essential)
  • Management of primary hypertension as monotherapy or in combination with other antihypertensive agents, particularly thiazide diuretics.
  • Effective in adults and may be used off-label in pediatrics under supervision.
• Post-Myocardial Infarction (MI) with Left Ventricular Dysfunction
  • Reduces cardiovascular mortality in patients who are clinically stable following an acute MI and have evidence of left ventricular systolic dysfunction.

Important Off-label / Clinically Accepted Uses:

• Portal Hypertension & Esophageal Varices (especially in cirrhosis)
  • Used to lower portal venous pressure and reduce variceal bleeding risk.
• Tachyarrhythmias
  • Off-label use in rate control of atrial fibrillation or atrial flutter, especially in heart failure patients.
• Migraine Prophylaxis
  • Occasionally used as an off-label beta-blocker alternative for migraine prevention.

Adults:

• Heart Failure (Chronic, NYHA II–IV):
  • Initial: 3.125 mg twice daily for 2 weeks.
  • Titrate gradually every 2 weeks to 6.25 mg, 12.5 mg, then 25 mg twice daily (max: 50 mg/day).
  • Patients <85 kg: Target 25 mg BID; ≥85 kg: up to 50 mg BID.
• Hypertension:
  • Initial: 6.25 mg twice daily.
  • Titrate every 1–2 weeks to 12.5–25 mg twice daily (max: 50 mg/day).
• Post-MI with LV Dysfunction:
  • Initial: 6.25 mg twice daily, increase to 12.5 mg BID after 3–10 days, then to 25 mg BID if tolerated.

Pediatrics: (off-label)

• Start with low doses (e.g., 0.05–0.2 mg/kg/day), titrate slowly. Specialist supervision required.

Elderly:

• Dose titration should be slower; start at lower doses to avoid hypotension or bradycardia.

Hepatic Impairment:

• Contraindicated in patients with severe hepatic impairment due to extensive liver metabolism.

Renal Impairment:

• No initial adjustment usually required; monitor for hypotension.

Administration Route:

• Oral, with food to reduce the risk of orthostatic hypotension.

Carvedilol is a non-selective beta-adrenergic blocker (β1 and β2) and alpha-1 adrenergic blocker. Its beta-blockade reduces heart rate, myocardial contractility, and sympathetic stimulation, which decreases cardiac workload. The alpha-1 blockade induces peripheral vasodilation, reducing systemic vascular resistance and lowering blood pressure. Additionally, Carvedilol exhibits antioxidant properties and suppresses oxygen free radical production in cardiac tissue. These combined actions make it especially effective in treating heart failure by improving left ventricular function and reducing mortality.

• Absorption: Rapid; bioavailability ~25–35% (first-pass metabolism).
• Onset of Action: 1–2 hours (peak effect for BP).
• Distribution: Widely distributed; >98% protein-bound.
• Metabolism: Extensive hepatic metabolism via CYP2D6, CYP2C9, CYP3A4, and others.
• Metabolites: Several active metabolites with weaker beta-blocking activity.
• Half-life: 7–10 hours (longer in poor metabolizers).
• Excretion:
  • Biliary and fecal (major)
  • Renal (minor: ~16%)

• Pregnancy:
  • FDA Category C (older system): Risk not ruled out.
  • Animal studies show adverse effects; no adequate human data. Use only if benefits justify potential risks.
• Lactation:
  • Unknown whether Carvedilol is excreted in human breast milk.
  • Due to potential for serious adverse reactions in infants (e.g., bradycardia, hypotension), caution is advised or breastfeeding should be avoided.

• Primary Class: Beta-Adrenergic Blocking Agent (Beta-Blocker)
• Subclass: Non-selective Beta Blocker with Alpha-1 Blocking Activity
• Generation: Third-generation beta-blocker

• Known hypersensitivity to Carvedilol or any excipients
• Severe hepatic impairment
• Clinically significant bradycardia or heart block (second or third degree without pacemaker)
• Cardiogenic shock or decompensated heart failure requiring IV inotropes
• Asthma or bronchospastic conditions (due to β2 blockade)
• Sick sinus syndrome (without pacemaker)

• Bradycardia and AV Block: Monitor heart rate; discontinue if significant conduction defects occur.
• Hypotension/Syncope: May cause postural hypotension; advise patients to take with food.
• Bronchospasm: Avoid in patients with reactive airway diseases.
• Diabetes Mellitus: May mask hypoglycemic symptoms (e.g., tachycardia); monitor blood glucose.
• Heart Failure Worsening: Temporary worsening may occur during dose titration; monitor closely.
• Withdrawal: Gradual tapering over 1–2 weeks is recommended to avoid rebound tachycardia or ischemia.
• Surgery/Anesthesia: Use caution due to negative inotropic effects.
• Liver Function: Monitor transaminases in patients with hepatic risk.

Common (≥1%):

• Cardiovascular: Bradycardia, hypotension, dizziness, fatigue
• Central Nervous System: Drowsiness, headache
• Gastrointestinal: Diarrhea, nausea
• Respiratory: Nasal congestion

Less Common / Serious:

• Worsening heart failure
• AV block, syncope
• Bronchospasm
• Hyperglycemia or hypoglycemia (in diabetics)
• Hepatic dysfunction (rare transaminase elevation)

Rare but Severe:

• Stevens-Johnson syndrome
• Anaphylaxis
• Severe bradyarrhythmia

• CYP Enzyme Inhibitors (e.g., Fluoxetine, Cimetidine): May increase carvedilol levels.
• CYP Inducers (e.g., Rifampin, Phenobarbital): May reduce efficacy.
• Calcium Channel Blockers (e.g., Verapamil, Diltiazem): Risk of bradycardia and AV block.
• Clonidine: Risk of rebound hypertension if both withdrawn abruptly.
• Digoxin: Carvedilol may increase digoxin plasma levels; monitor.
• Insulin/Oral Hypoglycemics: Enhanced hypoglycemic effect and masked symptoms.
• Anesthetics: Additive negative inotropic and hypotensive effects.

• Latest Heart Failure Guidelines (e.g., ACC/AHA/ESC):
  Carvedilol remains a cornerstone beta-blocker for heart failure with reduced ejection fraction (HFrEF), improving both symptoms and survival.
• Labeling Updates:
  Emphasis on titration schedules and hepatic contraindications has been reinforced in recent label revisions.
• Clinical Trials:
  Long-term outcome studies continue to validate its superiority over beta-1 selective blockers in specific heart failure populations.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15–30°C.
• Humidity & Light: Protect from moisture and light.
• Handling:
  • Keep in tightly closed containers.
  • Store away from children.
  • Do not use tablets with visible deterioration.