Adding Amlodipine 5mg Daily for Uncontrolled Hypertension
Yes, add amlodipine 5mg once daily as the next step for uncontrolled hypertension, particularly if the patient is already on an ACE inhibitor or ARB, as this combination provides complementary mechanisms of blood pressure control through both vasodilation and renin-angiotensin system blockade. 1
Rationale for Adding Amlodipine
The combination of an ACE inhibitor or ARB with amlodipine represents guideline-recommended dual therapy that has demonstrated superior blood pressure control compared to either agent alone. 1, 2
Amlodipine provides 24-hour blood pressure control with once-daily dosing, maintaining effective blood levels throughout the dosing interval without altering the normal circadian pattern. 3, 4
For patients already on a thiazide diuretic, adding amlodipine creates the evidence-based triple therapy combination (ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic) that targets different mechanisms: volume reduction, vasodilation, and renin-angiotensin system blockade. 1, 5
Dosing and Titration Strategy
Start with amlodipine 5mg once daily, which is the recommended initial antihypertensive dose for most patients. 6
Small, fragile, or elderly patients may be started on 2.5mg once daily, with cautious titration to the target dose. 7, 6
Wait 7 to 14 days between titration steps, though more rapid titration is acceptable if clinically warranted with frequent patient assessment. 6
The maximum dose is 10mg once daily if blood pressure remains uncontrolled after 6 weeks at 5mg daily. 6, 8
Do not increase the dose before 6 weeks of treatment at 5mg once daily, as there is no advantage in early dose escalation in terms of antihypertensive effect. 8
Expected Outcomes and Monitoring
Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg for higher-risk patients. 1, 5
Reassess blood pressure within 2-4 weeks after starting amlodipine, with the goal of achieving target blood pressure within 3 months of initiating therapy. 1, 5
The combination of amlodipine with an ACE inhibitor produces important additional antihypertensive effects, with responder rates of 87% compared to 67.5% with amlodipine alone. 3, 2
Monitor for peripheral edema, which occurs less frequently when amlodipine is combined with an ACE inhibitor or ARB compared to amlodipine monotherapy. 1, 2
When to Add a Third Agent
If blood pressure remains uncontrolled after optimizing amlodipine to 10mg daily, add a thiazide or thiazide-like diuretic (chlorthalidone 12.5-25mg or hydrochlorothiazide 25mg daily) as the third agent. 1, 5
Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action and proven cardiovascular disease reduction in trials. 1
Check serum potassium and creatinine 2-4 weeks after initiating diuretic therapy to detect potential hypokalemia or changes in renal function. 1
Special Population Considerations
For Black patients specifically, the combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus an ACE inhibitor/ARB. 1
For patients with chronic kidney disease, heart failure, or coronary artery disease, the combination of amlodipine with an ACE inhibitor or ARB is particularly beneficial. 1
In patients with hepatic insufficiency, start with 2.5mg once daily and titrate cautiously. 6
Critical Pitfalls to Avoid
Do not combine an ACE inhibitor with an ARB when adding amlodipine, as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1, 5
Do not use non-dihydropyridine calcium channel blockers (diltiazem or verapamil) if the patient has left ventricular dysfunction or heart failure. 1
Limiting factors for dose increase are usually systemic hypotension and lower limb peripheral edema—monitor closely for these side effects. 7
Confirm medication adherence and rule out secondary causes of hypertension before assuming treatment failure. 1, 9