Overview
11 DESCRIPTION Carvedilol is a nonselective β-adrenergic blocking agent with α 1 -blocking activity. It is (±)-1-(Carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol. Carvedilol is a racemic mixture with the following structure: Carvedilol, USP is a white to almost white crystalline powder with a molecular weight of 406.5 and a molecular formula of C 24 H 26 N 2 O 4 .
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Carvedilol is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α 1 -adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. 12.2 Pharmacodynamics Heart Failure The basis for the beneficial effects of carvedilol tablets in heart failure is not established. Two placebo-controlled trials compared the acute hemodynamic effects of carvedilol tablets with baseline measurements in 59 and 49 subjects with NYHA class II-IV heart failure receiving diuretics, ACE inhibitors, and digitalis.
Indications
- 1 INDICATIONS AND USAGE Carvedilol tablets are an alpha/beta-adrenergic blocking agent indicated for the treatment of: mild to severe chronic heart failure ( 1.1 ) left ventricular dysfunction following myocardial infarction in clinically stable patients( 1.2 ) hypertension( 1.3 ) 1.1 Heart Failure Carvedilol tablets are indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see Drug Interactions ( 7.
Common Doses
- 3.125 mg
- 25 mg
- 6.25 mg
- 12.5 mg
Dosage
2 DOSAGE AND ADMINISTRATION Take with food. Individualize dosage and monitor during up-titration. ( 2 ) Heart failure: Start at 3.125 mg twice daily and increase to 6.25, 12.5, and then 25 mg twice daily over intervals of at least 2 weeks. Maintain lower doses if higher doses are not tolerated. ( 2.1 ) Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then 25 mg twice daily after intervals of 3 to 10 days. A lower starting dose or slower titration may be used.( 2.2 ) Hypertension: Start at 6.
Contraindications
- 4 CONTRAINDICATIONS Bronchial asthma or related bronchospastic conditions. ( 4 ) Second- or third-degree AV block. ( 4 ) Sick sinus syndrome. ( 4 ) Severe bradycardia (unless permanent pacemaker in place). ( 4 ) Patients in cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy. ( 4 ) Severe hepatic impairment. ( 2.4 , 4 ) History of serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvedilol.
Side Effects
- 6 ADVERSE REACTIONS Most common adverse events ( 6.1 ): Heart failure and left ventricular dysfunction following myocardial infarction (≥10%): Dizziness, fatigue, hypotension, diarrhea, hyperglycemia, asthenia, bradycardia, weight increase. Hypertension (≥5%): Dizziness. To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1- 877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS CYP P450 2D6 enzyme inhibitors may increase and rifampin may decrease carvedilol levels. ( 7.1 , 7.5 ) Hypotensive agents (e.g., reserpine, MAO inhibitors, clonidine) may increase the risk of hypotension and/or severe bradycardia. ( 7.4 ) Cyclosporine or digoxin levels may increase. ( 7.3 , 7.4 ) Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. ( 7.4 ) Amiodarone may increase carvedilol levels resulting in further slowing of the heart rate or cardiac conduction. ( 7.