Can you give amlodipine and Cardizem (diltiazem) together?

Amlodipine and Diltiazem Combination Therapy: Safety Concerns and Recommendations

The concurrent use of amlodipine and diltiazem (Cardizem) is generally not recommended due to the increased risk of additive hypotension, bradycardia, and conduction disturbances that could lead to significant cardiovascular complications. 1

Pharmacological Rationale for Avoiding Combination

Amlodipine and diltiazem work through different mechanisms and have distinct effects on the cardiovascular system:

• Amlodipine: A dihydropyridine calcium channel blocker (CCB) that primarily affects peripheral vasculature with minimal cardiac effects 1
• Diltiazem: A non-dihydropyridine CCB that significantly affects cardiac conduction and contractility 1

When combined, these medications can cause:

1. Additive hypotension: Both medications lower blood pressure through different mechanisms
2. Excessive bradycardia: Diltiazem has significant effects on heart rate that can be exacerbated when combined with amlodipine 2
3. Conduction abnormalities: Risk of AV block or sinus node dysfunction 3

Pharmacokinetic Interactions

Diltiazem is a moderate inhibitor of CYP3A4, which can affect the metabolism of amlodipine (a CYP3A4 substrate):

• Co-administration of diltiazem with amlodipine resulted in a 60% increase in amlodipine systemic exposure in elderly hypertensive patients 4
• This interaction increases the risk of adverse effects from amlodipine

High-Risk Patient Groups

The combination should be particularly avoided in patients with:

• Pre-existing bradycardia
• AV block (any degree)
• Sick sinus syndrome
• Heart failure with reduced ejection fraction (HFrEF)
• Hypotension
• Renal or hepatic impairment
• Elderly patients 1, 3

Alternative Therapeutic Approaches

If additional antihypertensive therapy is needed beyond a single CCB, consider:

1. Different drug class combinations: Add an ACE inhibitor, ARB, or thiazide diuretic instead of a second CCB 1
2. Single CCB selection based on indication:
   • For vasospastic angina: Amlodipine (5-10mg daily)
   • For rate control plus hypertension: Diltiazem (120-360mg daily) 1

Monitoring Requirements If Combination Is Unavoidable

In rare situations where the combination cannot be avoided:

• Obtain baseline ECG before initiating combination therapy
• Monitor blood pressure and heart rate frequently
• Start with the lowest possible doses of both medications
• Regularly assess for conduction abnormalities
• Consider inpatient monitoring when initiating therapy in high-risk patients 3, 2

Documented Adverse Events

Several studies have reported serious adverse events with this combination:

• Cases of profound sinus bradycardia requiring hospitalization 2
• Increased risk of conduction disturbances even in patients with uncomplicated hypertension 3
• Potential for sinus arrest in susceptible individuals 2

While some older studies have explored using different types of calcium channel blockers together for resistant hypertension 5, modern guidelines and more recent evidence do not support this practice due to safety concerns.

Conclusion

The combination of amlodipine and diltiazem should generally be avoided due to the increased risk of serious cardiovascular adverse effects. Alternative therapeutic strategies using different antihypertensive drug classes are preferred for patients requiring combination therapy.