In a patient with hypertension uncontrolled on a renin‑angiotensin system blocker, beta‑blocker, or thiazide diuretic, when should amlodipine 5 mg be added as augmentation therapy?

Augmenting Hypertension Therapy with Amlodipine 5 mg

When to Add Amlodipine as Second-Line Therapy

Add amlodipine 5 mg once daily when blood pressure remains ≥140/90 mmHg despite optimal monotherapy with a renin-angiotensin system blocker, beta-blocker, or thiazide diuretic. 1

Rationale for Adding Amlodipine

• Amlodipine provides complementary vasodilation through calcium-channel blockade when combined with RAS blockers, beta-blockers, or diuretics, targeting different mechanisms to achieve superior blood pressure control compared to dose escalation of a single agent. 1, 2
• The combination of amlodipine with an ACE inhibitor or ARB is particularly beneficial for patients with chronic kidney disease, heart failure, or coronary artery disease, and may attenuate amlodipine-related peripheral edema. 1
• Adding amlodipine to a thiazide diuretic is especially effective for volume-dependent hypertension, elderly patients, or Black patients. 1

Dosing Strategy

• Start with amlodipine 5 mg once daily and reassess blood pressure after 2–4 weeks before considering dose escalation to 10 mg. 1, 3
• Do not increase the dose to 10 mg until after at least 4–6 weeks at 5 mg, as blood pressure reduction continues steadily through the sixth week of treatment, and early dose escalation provides no additional benefit. 3
• Amlodipine's long half-life (35–50 hours) ensures sustained 24-hour blood pressure control even if a dose is occasionally missed, providing continuous protection against incidental non-compliance. 4, 5

Blood Pressure Targets and Monitoring

• Target blood pressure is <130/80 mmHg for most patients, with a minimum acceptable goal of <140/90 mmHg. 1
• Re-measure blood pressure 2–4 weeks after adding amlodipine, with the goal of achieving target blood pressure within 3 months of therapy modification. 1
• Amlodipine maintains smooth 24-hour blood pressure control without orthostatic hypotension or alteration of the normal circadian pattern. 6, 5

Special Population Considerations

• For Black patients: The combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus an ACE inhibitor/ARB due to lower renin activity in this population. 1
• For elderly patients: Amlodipine is particularly appropriate because it controls blood pressure effectively, protects against stroke and myocardial infarction, and does not cause orthostatic hypotension. 4, 6
• For patients with diabetes or chronic kidney disease: Amlodipine controls blood pressure without worsening glycemic control or kidney function. 4

Escalation to Triple Therapy

• If blood pressure remains ≥140/90 mmHg after optimizing amlodipine to 10 mg daily, add a third agent from the remaining class (RAS blocker, diuretic, or calcium-channel blocker) to achieve guideline-recommended triple therapy. 1
• The preferred triple regimen is RAS blocker + calcium-channel blocker + thiazide diuretic, which targets complementary mechanisms: renin-angiotensin blockade, vasodilation, and volume reduction. 1

Monitoring for Adverse Effects

• Monitor for peripheral edema, which occurs more commonly at the 10 mg dose; this side effect may be attenuated when amlodipine is combined with an ACE inhibitor or ARB. 1, 4
• Other potential side effects include palpitations, dizziness, and flushing, which are dose-dependent and more frequent at 10 mg. 4
• When combining amlodipine with a thiazide diuretic, check serum potassium and creatinine 2–4 weeks after initiation to detect hypokalemia or renal function changes. 1

Critical Pitfalls to Avoid

• Do not combine an ACE inhibitor with an ARB when adding amlodipine to existing therapy, as dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1
• Do not add a beta-blocker as a third agent unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, atrial fibrillation), as beta-blockers are less effective than calcium-channel blockers or diuretics for stroke prevention. 1
• Do not delay treatment intensification when blood pressure remains uncontrolled; prompt action within 2–4 weeks is required to reduce cardiovascular risk. 1
• Verify medication adherence before adding amlodipine, as non-adherence is the most common cause of apparent treatment resistance. 1

Confirming True Hypertension

• Before adding amlodipine, confirm elevated readings with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) to exclude white-coat hypertension. 1