Is carvedilol (beta-blocker) significantly removed by dialysis in patients with impaired renal function?

Carvedilol Is Not Removed by Dialysis

Carvedilol is not dialyzable and is not significantly removed by hemodialysis due to its high protein binding and lipophilic properties. 1, 2

Pharmacokinetic Properties of Carvedilol

• Carvedilol is classified as "not dialyzable" according to the EXTRIP workgroup's systematic review and recommendations 1
• It is a highly lipophilic compound with strong plasma protein binding (>98%), primarily to albumin, which prevents its removal during dialysis 2
• Carvedilol is primarily metabolized by the liver and excreted via the biliary system, with less than 2% excreted unchanged in urine 2, 3
• The drug has a steady-state volume of distribution of approximately 115 L, indicating substantial distribution into extravascular tissues 2

Evidence for Non-Dialyzability

• When measured from dialysate collection during hemodialysis, the amount of carvedilol removed was approximately 0% of the ingested dose 1
• Modern high-flux hemodialysis studies confirm carvedilol's negligible dialytic clearance of only 0.2 ml/min using the recovery clearance method 4
• Even using the arterial-venous difference method, carvedilol's dialytic clearance was only 24 ml/min, which is minimal compared to other beta-blockers 4
• Multiple studies in hemodialysis patients have shown no elimination of carvedilol during dialysis sessions 3, 5

Clinical Implications

• No dosage adjustments are needed for carvedilol on dialysis days versus non-dialysis days 6, 5
• Pharmacokinetic parameters of carvedilol are not influenced by intermittent hemodialysis, and there is no accumulation of the drug or its active metabolites in dialysis patients 3, 6
• The plasma concentration profile of carvedilol remains similar on both dialysis and non-dialysis days 5

Comparison with Other Beta-Blockers

• Unlike carvedilol, other beta-blockers such as atenolol, metoprolol, and bisoprolol are significantly removed by dialysis 1, 4
• Dialytic clearance values (ml/min) using recovery clearance method: atenolol (72), metoprolol (87), bisoprolol (44) versus carvedilol (0.2) 4
• This difference in dialyzability may have clinical implications for blood pressure control and cardiovascular protection during dialysis 1

Considerations for Use in Dialysis Patients

• When selecting beta-blockers for dialysis patients, consider that non-dialyzable agents like carvedilol maintain their therapeutic effect throughout dialysis 1
• However, some retrospective studies suggest higher mortality rates with non-dialyzable carvedilol versus dialyzable metoprolol, possibly due to increased risk of intradialytic hypotension 1
• For patients with frequent intradialytic hypotension, it may be prudent to avoid non-dialyzable medications like carvedilol 1
• For patients with stable intradialytic blood pressure, carvedilol's longer-acting properties may improve adherence and reduce pill burden 1

Dosing Considerations

• Despite renal impairment, studies show that dosage adjustments are generally not required for carvedilol in dialysis patients 6, 7
• Plasma concentrations of carvedilol are approximately 40-50% higher in patients with renal impairment compared to those with normal renal function, but this is modest given the large interindividual variability 2, 7
• The timing of carvedilol administration should be individualized based on interdialytic blood pressure patterns and frequency of intradialytic hypotension 1

In conclusion, carvedilol is not removed by dialysis and maintains its therapeutic effect throughout the dialysis session, which can be advantageous for maintaining cardiovascular protection but may increase the risk of intradialytic hypotension in susceptible patients.