What is the recommended dosage and treatment protocol for patients taking Coversyl (Perindopril) for hypertension or heart failure?

Coversyl (Perindopril) Dosing and Treatment Protocol

For hypertension, start perindopril at 4 mg once daily and titrate to a maintenance dose of 4-8 mg daily; for stable coronary artery disease, initiate at 4 mg daily for 2 weeks then increase to 8 mg daily; and for heart failure, begin at 2 mg once daily with gradual up-titration to a target of 4 mg daily. 1

Hypertension Management

Initial Dosing

• Start with 4 mg once daily in uncomplicated hypertensive patients 1
• Titrate upward until blood pressure control is achieved (measured just before next dose) or to a maximum of 16 mg per day 1
• Usual maintenance range is 4-8 mg administered as a single daily dose 1
• Twice-daily dosing may provide slightly superior control (0.5-1.0 mmHg better) compared to once-daily administration 1

Elderly Patients (>65 years)

• Begin with 4 mg daily in one or two divided doses 1
• Titrate upward based on blood pressure response 1
• Exercise caution with doses exceeding 8 mg and provide close medical supervision 1
• For patients >70 years with stable coronary artery disease, use 2 mg daily for week 1, then 4 mg daily for week 2, then 8 mg daily for maintenance 1

Concomitant Diuretic Use

• Discontinue diuretic 2-3 days prior to starting perindopril if possible to reduce risk of symptomatic hypotension 1
• If diuretic cannot be stopped, use initial dose of 2-4 mg daily in one or two divided doses with careful medical supervision for several hours until blood pressure stabilizes 1
• Resume diuretic if blood pressure not controlled with perindopril alone 1
• Monitor closely for first two weeks and whenever doses are adjusted 1

Stable Coronary Artery Disease

Standard Protocol

• Initial dose: 4 mg once daily for 2 weeks 1
• Maintenance dose: 8 mg once daily if tolerated 1
• This regimen demonstrated significant cardiovascular event prevention in the EUROPA trial 2, 3

Elderly Patients (>70 years)

• Week 1: 2 mg once daily 1
• Week 2: 4 mg once daily 1
• Maintenance: 8 mg once daily if tolerated 1

Heart Failure Management

Dosing Strategy

• Starting dose: 2 mg once daily 2
• Target dose: 4 mg once daily 2
• Double the dose at not less than 2-week intervals 2
• Aim for target dose or highest tolerated dose 2

Monitoring Requirements

• Check blood pressure, renal function (urea, creatinine), and potassium 5-7 days after initiation 2
• Recheck every 5-7 days until values are stable 2
• Monitor at 1-2 weeks after each dose increment, at 3 months, then every 6 months 2

Important Precautions

• Always combine with beta-blockers as first-line treatment for NYHA class I-IV heart failure 2
• Consider reducing or withholding diuretics for 24 hours before initiation to minimize hypotension risk 2
• Avoid potassium-sparing diuretics during initiation 2
• Avoid NSAIDs and COX-2 inhibitors 2

Key Contraindications and Cautions

Seek Specialist Advice Before Initiating

• Significant renal dysfunction (creatinine >2.5 mg/dL or >221 μmol/L) 2
• Hyperkalemia (>5.0 mmol/L) 2
• Symptomatic or severe asymptomatic hypotension (systolic BP <90 mmHg) 2

Acceptable Laboratory Changes

• Creatinine increase up to 50% above baseline or to 3 mg/dL (266 μmol/L), whichever is greater 2
• Potassium up to 6.0 mmol/L is acceptable 2

Problem Management

Asymptomatic Hypotension

• Does not require treatment change 2
• If symptomatic, review and reduce non-essential vasodilators (nitrates, calcium channel blockers) 2
• Consider reducing diuretic dose if no signs of congestion 2

Cough

• Common but rarely requires discontinuation (2.8% discontinuation rate) 4
• Exclude pulmonary edema as cause 2
• If proven ACE inhibitor-induced and severely troublesome (disrupting sleep), consider switching to angiotensin receptor blocker 2

Worsening Renal Function

• Stop concomitant nephrotoxic drugs (NSAIDs) 2
• Discontinue non-essential vasodilators 2
• Reduce diuretic dose if no signs of congestion 2
• If excessive rises persist despite these measures, seek specialist advice 2

Clinical Pharmacology

Mechanism and Duration

• Perindopril is a prodrug requiring conversion to perindoprilat for ACE inhibition 5, 6
• Maximal effects occur 4-6 hours after dosing with substantial effects at 24 hours 6
• 70% cleared renally as active metabolite 6
• Provides adequate 24-hour ACE inhibition with once-daily dosing 5

Evidence Base

• Perindopril 4-8 mg once daily demonstrated response rates of 67-80% (DBP ≤90 mmHg), significantly superior to captopril 25-50 mg twice daily (44-57%) 7
• In heart failure, perindopril 4 mg once daily significantly improved exercise tolerance and reduced symptoms over 3 months 4
• Lower incidence of first-dose hypotension with perindopril 2 mg compared to equivalent starting doses of captopril, enalapril, and lisinopril 4