Combining Irbesartan and Perindopril is Dangerous and Should Not Be Done
The simultaneous use of an ACE inhibitor (perindopril), ARB (irbesartan), and/or renin inhibitor is potentially harmful and is not recommended to treat adults with hypertension. 1
Why This Combination is Harmful
Dual RAS Blockade Risks
Dual blockade of the renin-angiotensin system (RAS) with angiotensin receptor blockers and ACE inhibitors is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. 2
Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy, making the risk-benefit ratio unfavorable. 2
Specific Adverse Outcomes
Hyperkalemia risk is substantially elevated, particularly in patients with chronic kidney disease, those on potassium supplements, or those taking potassium-sparing drugs. 1, 2
Acute renal failure risk increases, especially in patients with bilateral renal artery stenosis or volume depletion. 1, 2
Hypotension becomes more likely and potentially severe with dual RAS blockade. 2
Even a Single Dose is Problematic
While the evidence primarily addresses chronic use, even a single exposure initiates the dual RAS blockade mechanism that creates these risks. The concern is not cumulative toxicity but rather the immediate pharmacodynamic interaction:
Both drugs block the same physiological pathway at different points, creating excessive suppression of the renin-angiotensin system. 2
Acute kidney injury can occur rapidly, particularly in volume-depleted patients or those with pre-existing renal compromise. 2
A single dose in a high-risk patient (elderly, dehydrated, pre-existing CKD) could precipitate acute complications. 2
What to Do Instead
If blood pressure is inadequately controlled on either irbesartan or perindopril alone, add a medication from a different class rather than combining two RAS inhibitors:
- Add a calcium channel blocker (amlodipine, felodipine) 1
- Add a thiazide or thiazide-type diuretic (chlorthalidone preferred, or hydrochlorothiazide) 1
- Consider switching to a fixed-dose combination like perindopril/indapamide, which has proven cardiovascular benefit 1
Common Pitfall to Avoid
Do not assume that combining two drugs acting on the same system provides additive benefit—the guidelines explicitly state this combination is harmful, not just ineffective. 1 This is a Class III (Harm) recommendation with Level A evidence, meaning it is contraindicated based on strong clinical trial data. 1