Do any beta blockers (beta-adrenergic blocking agents) accumulate in patients with impaired renal function?

From the Guidelines

Yes, some beta blockers do accumulate in renal failure, specifically those that are primarily eliminated by the kidneys, such as atenolol and sotalol, as indicated by the EXTRIP workgroup 1.

Key Points to Consider

• Beta blockers that are primarily eliminated by the kidneys are most affected, including atenolol, nadolol, sotalol, and acebutolol.
• These medications require dose adjustments in patients with decreased renal function to prevent toxicity.
• In contrast, beta blockers with hepatic metabolism such as metoprolol, carvedilol, propranolol, and labetalol are safer options in renal impairment as they don't significantly accumulate.
• The accumulation of renally-cleared beta blockers can lead to excessive beta-blockade, resulting in bradycardia, hypotension, bronchospasm, and hypoglycemia.

Recommendations for Clinical Practice

• When treating patients with renal failure, it's essential to select beta blockers with hepatic clearance when possible or adjust doses appropriately for renally cleared options.
• For example, atenolol dosing should be reduced by 50% when creatinine clearance is 15-35 mL/min and by 75% when clearance is less than 15 mL/min, as suggested by general clinical guidelines, although specific recommendations may vary based on the most recent evidence 1.
• The EXTRIP workgroup suggests extracorporeal treatment (ECTR) in patients severely poisoned with atenolol or sotalol, especially in the context of impaired kidney function, due to their dialyzability 1.

From the FDA Drug Label

Although Carvedilol Tablet is metabolized primarily by the liver, plasma concentrations of Carvedilol Tablet have been reported to be increased in patients with renal impairment Based on mean AUC data, approximately 40% to 50% higher plasma concentrations of Carvedilol Tablet were observed in hypertensive patients with moderate to severe renal impairment compared to a control group of hypertensive patients with normal renal function. Sotalol does not bind to plasma proteins and is not metabolized. Sotalol shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l enantiomers of sotalol are essentially identical. Sotalol crosses the blood brain barrier poorly Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary in conditions of renal impairment

Yes, some beta blockers, such as Carvedilol and Sotalol, can accumulate in renal failure.

• Carvedilol: Plasma concentrations are increased by approximately 40% to 50% in patients with moderate to severe renal impairment.
• Sotalol: Excretion is predominantly via the kidney in the unchanged form, and lower doses are necessary in conditions of renal impairment 2, 2.

From the Research

Beta Blockers and Renal Failure

• Beta blockers can affect renal function, and their use in patients with renal failure requires careful consideration 3.
• The beta blockers with low lipid solubility, such as atenolol, nadolol, and sotalol, are not metabolized and their dose must be reduced in renal failure 3.
• Propranolol has active metabolites and its dose must also be reduced slightly in uraemia 3.
• Carvedilol, a vasodilating beta blocker, may be preferable to metoprolol in patients with heart failure and renal impairment, as it may help preserve renal function 4.
• The use of beta blockers in patients with chronic kidney disease (CKD) can help reduce cardiovascular risk, but requires careful selection and dosing to minimize the risk of adverse effects 5, 6.

Accumulation of Beta Blockers in Renal Failure

• Water-soluble beta blockers, such as atenolol and metoprolol, are dialyzable and may require supplementation to avoid exacerbation of arrhythmias following dialysis 6.
• The accumulation of beta blockers in renal failure can increase the risk of adverse effects, and dose adjustments may be necessary to minimize this risk 3, 6.
• There is limited information available on the accumulation of specific beta blockers in renal failure, and further studies are needed to fully understand this issue 7.