Carvedilol is an antihypertensive belonging to a class of beta-adrenoreceptor antagonists.
Class:
Beta-adrenoreceptor antagonist (nonselective beta-blocker with selective alpha-1 blockade)
Presentation
- Tablets: 6.25 mg, 12.5 mg, 25 mg
Mechanism of Action
- Nonselectively blocks beta-1 (myocardium) and beta-2 (bronchial and vascular smooth muscle) adrenergic receptors
- Selective alpha-1 adrenergic receptor blockade causing vasodilation
- Does not have intrinsic sympathomimetic activity (no beta-agonist effects)
- Weak membrane-stabilizing effects
Pharmacokinetics
- Well absorbed orally but extensive first-pass hepatic metabolism → bioavailability ~25%
- Peak plasma concentration: 1–2 hours post-dose
- Highly lipophilic, >98% plasma protein bound
- Metabolized primarily by hepatic CYP450 enzymes CYP2D6 and CYP2C9
- Excretion mainly via bile
- Elimination half-life: 6–10 hours
Indications
- Hypertension
- Angina pectoris
- Symptomatic heart failure (adjunct therapy)
- Reduce mortality post-myocardial infarction in left ventricular dysfunction
Dosage
Hypertension:
- Initial: 12.5 mg once daily (or 6.25 mg once daily)
- Titrate to 25 mg once daily after 2 days, or 12.5 mg twice daily after 1–2 weeks
- Maximum: 50 mg daily (divided doses)
- Elderly: 12.5 mg once daily usually sufficient
Angina Pectoris:
- Initial: 12.5 mg twice daily
- Increase to 25 mg twice daily after 2 days
Heart Failure:
- Initial: 3.125 mg twice daily with food (to minimize hypotension risk)
- Titrate to 6.25 mg twice daily, then gradually increase every ≥2 weeks to max tolerated dose
- Max dose:
- 25 mg twice daily (severe HF or <85 kg body weight)
- 50 mg twice daily (mild to moderate HF and >85 kg)
Contraindications and Precautions
- Bradycardia (reduce dose if HR < 55 bpm)
- Hypotension and syncope risk — administer with food and start at low doses
- Pheochromocytoma: alpha-1 blocker must precede beta-blocker use to avoid unopposed alpha stimulation
Adverse Effects
- Cardiovascular: Bradycardia, hypotension, precipitate heart failure or heart block in susceptible patients
- CNS: Headache, confusion, hallucinations, sleep disturbances, fatigue
- Neuromuscular: Paresthesia, peripheral neuropathy, arthralgia, myopathies
- Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal cramps
