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 contraindicated in asthma patients due to carvedilol's non-selective beta-2 blockade, which can cause severe and sometimes fatal bronchoconstriction 2, 1, 3
• In patients with chronic obstructive pulmonary disease or emphysema, carvedilol should be used with extreme caution at the smallest effective dose 1
• 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 rarely 1

Metabolic and Endocrine Effects

• Carvedilol may mask hypoglycemia symptoms (particularly tachycardia) and delay recovery of serum glucose in diabetic patients receiving insulin or oral hypoglycemic agents 1
• Hypertriglyceridemia occurs in 1% of patients 1
• Hypokalemia can occur 1
• Beta-blockade may mask clinical signs of hyperthyroidism, and abrupt withdrawal may precipitate thyroid storm 1

Hepatic Effects

• Reversible elevations in serum transaminases (ALT or AST) occur at rates similar to placebo, but confirmed elevations (2-3 times upper limit of normal) have been observed with rechallenge 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 low blood pressure (systolic <100 mmHg), ischemic heart disease, diffuse vascular disease, or underlying renal insufficiency 1
• Renal function typically returns to baseline when carvedilol is stopped 1

Rare but Important Side Effects

Hematologic

• Thrombocytopenia occurs in 1% of patients 1
• Anemia and leukopenia occur in 0.1-1% of patients 1
• Aplastic anemia and pancytopenia have been reported in post-marketing surveillance 1

Allergic and Immunologic

• Anaphylactic reactions are more severe in patients with a history of severe anaphylaxis, as beta-blockers make patients unresponsive to usual doses of epinephrine 1
• Hypersensitivity reactions including angioedema and urticaria have been reported 1

Dermatologic

• Pruritus and various rashes (erythematous, maculopapular, psoriasiform) occur in 0.1-1% of patients 1
• Photosensitivity reactions occur 1
• Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported in post-marketing surveillance 1

Genitourinary

• Decreased libido occurs in 0.1-1% of male patients 1
• Urinary incontinence has been reported in post-marketing surveillance 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 requiring lower doses 4

Elderly Patients

• Postural dizziness is the major adverse effect in elderly patients, requiring careful dose titration 3
• Elderly patients have decreased baroreceptor response, increasing bradycardia risk 5

Patients with Heart Failure

• In the CAPRICORN trial of post-MI patients with left ventricular dysfunction, flu syndrome, cerebrovascular accident, peripheral vascular disorder, hypotonia, depression, gastrointestinal pain, arthritis, and gout occurred in 1-3% of patients more frequently than placebo 1
• Hypotension was the only discontinuation cause exceeding 1% (1.5% versus 0.2% placebo) 1

Critical Drug Interactions and Contraindications

Absolute Contraindications

• Asthma or severe bronchial disease due to risk of fatal bronchospasm 2, 1, 3
• Symptomatic bradycardia or hypotension 6
• Decompensated heart failure requiring intravenous inotropic support 1

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
• Chronically administered carvedilol should not be routinely withdrawn before major surgery, but the impaired cardiac response to reflex adrenergic stimuli may increase surgical risks 1

Pheochromocytoma

• An alpha-blocking agent must be initiated before any beta-blocker in patients with pheochromocytoma, and carvedilol should be used with extreme caution despite its alpha-blocking properties 1