What is the typical dosing for perindopril (ACE inhibitor) and indapamide (thiazide-like diuretic) in hypertension management?

Perindopril/Indapamide Dosing for Hypertension

The standard dosing regimen is perindopril 2 mg/indapamide 0.625 mg once daily as initial therapy, with titration after 3 months to perindopril 4 mg/indapamide 1.25 mg once daily if blood pressure remains uncontrolled, up to a maximum dose of perindopril 8 mg/indapamide 2.5 mg once daily. 1

Initial Dosing Strategy

• Start with perindopril 2 mg/indapamide 0.625 mg once daily for most patients with uncomplicated hypertension as first-line therapy 1, 2
• This low-dose combination provides effective blood pressure reduction while minimizing adverse effects, particularly hypokalaemia 3
• For patients with blood pressure ≥160/100 mmHg, consider starting directly with the higher dose of perindopril 8 mg/indapamide 2.5 mg once daily for more aggressive initial control 2

Titration Protocol

• After 3 months on the initial dose, if blood pressure targets are not achieved, increase to perindopril 4 mg/indapamide 1.25 mg once daily 1, 4
• The maximum recommended dose is perindopril 8 mg/indapamide 2.5 mg once daily 2, 5
• Check blood pressure 2-4 weeks after any dose adjustment 2

Blood Pressure Targets

• Target blood pressure is <130/80 mmHg for patients with diabetes and hypertension 1
• For most adults without diabetes, aim for systolic BP of 120-129 mmHg if tolerated 6
• Treatment should be individualized, but do not aim for <120/80 mmHg as this is associated with increased adverse events 1

Special Populations

Elderly Patients (>70 years)

• When using perindopril monotherapy in elderly patients, start at 2 mg once daily for 1 week, then 4 mg once daily for 1 week, then 8 mg once daily if tolerated 5
• The perindopril/indapamide combination at 2 mg/0.625 mg once daily is effective and well-tolerated in elderly patients aged 65-85 years 7, 3

Patients with Renal Impairment

• The low-dose combination (perindopril 2 mg/indapamide 0.625 mg) can be used in patients with reduced renal function 8
• Monitor serum creatinine, eGFR, and potassium at least annually, more frequently if risk factors for renal impairment exist 2

Patients with Albuminuria

• Perindopril/indapamide is particularly beneficial for patients with urine albumin-to-creatinine ratio ≥30 mg/g due to renoprotective effects of ACE inhibitors 2

When Combination Therapy Fails

If blood pressure remains elevated on maximum dose perindopril/indapamide:

• Add a dihydropyridine calcium channel blocker (amlodipine 5-10 mg daily) to create the preferred three-drug combination of ACE inhibitor + thiazide-like diuretic + CCB 6
• Do not combine with another ACE inhibitor, ARB, or direct renin inhibitor due to increased risk of hyperkalemia, syncope, and acute kidney injury without added cardiovascular benefit 2
• Reassess blood pressure within 2-4 weeks after adding the third agent 6

Monitoring Requirements

• Check blood pressure at every routine visit or at least every 6 months 1
• Monitor serum potassium, sodium, and renal function, particularly with doses above 2.5 mg indapamide 9
• Check renal function and electrolytes 1-2 weeks after initiation in patients with risk factors for renal impairment 6

Important Clinical Considerations

Concomitant Diuretic Use

• If patient is already on a diuretic, discontinue it 2-3 days before starting perindopril if possible to reduce risk of symptomatic hypotension 5
• If diuretic cannot be discontinued, start with perindopril 2-4 mg daily with careful monitoring for several hours until blood pressure stabilizes 5

Evidence Base

The ADVANCE trial demonstrated that the fixed combination of perindopril 4 mg/indapamide 2.5 mg (starting at 2 mg/0.625 mg and titrating after 3 months) significantly reduced cardiovascular death, nonfatal stroke/MI, and microvascular complications in patients with type 2 diabetes 1. The achieved systolic blood pressure was 135 mmHg in the treatment group versus 140 mmHg in placebo 1.

Common Pitfalls

• The most common adverse events are headache and cough 7
• Hypokalaemia occurs more frequently with this combination than with monotherapy, though less than with indapamide alone 7, 3
• Monitor closely for hypotension after the first dose, especially in elderly patients or those on concurrent diuretics 5