CARVEDILOL

Carvedilol tablets are rapidly and extensively absorbed following oral administration, with absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism. Following oral administration, the apparent mean terminal elimination half-life of carvedilol generally ranges from 7 to 10 hours. Plasma concentrations achieved are proportional to the oral dose administered. When administered with food, the rate of absorption is slowed, as evidenced by a delay in t...

14.1 Heart Failure A total of 6,975 subjects with mild to severe heart failure were evaluated in placebo-controlled trials of carvedilol. Mild-to-Moderate Heart Failure Carvedilol was studied in 5 multicenter, placebo-controlled trials, and in 1 active-controlled trial (COMET trial) involving subjects with mild-to-moderate heart failure. Four US multicenter, double-blind, placebo-controlled trials enrolled 1,094 subjects (696 randomized to carvedilol) with NYHA class II-III heart failure and ejection fraction less than or equal to 0.35. The vast majority were on digitalis, diuretics, and an AC...

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. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditio...

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...

Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. ( 5.1 ) Bradycardia, hypotension, worsening heart failure/fluid retention may occur. Reduce the dose as needed. ( 5.2 , 5.3 , 5.4 ) Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema): Avoid β-blockers. ( 4 ) However, if deemed necessary, use with caution and at lowest effective dose. ( 5.5 ) Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor ( 5.6 ) 5.1...

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 decr...