Carvedilol

BRAND NAMES                  

In the United States, carvedilol is marketed under the brand names Coreg and Coreg CR (extended-release), with generic versions also readily available.

MECHANISM OF ACTION

• Carvedilol is a nonselective beta-blocker that also blocks alpha-1 adrenergic receptors.

• Beta-blockade: It inhibits beta-1 and beta-2 receptors in the heart and other tissues, slowing the heart rate and reducing the force of heart contractions, which decreases cardiac workload.

• Alpha-1 blockade: It relaxes and dilates blood vessels by blocking alpha-1 receptors, improving blood flow.

• Overall effect: The combination of heart rate reduction and vascular relaxation lowers blood pressure and enhances circulation throughout the body.

PHARMACOKINETICS:

Absorption

Carvedilol is quickly and well absorbed when taken orally, reaching peak plasma levels within 1 to 2 hours. However, extensive first-pass metabolism in the liver reduces its overall bioavailability to approximately 25–35%.

Distribution

Carvedilol is a highly lipophilic drug that distributes widely into body tissues, reflected by a large volume of distribution of about 115 L (1.5 L/kg).

Metabolism

Carvedilol is primarily metabolized in the liver via oxidation, demethylation, and glucuronidation, processes mediated by various cytochrome P450 (CYP) enzymes. It exists as a racemic mixture of two enantiomers, R(+)-carvedilol and S(-)-carvedilol, which are metabolized differently and both contribute to its therapeutic effects.

Excretion

Approximately 16% of carvedilol is eliminated through the urine, with less than 2% excreted unchanged. The drug is mainly excreted via bile and feces.

PHARMACODYNAMICS

Carvedilol slows heart rate by blocking beta-adrenergic receptors and lowers blood pressure through alpha-1 adrenergic receptor antagonism. It has a long duration of action, usually allowing for once-daily dosing, with a broad therapeutic range of 10–80 mg daily. Patients should not discontinue carvedilol abruptly, as sudden withdrawal may worsen coronary artery disease.

ADMINISTRATION

Carvedilol is typically taken orally, with or immediately after meals to improve absorption and reduce the risk of low blood pressure. The dose and frequency depend on the condition being treated, patient response, and tolerability. It is important to take the medication consistently at the same time each day and not to stop it abruptly without consulting a healthcare provider, as sudden discontinuation may worsen heart conditions.

DOSAGE AND STRENGTH

Carvedilol is available in tablet form with common strengths of 3.125 mg, 6.25 mg, 12.5 mg, and 25 mg. The dosage varies depending on the condition being treated. For heart failure, treatment often starts at alow dose of 3.125 mg twice daily, gradually increasing based on tolerance. For hypertension, typical starting doses range from 6.25 mg to 12.5 mg twice daily, with adjustments made as needed. In patients with left ventricular dysfunction after a heart attack, the usual dose is 6.25 mg twice daily, titrated gradually. The exact dose and frequency should always be determined by a healthcare provider.

DRUG INTERACTIONS

Carvedilol interacts with various drugs, mainly due to its impact on blood pressure, heart rate, and its metabolism via the cytochrome P450 (CYP450) system. Combining it with medications that also lower blood pressure, reduce heart rate, or alter CYP450 activity can increase the risk of serious side effects.

FOOD INTERACTIONS

Carvedilol is a beta-blocker used to manage high blood pressure and other heart-related conditions. Grapefruit, caffeine, and alcohol may affect the absorption of beta-blockers and should be consumed with caution. Additionally, reducing salt intake is recommended to support the medication’s effectiveness.

CONTRAINDICATIONS

Carvedilol is not recommended for patients with severe or life-threatening heart or liver disorders, or for those with a known allergy to the drug. Its beta-blocking effects can aggravate certain medical conditions, potentially causing serious or fatal complications.

SIDE EFFECTS

• Dizziness or lightheadedness

• Unusual fatigue or weakness

• Slow heart rate (bradycardia)

• Diarrhea

• Weight gain (often from fluid retention)

• Dry eyes

OVER DOSE

Carvedilol overdose can be serious and potentially life-threatening. Symptoms may include severe hypotension (low blood pressure), bradycardia (slow heart rate), heart block, and bronchospasm. Management typically involves supportive care, such as monitoring vital signs, administering intravenous fluids, using medications to raise blood pressure or heart rate if necessary, and, in severe cases, employing advanced interventions like temporary pacing or mechanical support.

TOXICITY

Carvedilol toxicity is a medical emergency that primarily affects the cardiovascular system, leading to severe hypotension and bradycardia. Toxicity can result from an intentional or accidental overdose, or in susceptible individuals with compromised liver function, it can occur at standard therapeutic doses.