Can you give amlodipine and diltiazem (calcium channel blockers) together?

Concurrent Use of Amlodipine and Diltiazem

Amlodipine and diltiazem should not be used together due to the high risk of severe bradycardia, heart block, and hypotension from their additive effects on cardiac conduction and blood pressure. 1

Pharmacological Considerations

Mechanism of Action and Classification

Both medications are calcium channel blockers (CCBs) but with different properties:

• Amlodipine: Dihydropyridine CCB

  • Primarily causes peripheral vasodilation
  • Minimal effects on cardiac conduction and contractility
  • Metabolized by CYP3A4 2

• Diltiazem: Non-dihydropyridine CCB

  • Moderate vasodilation effects
  • Significant effects on cardiac conduction (AV node, SA node)
  • Negative inotropic and chronotropic effects
  • Inhibits CYP3A4 1

Drug Interaction Mechanism

When used together, these medications create a dangerous interaction:

1. Diltiazem inhibits CYP3A4, which metabolizes amlodipine
2. Co-administration of diltiazem with amlodipine results in a 60% increase in amlodipine systemic exposure 2
3. The combination produces additive effects on blood pressure reduction
4. More concerning is the enhanced negative effect on cardiac conduction 1, 3

Clinical Risks

Cardiovascular Risks

• Profound sinus bradycardia or sinus arrest 3
• AV block
• Severe hypotension
• Worsening heart failure in patients with ventricular dysfunction 1

High-Risk Populations

• Elderly patients
• Patients with renal or hepatic impairment
• Patients with pre-existing conduction abnormalities
• Patients with heart failure or left ventricular dysfunction 4

Evidence from Guidelines

The 2018 expert consensus document from Nature Reviews Cardiology explicitly states:

• "Diltiazem and verapamil should not be used in combination with ivabradine owing to the risk of severe bradycardia." 1
• While this statement specifically mentions ivabradine, the same physiological concern applies to combining two calcium channel blockers with overlapping mechanisms.

The ACC/AHA guidelines note that:

• "Major side effects include hypotension, worsening HF, bradycardia, and AV block." 1
• The guidelines describe the different properties of CCBs but do not recommend combining them.

Alternative Approaches

If enhanced blood pressure control is needed:

1. Optimize single-agent therapy first:

   • Maximize the dose of either amlodipine (up to 10 mg daily) or diltiazem (up to 360 mg daily) 1

2. Consider alternative combinations:

   • Amlodipine + ACE inhibitor or ARB
   • Amlodipine + diuretic
   • Diltiazem + ACE inhibitor or ARB (with caution)

3. If vasospastic angina is the target:

   • Either agent alone is effective; combining them adds risk without proven benefit 1

Conclusion

The combination of amlodipine and diltiazem should be avoided due to the significant risk of severe bradycardia, conduction abnormalities, and hypotension. The pharmacokinetic interaction (diltiazem increasing amlodipine levels) and pharmacodynamic interaction (additive effects on cardiac conduction) create a dangerous clinical scenario with minimal additional therapeutic benefit compared to optimizing therapy with a single agent or using alternative combinations.