Can captopril (angiotensin-converting enzyme inhibitor) and amlodipine (calcium channel blocker) be given together?

Captopril and Amlodipine Combination Therapy for Hypertension

Yes, captopril (an angiotensin-converting enzyme inhibitor) and amlodipine (a calcium channel blocker) can be safely and effectively given together as combination therapy for hypertension. This combination provides complementary mechanisms of action that can lead to enhanced blood pressure control in patients with resistant hypertension.

Evidence Supporting Combination Therapy

• The combination of calcium antagonists (like amlodipine) and ACE inhibitors (like captopril) is recognized as an effective and well-tolerated two-drug combination for hypertension management 1
• Clinical studies specifically examining captopril and amlodipine combinations have demonstrated significant additional blood pressure-lowering effects compared to monotherapy with either agent 2, 3
• In patients with moderate-to-severe hypertension uncontrolled on low-dose captopril alone, adding amlodipine 10mg daily produced significant additional reductions in both systolic and diastolic blood pressure (placebo-corrected differences of -18/-12 mmHg for supine and -20/-12 mmHg for standing measurements) 3

Pharmacological Rationale

• ACE inhibitors like captopril and calcium channel blockers like amlodipine have different and complementary mechanisms of action, making their combination particularly effective 1
• Captopril blocks the renin-angiotensin-aldosterone system, while amlodipine blocks calcium channels in vascular smooth muscle, providing dual pathways for blood pressure reduction 1
• This combination is especially useful when monotherapy with either agent fails to achieve adequate blood pressure control 2, 3

Safety Considerations

• The combination of captopril and amlodipine is generally well-tolerated, with clinical studies showing no patients discontinuing therapy due to adverse effects 2, 3
• Common side effects when combining these medications include ankle edema and flushing 3
• No significant treatment-related effects on biochemical and hematologic parameters have been noted with this combination 2

Clinical Applications

• This combination is particularly useful for patients with resistant hypertension not controlled on monotherapy 2, 3
• The European Society of Hypertension and European Society of Cardiology specifically list calcium antagonist and ACE inhibitor combinations among their preferred two-drug combinations for hypertension management 1
• For patients requiring multiple antihypertensive agents, this combination provides 24-hour blood pressure control with once-daily amlodipine and twice-daily captopril dosing 4

Dosing Considerations

• Typical dosing in clinical studies involved captopril 25mg twice daily with amlodipine 5-10mg once daily 2, 3
• When initiating combination therapy, starting with lower doses of each agent may help minimize side effects 5
• Amlodipine's long half-life allows for once-daily dosing, which can improve adherence when combined with captopril 5, 4

Potential Advantages Over Other Combinations

• Unlike the combination of ACE inhibitors with ARBs (which is not recommended due to increased adverse events without improved survival), the captopril-amlodipine combination has demonstrated safety and efficacy 1
• Compared to captopril alone, the combination with amlodipine provides more sustained 24-hour blood pressure control 4
• The combination may be particularly beneficial in patients with comorbid conditions like coronary artery disease, where both classes have demonstrated benefits 1

Special Population Considerations

• This combination may be particularly effective in Black patients who might have a reduced response to ACE inhibitor monotherapy 6
• The response to amlodipine tends to be greater in patients with higher initial blood pressure, making the combination especially useful for more severe hypertension 6

Remember that while fixed-dose combinations of various ACE inhibitors and calcium channel blockers exist (including benazepril-amlodipine and trandolapril-verapamil), a specific fixed-dose combination of captopril-amlodipine is not listed among the available combinations in the guidelines 1.