What is the recommended dosing for perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

Perindopril Dosing Recommendations

Stable Coronary Artery Disease

For patients with stable coronary artery disease, initiate perindopril at 4 mg once daily for 2 weeks, then increase to the target maintenance dose of 8 mg once daily if tolerated. 1

• In elderly patients (>70 years), use a more gradual titration: start with 2 mg once daily for the first week, increase to 4 mg once daily in the second week, then advance to 8 mg once daily for maintenance if tolerated 1
• The EUROPA trial demonstrated cardiovascular benefit with perindopril 8 mg daily in patients with documented coronary artery disease 2

Essential Hypertension

For uncomplicated hypertension, start perindopril at 4 mg once daily and titrate upward to a maximum of 16 mg per day based on blood pressure control measured just before the next dose. 1

• The usual maintenance dose range is 4 to 8 mg administered as a single daily dose 1
• Perindopril may be administered in two divided doses if needed, though once-daily dosing is generally preferred 1
• In elderly patients (>65 years), the recommended initial dose is 4 mg daily given in one or two divided doses, with titration as tolerated 1
• Exercise caution with doses exceeding 8 mg in elderly patients due to limited clinical experience; doses above 8 mg should be administered under close medical supervision 1

Combination with Diuretics

If blood pressure is inadequately controlled with perindopril alone, add a diuretic rather than exceeding recommended perindopril doses. 1

• In patients currently on diuretic therapy, discontinue the diuretic 2 to 3 days before initiating perindopril if possible to reduce the risk of symptomatic hypotension 1
• If the diuretic cannot be discontinued, use an initial perindopril dose of 2 to 4 mg daily (in one or two divided doses) with careful medical supervision for several hours until blood pressure stabilizes 1
• Monitor patients closely for the first two weeks of treatment and whenever doses of perindopril and/or diuretics are increased 1

Stroke Prevention and Diabetes

In patients with prior stroke or TIA, perindopril 4 mg daily combined with indapamide 2.5 mg daily is effective for secondary prevention. 2

• The PROGRESS trial used this combination in patients with stroke or TIA within the previous 5 years 2
• For patients with type 2 diabetes and cardiovascular risk factors, the ADVANCE trial demonstrated benefit with perindopril 2 mg daily plus indapamide 0.625 mg initially, increased after 3 months to perindopril 4 mg daily plus indapamide 1.25 mg daily 2

Renal Impairment Adjustments

In patients with creatinine clearance below 30 mL/min, perindopril safety and efficacy have not been established and should be avoided. 1

• For creatinine clearance above 30 mL/min, start with 2 mg daily and do not exceed 8 mg daily due to limited clinical experience 1
• Perindoprilat (the active metabolite) accumulates significantly in renal impairment, with accumulation ratios of 1.81 in mild renal failure and 5.35 in severe renal failure 3
• During dialysis, perindopril is removed with the same clearance as in patients with normal renal function 1

Important Clinical Considerations

• Maximal ACE inhibition occurs 4 to 6 hours after dosing, with substantial effects persisting at 24 hours 4, 5, 6
• Perindopril is a prodrug requiring conversion to perindoprilat for ACE inhibition, with peak perindoprilat concentrations reached 2 to 6 hours after oral administration 5, 6
• Monitor renal function and electrolytes within 1-2 weeks after initiating therapy or changing doses 7
• Avoid routine combination of ACE inhibitors with ARBs and aldosterone antagonists due to increased risk of hyperkalemia and renal dysfunction 2