Can I add lisinopril (Angiotensin-Converting Enzyme inhibitor) to a patient's regimen already taking amlodipine (Calcium Channel Blocker)?

Can You Add Lisinopril to Amlodipine?

Yes, you can and should add lisinopril to amlodipine—this is a highly effective, guideline-recommended combination for blood pressure control that works through complementary mechanisms and is superior to either agent alone. 1

Rationale for This Combination

The combination of an ACE inhibitor (lisinopril) with a calcium channel blocker (amlodipine) is one of the preferred two-drug regimens across multiple international guidelines 1. This pairing works synergistically because:

• Amlodipine causes vasodilation through calcium channel blockade, which can trigger compensatory activation of the renin-angiotensin system 2
• Lisinopril blocks this compensatory mechanism, preventing the body from counteracting amlodipine's blood pressure-lowering effect 2
• The combination produces significantly greater blood pressure reduction than either drug alone at comparable doses 2, 3

Evidence Supporting This Combination

The 2017 ACC/AHA guidelines explicitly recommend ACE inhibitors or ARBs combined with CCBs as a preferred two-drug combination for achieving blood pressure targets below 130/80 mmHg 1. The 2014 international hypertension guidelines review confirms this is one of the most effective pairings, with consensus forming across guideline societies 1.

Research demonstrates the clinical superiority of this combination:

• In patients with essential hypertension, the combination of amlodipine 2.5 mg plus lisinopril 5 mg achieved target blood pressure in a higher percentage of patients than higher doses of either drug alone (amlodipine 5 mg achieved 71% control, lisinopril 10 mg achieved 72% control as monotherapy) 2
• Both drugs together produce additive blood pressure lowering without significantly increasing adverse effects 2, 3
• The combination is well-tolerated, with side effects remaining mild to moderate 3

Practical Dosing Strategy

Start with standard initial doses and titrate based on response:

• Begin with amlodipine 5 mg plus lisinopril 10 mg once daily if the patient is already on amlodipine monotherapy 2, 3
• Lower initial doses (amlodipine 2.5 mg plus lisinopril 5 mg) can be highly effective and may be preferred to minimize side effects while still achieving superior blood pressure control compared to higher monotherapy doses 2
• Titrate upward if needed to amlodipine 10 mg plus lisinopril 20 mg for maximum effect 3
• Review and adjust every 2-4 weeks until blood pressure is controlled 1

When Three Drugs Are Needed

If the amlodipine-lisinopril combination fails to achieve target blood pressure:

• Add a thiazide diuretic as the third agent—this is the preferred triple therapy recommended by multiple guidelines 1, 4
• A diuretic is more effective than a beta-blocker when added to amlodipine plus lisinopril for patients not achieving control 5
• Specifically, bendrofluazide 5 mg once daily produces significantly greater blood pressure reduction than atenolol 100 mg when added to this combination 5

Important Caveats and Monitoring

Monitor renal function and potassium levels within 1-2 weeks after adding lisinopril, especially in patients with pre-existing kidney disease, diabetes, elderly patients, or those on NSAIDs 4. The combination of ACE inhibitors with certain medications requires vigilance:

• NSAIDs like naproxen can reduce the effectiveness of lisinopril and increase risk of acute kidney injury 4
• Check blood pressure closely after initiating the combination to ensure adequate control 4
• Watch for hyperkalemia, particularly in high-risk patients 4

Special Population Considerations

In Black patients with hypertension, thiazide diuretics or CCBs are more effective than ACE inhibitors as monotherapy 1. However, the combination of amlodipine plus lisinopril produces similar blood pressure lowering in Black patients as in other racial groups 1. Therefore, this combination remains appropriate and effective across all racial and ethnic groups 1.

In patients with diabetes, ACE inhibitors provide additional renoprotective benefits beyond blood pressure control 1. The combination of amlodipine and lisinopril is particularly rational in diabetic patients with hypertension 1.

What NOT to Do

Never combine lisinopril with an ARB—this dual RAAS blockade increases risk of end-stage renal disease and stroke without additional benefit 1.