Coreg
Coreg (carvedilol)
Generic Name
Coreg (carvedilol)
Mechanism
Coreg (carvedilol) is a non‑selective β‑adrenergic blocker with additional α₁‑blocking activity and antioxidant properties.
• β‑blockade: ↓ heart rate, myocardial contractility, and renin release.
• α₁‑blockade: ↓ systemic vascular resistance → vasodilatory effect, lowering afterload.
• Antioxidant: scavenges reactive oxygen species, reducing cardiac remodeling.
Combined, these actions decrease myocardial oxygen demand, improve cardiac output, and attenuate adverse neurohumoral activation in heart failure.
Pharmacokinetics
| Parameter | Approximate Value | Notes |
| Absorption | Oral bioavailability ~25–40 % | First‑pass hepatic metabolism; food slows but does not change extent. |
| Distribution | Volume of distribution ~4 L/kg | Highly lipophilic; crosses the blood‑brain barrier. |
| Metabolism | Hepatic CYP2D6, CYP2C9, CYP3A4 → inactive metabolites | Strong inhibitors/inducers (e.g., quinidine, rifampin) alter exposure. |
| Elimination | Biliary excretion; renal excretion minimal | Half‑life 7–10 h; dose adjustment not required in mild–moderate renal impairment. |
Indications
- Chronic heart failure (HF) – Class I: reduces mortality, hospitalizations, and improves NYHA functional class when added to ACEI/ARB + diuretic.
- Hypertension – Class IIb: used alone or with diuretics/potassium‑sparing agents.
- Post‑myocardial infarction (MI) cardiomyopathy – Class IIa: improves survival when combined with other guideline‑directed therapy.
- Secondary prevention of HF in type 2 diabetes – emerging evidence in early LV dysfunction.
Contraindications
- Absolute contraindications:
- Severe bradycardia, sinus node dysfunction, second‑/third‑degree AV block without pacemaker.
- Decompensated heart failure or cardiogenic shock.
- Acute severe asthma or COPD flare.
- Warnings:
- Beta‑blocker hypersensitivity.
- Uncontrolled hyperthyroidism (symptoms may worsen).
- Pulmonary hypertension with right‑heart failure (possible right‑ventricular depression).
- Concurrent use of strong CYP3A4 inhibitors (e.g., ketoconazole) may increase carvedilol exposure → hypotension, bradycardia.
- Diabetes – masked hypoglycemia symptoms.
Dosing
| Condition | Starting Dose | Titration | Max Daily Dose | Formulation |
| HF / Post‑MI | 3.125 mg PO BID | ↑ every 2–4 wk to 6.25 mg BID → 12.5 mg BID → 25 mg BID | 25 mg BID (50 mg/day) | Immediate‑release tablets (25/50 mg). |
| Hypertension | 3.125 mg PO BID | ↑ every 4–6 wk | 25 mg BID | Same as above. |
| Age ≥ 80 yr | 3.125 mg PO BID | ↑ cautiously (≥ 8 wk intervals) | 12.5 mg BID | Same. |
• Administration: Take with or without food; avoid alcohol.
• Transitioning: Switch from other β‑blockers gradually over 3–5 days to avoid withdrawal.
• Missed dose: Skip; do not double.
Adverse Effects
Common (≥1 %):
• Bradycardia, fatigue, dizziness, hypotension, constipation, cold extremities, erectile dysfunction, sleep disturbances, nasal congestion.
Serious (≥0.1 %):
• Heart failure exacerbation (rare if titrated slowly).
• Hypotension leading to syncope.
• Bronchospasm in asthmatics.
• Hypoglycemia signs in diabetics.
• Skin rash / photosensitivity (rare).
Monitoring
- Vital signs: HR, BP (lying & standing), especially during titration.
- Cardiac: ECG for HR, PR interval, QRS; troponin if MI.
- Renal/hepatic: CBC, ALT/AST, bilirubin monthly if liver disease.
- Metabolic: Fasting glucose, HbA1c if diabetic; lipid profile quarterly.
- Fluid status: Weight, edema, BNP/NT‑proBNP trend after initiation.
- Adverse effect diary: Record dizziness, syncope, bronchospasm, sleep issues.
Clinical Pearls
- Start Low, Go Slow: Even in stable HF, a two‑week interval between dose uptitrations reduces risk of decompensation.
- Food Interaction: A high‑fat meal delays peak plasma levels by ~1 h but does not alter bioavailability—use flexibility to improve tolerance.
- Alpha‑1 Blockade Matters: Carvedilol’s α₁ action confers unique vasodilatory benefit, explaining its superior survival edge over β‑selective blockers in some trials (e.g., CIBIS‑II).
- Diabetic Patients: Monitor capillary glucose thrice daily when initiating or uptitrating; insulin or sulfonylurea adjustment may be needed.
- Drug‑Drug Interactions: Avoid concomitant use with potent CYP3A4 inhibitors; consider dose reduction or switch to alternative β‑blockers.
- Post‑MI Use: Carvedilol monotherapy at 6.25 mg BID (12.5 mg/day) reduces the risk of recurrent MI and improves LV remodeling up to 12‑month.
- Right‑Heart Failure Caution: In pulmonary arterial hypertension, use with caution; consider switching to β‑selective blocker without α‑blockade if RV dysfunction is predominant.
Key Takeaway:
Carvedilol is a multifunctional β‑/α‑blocker that uniquely improves survival in heart failure and post‑MI populations. Mastering its titration schedule, monitoring protocol, and interaction profile ensures optimal therapeutic benefit while minimizing adverse events.