Coreg - Drug Monograph

Introduction

Coreg (carvedilol) is a non-selective beta-adrenergic blocking agent with additional alpha-1 blocking activity, classified as a third-generation beta-blocker. It is widely used in cardiovascular medicine for its multifaceted pharmacological properties that provide both anti-adrenergic and vasodilatory effects.

Mechanism of Action

Carvedilol exerts its therapeutic effects through multiple mechanisms:

• Non-selective beta-adrenergic blockade (β₁, β₂)
• Alpha-1 adrenergic receptor blockade
• Antioxidant properties
• Antiproliferative effects

The beta-blockade reduces heart rate, myocardial contractility, and cardiac output, while alpha-1 blockade causes peripheral vasodilation, reducing peripheral vascular resistance. The combination results in decreased myocardial oxygen demand and afterload reduction.

Indications

FDA-approved indications:

• Heart failure with reduced ejection fraction (HFrEF)
• Hypertension
• Post-myocardial infarction with left ventricular dysfunction

Off-label uses:

• Stable angina pectoris
• Atrial fibrillation rate control
• Supraventricular tachycardia

Dosage and Administration

• Initial: 3.125 mg twice daily
• Titrate: Double dose every 2 weeks as tolerated
• Target: 25 mg twice daily (≤85 kg) or 50 mg twice daily (>85 kg)

• Initial: 6.25 mg twice daily
• Maintenance: 12.5-25 mg twice daily
• Maximum: 50 mg daily

• Initial: 6.25 mg twice daily
• Titrate to 25 mg twice daily

• Hepatic impairment: Use contraindicated in severe liver impairment
• Renal impairment: No dosage adjustment required
• Geriatric: Initiate with lower doses
• Pediatric: Safety not established

Pharmacokinetics

• Absorption: Rapid and complete (>90% bioavailability)
• Distribution: Extensive tissue binding, volume of distribution: 115 L
• Protein binding: >98% (primarily albumin)
• Metabolism: Extensive hepatic metabolism via CYP2D6 and CYP2C9
• Elimination: Primarily biliary/fecal excretion (60%)
• Half-life: 7-10 hours
• Time to peak: 1-2 hours

Contraindications

• Severe hepatic impairment
• Bronchial asthma or related bronchospastic conditions
• Second- or third-degree heart block
• Sick sinus syndrome without pacemaker
• Cardiogenic shock
• Decompensated heart failure requiring IV inotropic therapy
• Severe bradycardia
• Hypersensitivity to carvedilol or components

Warnings and Precautions

• Abrupt discontinuation may exacerbate angina and myocardial infarction

• Perioperative risk: Continue during surgery unless contraindicated
• Diabetes mellitus: May mask hypoglycemia symptoms
• Thyrotoxicosis: May mask clinical signs
• Peripheral vascular disease: May exacerbate symptoms
• Pheochromocytoma: Requires alpha-blockade first
• Anesthesia: Increased risk of hypotension

Drug Interactions

• CYP2D6 inhibitors (fluoxetine, paroxetine): Increased carvedilol levels
• CYP2D6 inducers (rifampin): Decreased carvedilol levels
• Other antihypertensives: Additive hypotensive effects
• Insulin/oral hypoglycemics: Enhanced hypoglycemic effects
• Digoxin: Increased digoxin levels (monitor)
• Clonidine: Rebound hypertension

Adverse Effects

• Dizziness (32%)
• Fatigue (24%)
• Hypotension (15%)
• Bradycardia (12%)
• Weight gain (11%)

• Heart block
• Bronchospasm
• Worsening heart failure
• Hepatotoxicity
• Hypersensitivity reactions

Monitoring Parameters

• Blood pressure and heart rate
• ECG
• Liver function tests
• Renal function
• Weight

• Vital signs at each dose adjustment
• Symptom assessment for heart failure
• Blood glucose in diabetics
• Signs of fluid overload
• Exercise tolerance

• Heart rate 50-60 bpm
• Systolic BP >90 mmHg
• Improved functional status
• Reduced hospitalizations

Patient Education

• Take with food to minimize orthostatic hypotension
• Do not crush or chew extended-release capsules
• Take at same times daily

• Rise slowly from sitting/lying position
• Avoid alcohol
• Monitor weight daily
• Report shortness of breath or edema

• Dizziness or lightheadedness
• Excessive fatigue
• Shortness of breath
• Weight gain >2-3 pounds/day
• Slow heart rate

• Do not stop abruptly
• Inform all healthcare providers about Coreg use
• Carry medication identification

References

1. Packer M, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22):1651-1658. 2. FDA Prescribing Information: Coreg (carvedilol) 3. Frishman WH. Carvedilol. N Engl J Med. 1998;339(24):1759-1765. 4. Heart Failure Society of America. 2010 HFSA Comprehensive Heart Failure Practice Guideline. 5. ACC/AHA Guidelines for the Management of Heart Failure (2022) 6. JNC 8 Guidelines for the Management of Hypertension (2014)