Carvedilol Formulations: Extended Release and Immediate Release
Yes, carvedilol is available in both extended-release (CR) and immediate-release (IR) formulations, with the extended-release version allowing for once-daily dosing compared to twice-daily dosing for the immediate-release version. 1
Formulation Characteristics
- Carvedilol IR requires twice-daily dosing with a usual dose range of 3.125-50 mg twice daily 1
- Carvedilol CR (controlled-release/extended-release) allows for once-daily dosing with a usual dose range of 10-80 mg once daily 1
- Carvedilol CR is specifically listed in clinical guidelines as "Carvedilol phosphate" with a dosing range of 20-80 mg once daily 1
Pharmacokinetic Properties
- Both formulations contain the same active ingredient (carvedilol), which is a racemic mixture of R(+) and S(-) enantiomers that combines beta₁-, beta₂-, and alpha₁-adrenoceptor blockade 2
- Carvedilol CR delays the time to maximum plasma concentration (Cmax) by approximately 3.5 hours compared to the IR formulation, consistent with its extended-release properties 2
- Despite the difference in release profile, both formulations demonstrate equivalent area under the curve (AUC), indicating similar overall drug exposure 2, 3
Clinical Equivalence
- Studies have demonstrated that the pharmacokinetic profiles of both formulations are equivalent at steady state, with the following dose correspondences 4:
- Carvedilol IR 3.125 mg twice daily = Carvedilol CR 10 mg once daily
- Carvedilol IR 6.25 mg twice daily = Carvedilol CR 20 mg once daily
- Carvedilol IR 12.5 mg twice daily = Carvedilol CR 40 mg once daily
- Carvedilol IR 25 mg twice daily = Carvedilol CR 80 mg once daily
Clinical Applications
- Both formulations are indicated for the treatment of hypertension, heart failure, and left ventricular dysfunction following myocardial infarction 2, 4
- Carvedilol is classified as a non-cardioselective beta-blocker with combined alpha- and beta-receptor blocking properties 1
- Carvedilol CR was developed to improve treatment adherence through once-daily dosing while maintaining the same clinical benefits as the twice-daily IR formulation 5
Safety Considerations
- The safety profile is similar between both formulations, though some studies suggest fewer adverse events with the CR formulation compared to the IR formulation 2
- Common side effects include dizziness and headache, which were reported less frequently with the CR formulation in comparative studies 2
- Both formulations carry the same precaution against abrupt discontinuation, which can lead to rebound hypertension or worsening of cardiac conditions 1
Practical Considerations
- The availability of both formulations allows for individualized dosing based on patient needs and preferences, with the CR formulation potentially improving adherence through simplified once-daily dosing 5, 3
- Carvedilol CR is preferred in patients with heart failure with reduced ejection fraction (HFrEF) due to its convenient dosing schedule 1
- For patients transitioning between formulations, the appropriate dose conversion should be followed to maintain therapeutic equivalence 4