CARVEDILOL PHOSPHATE

AbsorptionCarvedilol is rapidly and extensively absorbed following oral administration of immediate-release carvedilol tablets, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism. Carvedilol phosphate extended-release capsules have approximately 85% of the bioavailability of immediate-release carvedilol tablets. For corresponding dosages [see Dosage and Administration (2) ] , the exposure (AUC, C max , trough concentration) of carve...

Support for the use of carvedilol phosphate extended-release capsules for the treatment of mild-to-severe heart failure and for patients with left ventricular dysfunction following myocardial infarction is based on the equivalence of pharmacokinetic and pharmacodynamic (beta 1 -blockade) parameters between carvedilol phosphate extended-release capsules and immediate-release carvedilol [see Clinical Pharmacology (12.2 , 12.3) ] . The clinical trials performed with immediate-release carvedilol in heart failure and left ventricular dysfunction following myocardial infarction are presented below. ...

The safety profile of carvedilol phosphate extended-release capsules were similar to that observed for immediate-release carvedilol. Most common adverse events seen with immediate-release carvedilol. ( 6.1 ): Heart failure and left ventricular dysfunction following myocardial infarction (greater than or equal to 10%): Dizziness, fatigue, hypotension, diarrhea, hyperglycemia, asthenia, bradycardia, weight increase. Hypertension (greater than or equal to 5%): Dizziness. To report SUSPECTED ADVERSE...

Carvedilol phosphate extended-release capsules are contraindicated in the following conditions: Bronchial asthma or related bronchospastic conditions. Deaths from status asthmaticus have been reported following single doses of immediate-release carvedilol. Second- or third-degree AV block. Sick sinus syndrome. Severe bradycardia (unless a permanent pacemaker is in place). Patients with cardiogenic...

In clinical trials of extended-release carvedilol phosphate capsules in subjects with hypertension (338 subjects) and in subjects with left ventricular dysfunction following a myocardial infarction or heart failure (187 subjects), the profile of adverse events observed with carvedilol phosphate was generally similar to that observed with the administration of immediate-release carvedilol. Therefore, the information included within this section is based on data from controlled clinical trials wit...

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. ( 7.2 ) Cyclosporine or digoxin levels may increase. ( 7.3 , 7.4 ) Both digitalis glycosides and beta-blockers slow atrioventricular conduction and d...