Is Diltiazem (a calcium channel blocker) contraindicated in patients with impaired renal (kidney) function?

Diltiazem is NOT contraindicated in kidney disease

Diltiazem can be safely used in patients with renal impairment without dose adjustment, as it is primarily metabolized by the liver rather than excreted by the kidneys. 1, 2

Pharmacokinetic Rationale

• Diltiazem undergoes extensive hepatic metabolism with only 2-4% of unchanged drug appearing in the urine 1
• A study in 9 patients with severely impaired renal function (GFR 0.03-0.87 mL/s/1.73 m²) demonstrated that diltiazem and its main metabolite (desacetyldiltiazem) had pharmacokinetic profiles similar to patients with normal renal function, including peak plasma concentration, half-life, and urinary excretion 2
• The FDA label states that diltiazem is extensively metabolized by the liver and excreted by the kidneys and bile, but emphasizes hepatic metabolism as the primary route 1

Clinical Use in Renal Disease

The drug should be used with caution and monitoring in patients with impaired renal function, but no specific dose reduction is required. 1

Monitoring Requirements

• Laboratory parameters of renal and hepatic function should be monitored at regular intervals during prolonged use 1
• This represents standard monitoring rather than a contraindication 1

Evidence in Renal Populations

• Diltiazem has been successfully used in uremic hemodialysis patients with diastolic dysfunction, improving symptoms and reducing intradialytic hypotension episodes without adverse effects 3
• In hypertensive patients with baseline GFR ≤80 mL/min/1.73 m², diltiazem therapy was associated with marked improvement in GFR (48%) and effective renal plasma flow (36%) 4
• Studies show diltiazem may actually have beneficial renal hemodynamic effects, including decreased renal vascular resistance 4, 5

Important Contraindications (NOT Related to Renal Disease)

Diltiazem IS contraindicated in the following cardiac conditions: 6

• Bradycardia (heart rate <50 bpm with worsening symptoms) 6
• Left ventricular dysfunction (LVD) or heart failure with reduced ejection fraction (HFrEF) 6
• Concomitant use with beta-blockers in patients with LVD due to negative inotropic effects and risk of heart block 6
• Sick sinus syndrome (diltiazem significantly prolongs sinus cycle length up to 50%) 1

Special Considerations in Renal Disease

Drug Interactions Requiring Caution

• Patients with renal and/or hepatic impairment taking other CYP450 3A4 substrates may require dosage adjustment when starting or stopping diltiazem 1
• Diltiazem has high hepatic extraction and depends primarily on hepatic blood flow for clearance, which may be reduced in elderly patients 6

Comparison with Other Calcium Channel Blockers

• Unlike diltiazem and verapamil, dihydropyridine calcium channel blockers (amlodipine, felodipine) can be added to beta-blockers in patients with heart failure 6
• Newer calcium channel blockers show neutral effects on survival when added to baseline therapy including ACE inhibitors 6

Clinical Bottom Line

Diltiazem requires hepatic dose adjustment considerations but NOT renal dose adjustment. The primary concerns are cardiac contraindications (bradycardia, LVD, concomitant beta-blocker use in heart failure) rather than renal impairment. Standard monitoring of renal function is recommended during chronic use as with any long-term medication, but this does not constitute a contraindication. 1, 2