Should verapamil be held in patients with Chronic Kidney Disease (CKD)?

Verapamil Use in Chronic Kidney Disease

Verapamil should be used with caution in patients with chronic kidney disease (CKD) and is not recommended in patients with severe CKD due to risk of serious adverse effects including heart block, hypotension, and hyperkalemia. 1, 2, 3

Pharmacokinetics in CKD

• About 70% of verapamil is excreted as metabolites in the urine, requiring careful monitoring in patients with impaired renal function 1
• Verapamil is not removed by hemodialysis, which can lead to drug accumulation in patients with advanced CKD 1
• While some studies show similar pharmacokinetics between normal subjects and those with renal failure 4, case reports document severe toxicity in CKD patients 2, 3

Risks in CKD Patients

• Multiple case reports document serious adverse effects in CKD patients taking sustained-release verapamil, including:

  • Atrioventricular heart block 2, 3
  • Hypotension 2, 3
  • Hyperkalemia 2, 3
  • Metabolic acidosis 2
  • Hepatic dysfunction 2
  • Worsening renal function 3

• These adverse effects can occur within hours to days of starting treatment, even at recommended doses 3

Recommendations for Verapamil Use in CKD

• Verapamil should be administered cautiously to patients with impaired renal function with careful monitoring for PR interval prolongation or other signs of overdosage 1

• For patients with mild to moderate CKD who require verapamil:

  • Start with lower doses (approximately 30% of the dose given to patients with normal renal function) 1
  • Monitor closely for cardiac conduction abnormalities, blood pressure, and potassium levels 1, 2
  • Consider alternative antihypertensive agents if possible 5

• For severe CKD (eGFR <30 ml/min/1.73m²):

  • Avoid sustained-release formulations due to documented severe adverse effects 2, 3
  • Consider alternative agents with better safety profiles in CKD 5

Preferred Alternatives in CKD

• Renin-angiotensin system inhibitors (ACEIs or ARBs) are recommended as first-line therapy for hypertension in CKD, particularly in patients with albuminuria 5
• In a study of PD patients, verapamil combined with trandolapril showed no significant difference in major cardiovascular events compared to trandolapril alone 5
• For patients who cannot tolerate ACEIs/ARBs, other calcium channel blockers like amlodipine may be safer options in CKD 5

Special Considerations

• Verapamil should not be combined with beta-blockers in CKD patients due to increased risk of bradycardia and heart block 1
• Verapamil can increase serum digoxin levels by 50-75%, requiring dose adjustment and careful monitoring in digitalized patients 1
• Drug interactions are more concerning in CKD patients due to altered pharmacokinetics and reduced clearance 6

Monitoring Recommendations

• Monitor ECG for PR interval prolongation and heart block 1, 2
• Check blood pressure frequently for hypotension 2, 3
• Monitor serum potassium levels for hyperkalemia 2, 3
• Assess renal function regularly for worsening of CKD 3
• Watch for signs of hepatic dysfunction 2

While some studies suggest verapamil may have beneficial effects on renal hemodynamics in mild to moderate CKD 7, the risk of serious adverse effects in advanced CKD outweighs potential benefits, making it prudent to consider alternative agents in this population.