What are the potential side effects of Coreg (carvedilol) in an adult patient with a history of cardiovascular disease, such as high blood pressure or heart failure?

Side Effects of Coreg (Carvedilol)

Most Common Side Effects

Carvedilol causes dizziness, hypotension, bradycardia, and fatigue as its most frequent adverse effects, with dizziness occurring in 5-6% of hypertensive patients and increasing with higher doses. 1

Cardiovascular Side Effects

• Hypotension and postural hypotension occur commonly, with postural hypotension leading to discontinuation in 1% of hypertensive patients (versus 0% with placebo) 1
• Bradycardia occurs in 2% of hypertensive patients, which is expected given carvedilol's beta-blocking properties 1
• Peripheral edema occurs in 1% of patients 1
• Syncope can occur during initiation, requiring patients to avoid driving or hazardous tasks until stable 1
• Peripheral ischemia and tachycardia occur in 0.1-1% of patients 1

Central Nervous System Effects

• Dizziness is dose-dependent, increasing from 2% at 6.25 mg daily to 5% at 50 mg daily 1
• Insomnia occurs in 2% of patients 1
• Depression, impaired concentration, abnormal thinking, and emotional lability occur in 0.1-1% of patients 1
• Headache and fatigue are reported but occur at rates equal to or less than placebo 1

Gastrointestinal Effects

• Diarrhea occurs in 2% of patients 1
• Nausea and gastrointestinal pain occur in 1-3% of patients 1
• Dry mouth occurs in less than 1% of patients 1

Serious and Life-Threatening Side Effects

Respiratory Complications

• Bronchospasm is a serious risk, particularly in patients with asthma or chronic obstructive pulmonary disease, as carvedilol is a non-selective beta-blocker that blocks beta-2 receptors 1, 2
• Carvedilol is absolutely contraindicated in patients with active asthma due to risk of severe and potentially fatal bronchoconstriction 3, 2
• Interstitial pneumonitis has been reported in post-marketing surveillance 1

Cardiac Complications

• Worsening heart failure or fluid retention may occur during up-titration, requiring increased diuretics and temporary dose reduction 1
• Complete AV block and bundle branch block occur in less than 0.1% of patients 1
• Myocardial ischemia can occur, particularly in patients with Prinzmetal's variant angina 1

Hepatic Effects

• Reversible elevations in liver transaminases (ALT/AST) occur at rates similar to placebo in most trials, but confirmed hepatotoxicity with rechallenge has been documented 1
• Increased hepatic enzymes led to discontinuation in 0.2% of hypertensive patients and 0.4% of heart failure patients 1

Renal Effects

• Deterioration of renal function rarely occurs, particularly in patients with systolic blood pressure less than 100 mmHg, ischemic heart disease, diffuse vascular disease, or underlying renal insufficiency 1
• Renal function typically returns to baseline when carvedilol is stopped 1

Metabolic and Endocrine Effects

Diabetes-Related Concerns

• Carvedilol may mask hypoglycemic symptoms, particularly tachycardia, in diabetic patients receiving insulin or oral hypoglycemic agents 1
• Non-selective beta-blockers like carvedilol can potentiate insulin-induced hypoglycemia and delay recovery of serum glucose 1
• However, in well-controlled type 2 diabetes with mild-to-moderate hypertension, carvedilol had no adverse effect on glycemic control based on HbA1c measurements 1

Other Metabolic Effects

• Hypertriglyceridemia occurs in 1% of patients 1
• Hypokalemia has been reported 1
• Gout occurs in 1-3% of patients 1

Hematologic Side Effects

• Thrombocytopenia occurs in 1% of patients 1
• Anemia and leukopenia occur in less than 1% of patients 1
• Aplastic anemia has been reported in post-marketing surveillance 1

Severe Allergic and Immunologic Reactions

• Anaphylactic reactions, angioedema, and urticaria have been reported post-marketing 1
• Patients with a history of severe anaphylactic reactions may be more reactive to allergens while taking beta-blockers and may be unresponsive to usual doses of epinephrine 1
• Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported 1

Special Population Considerations

Women

• Women experience 50-100% higher drug exposure due to higher oral bioavailability, lower volume of distribution, and slower clearance via CYP2D6 4
• This may result in more pronounced side effects in female patients 5

Elderly Patients

• Postural dizziness is the major adverse effect in elderly patients 2
• Elderly patients are at higher risk for bradycardia with rate-slowing medications due to decreased baroreceptor response 6

Rare but Important Side Effects (≤0.1%)

• Cerebrovascular accident occurs in 1-3% of post-MI patients 1
• Convulsions, migraine, and neuralgia 1
• Urinary incontinence and increased micturition frequency 1
• Decreased libido in males 1
• Photosensitivity reactions, pruritus, and various rashes 1
• Tinnitus and decreased hearing 1

Drug-Specific Warnings

Surgical Considerations

• Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients treated with carvedilol due to its alpha-1 blocking properties 1
• Carvedilol should not be routinely withdrawn before major surgery, but the impaired cardiac response to reflex adrenergic stimuli may increase surgical risks 1

Other Specific Warnings

• In pheochromocytoma, an alpha-blocking agent should be initiated before any beta-blocker, and carvedilol should be used with extreme caution 1
• Thyrotoxicosis symptoms may be masked, and abrupt withdrawal can precipitate thyroid storm 1
• Peripheral vascular disease symptoms may be precipitated or aggravated 1

Discontinuation Rates

• Overall discontinuation rates due to adverse events are similar to placebo (4.9% versus 5.2% in hypertension trials) 1
• In post-MI patients with left ventricular dysfunction, hypotension was the only cause of discontinuation greater than 1% (1.5% versus 0.2% with placebo) 1