What is the maximum recommended dose of perindopril (angiotensin-converting enzyme inhibitor) for treating hypertension?

Maximum Dose of Perindopril for Hypertension

The maximum recommended dose of perindopril for treating hypertension is 16 mg once daily, though the usual maintenance dose range is 4 to 8 mg administered as a single daily dose. 1

Dosing Guidelines for Perindopril

Initial Dosing

• Standard initial dose: 4 mg once daily
• Elderly patients (>65 years): 4 mg once daily
• Very elderly patients (>70 years): 2 mg once daily for the first week

Dose Titration

• Dosage may be titrated upward until blood pressure is controlled
• Titration typically occurs in 2-4 week intervals
• Can be administered as a single daily dose or in two divided doses
• When comparing once-daily to twice-daily dosing, the twice-daily regimen was slightly superior, but only by about 0.5 to 1.0 mmHg 1

Maximum Dosing

• Maximum dose: 16 mg per day 1
• Usual maintenance dose range: 4 to 8 mg daily 1
• Elderly patients: Doses exceeding 8 mg should be administered with caution and under close medical supervision 1

Special Populations and Considerations

Elderly Patients

• Initial dose for patients >65 years: 4 mg daily (one or two divided doses)
• Initial dose for patients >70 years: 2 mg once daily in the first week, followed by 4 mg once daily in the second week 1
• Doses above 8 mg require caution and close monitoring in elderly patients 1

Renal Impairment

• Perindoprilat elimination is decreased in renally impaired patients
• Marked increase in accumulation when creatinine clearance drops below 30 mL/min
• Safety and efficacy not established in patients with creatinine clearance <30 mL/min 1

Concomitant Diuretic Use

• If a patient is currently on a diuretic:
  • If possible, discontinue diuretic 2-3 days before starting perindopril
  • If diuretic cannot be discontinued, start with lower perindopril dose (2-4 mg daily)
  • Close medical supervision required for several hours after first dose 1

Clinical Efficacy and Dose Requirements

• Studies show that perindopril 4 to 8 mg once daily is usually effective for blood pressure control in patients with mild to moderate essential hypertension 2
• Higher doses (8 mg) may be required for patients with multiple cardiovascular risk factors 3
• The PEACH study demonstrated that patients with more cardiovascular risk factors were more likely to require high-dose perindopril (8 mg) for blood pressure control 3

Pharmacodynamics and Duration of Action

• Perindopril is a prodrug that is hydrolyzed to the active metabolite, perindoprilat
• Once-daily administration provides adequate 24-hour inhibition of ACE 2
• Maximal ACE inhibition occurs 4-6 hours after oral dosing with substantial inhibition persisting beyond 24 hours 4
• Trough/peak ratios of >50% indicate good 24-hour blood pressure control 5

Common Pitfalls and Caveats

• Monitor renal function and potassium levels, particularly when initiating therapy
• Dry cough is the most common adverse event and most common reason for treatment withdrawal 5
• Symptomatic hypotension can occur after initial dose, especially in patients on diuretics
• Contraindicated in patients with history of angioedema related to previous ACE inhibitor therapy
• Use with caution in patients with renal artery stenosis

Perindopril has demonstrated efficacy in reducing cardiovascular events in various populations, including those with stable coronary artery disease and diabetes, making it a valuable option in the management of hypertension, particularly for patients with additional cardiovascular risk factors.