What are the potential interactions and management considerations for Perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor) in patients with hypertension?

From the Guidelines

Perindopril requires careful monitoring for several important drug interactions and patient-specific considerations, particularly in patients with hypertension, and should be used with caution in combination with other antihypertensives, diuretics, potassium-sparing agents, and NSAIDs due to the increased risk of hyperkalemia and hypotension 1. When initiating perindopril therapy, it is essential to consider the potential interactions with other medications, such as:

• Potassium-sparing diuretics, potassium supplements, and NSAIDs, which can increase the risk of hyperkalemia
• Lithium, which may have elevated levels when used with perindopril, potentially causing lithium toxicity
• Other antihypertensives or diuretics, which can increase the risk of hypotension, particularly with the first dose Management considerations for perindopril therapy include:
• Starting at a lower dose (2-4 mg daily) in elderly patients, those with renal impairment (eGFR <60 ml/min), or patients on diuretics
• Regular monitoring of blood pressure, renal function, and serum potassium, especially during the first few weeks of treatment
• Avoiding use in pregnancy (particularly second and third trimesters) due to fetal risks, in patients with a history of angioedema related to previous ACE inhibitor therapy, and in those with bilateral renal artery stenosis
• Advising patients about the risk of first-dose hypotension and the importance of reporting symptoms like persistent dry cough, dizziness, or swelling of the face, lips, or tongue immediately 1. The European Society of Hypertension and the European Society of Cardiology recommend ACE inhibitors, such as perindopril, as a preferred treatment option for patients with hypertension, particularly those with subclinical organ damage, left ventricular hypertrophy, or diabetes mellitus 1.

From the FDA Drug Label

Formal interaction studies of perindopril erbumine tablets have not been carried out with antihypertensive agents other than thiazides. Limited experience in controlled and uncontrolled trials coadministering perindopril erbumine tablets with a calcium channel blocker, a loop diuretic or triple therapy (beta-blocker, vasodilator and a diuretic), does not suggest any unexpected interactions In general, ACE inhibitors have less than additive effects when given with beta-adrenergic blockers, presumably because both work in part through the renin angiotensin system. A controlled pharmacokinetic study has shown no effect on plasma digoxin concentrations when coadministered with perindopril erbumine tablets.

The potential interactions and management considerations for Perindopril in patients with hypertension include:

• Limited interaction data: Formal interaction studies with antihypertensive agents other than thiazides are lacking 2.
• No unexpected interactions: Coadministration with calcium channel blockers, loop diuretics, or triple therapy did not suggest unexpected interactions 2.
• Less than additive effects with beta-blockers: ACE inhibitors like perindopril may have less than additive effects when given with beta-adrenergic blockers 2.
• No effect on digoxin concentrations: Coadministration with perindopril did not affect plasma digoxin concentrations 2.

From the Research

Potential Interactions with Perindopril

• Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, may interact with other medications, including thiazide diuretics, which can enhance its hypotensive effects 3, 4.
• Combination treatment with perindopril and an antihypertensive agent from another treatment class can provide additional benefits, either as first-line treatment or in patients failing to respond to monotherapy 5.
• Perindopril may also interact with trimethoprim, a potassium-sparing diuretic, which can increase the risk of hyperkalemia in high-risk patients 6.

Management Considerations

• Patients with hypertension should be monitored regularly for changes in blood pressure, renal function, and electrolyte levels while taking perindopril 3, 5.
• Dose adjustments may be necessary when perindopril is combined with other medications, such as thiazide diuretics or trimethoprim 4, 6.
• Perindopril has a similar adverse event profile to that of other ACE inhibitors, with cough being the most common event reported during treatment 5.
• The cardioprotective benefits of perindopril, including anti-atherosclerotic, anti-inflammatory, and antithrombotic properties, can extend to all patients with vascular disease, regardless of blood pressure level 7.