Hydrochlorothiazide and Perindopril: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Hydrochlorothiazide
Perindopril
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduction of blood pressure
Interaction Deep Dive
In patients on diuretic therapy, initiation of ACE inhibitor therapy may cause excessive reduction of blood pressure4. Severe postural hypotension has been reported when ACE inhibitors are added to diuretic therapy. Although this problem has been more commonly observed with loop diuretics, first dose hypotension is common in patients with sodium depletion or hypovolemia due to diuretics or sodium restriction. This hypotensive response is usually transient 6273. Before starting ACE inhibitor therapy, decreasing or discontinuing the diuretic or increasing salt intake may minimize the risk of hypotensive effects. If these measures are not possible, reduce the ACE inhibitor starting dose 4.
Why it happens (mechanism)
Vasodilation and relative intravascular volume depletion
Literature reports
2 reports — tap to read
a) In a randomized crossover study (N=19), concomitant hydrochlorothiazide and enalapril administration in older patients (62 to 84 years) showed that the pharmacokinetics of enalapril were relatively unaffected by hydrochlorothiazide, but a there was a significant increase in AUC (0 to 24 hours) and a significant reduction in renal clearance of enalaprilat 5.
b) A minor reduction in peak serum levels of perindoprilat, and a decrease in the fraction of the perindopril dose excreted as perindoprilat in the urine, has been reported with concomitant administration of perindopril and hydrochlorothiazide 1.
Common questions
Can I take Hydrochlorothiazide and Perindopril together?
Reduction of blood pressure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Hydrochlorothiazide and Perindopril interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Hydrochlorothiazide or Perindopril need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (7)
- Todd PA & Fitton A: Perindopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs 1991; 42:90-114.
- Gluck Z, Beretta-Piccoli C, & Reubi FC: Long-term effects of captopril on renal function in hypertensive patients. Eur J Clin Pharmacol 1984; 26:315-323. PubMed
- Vlasses PH, Ferguson RK, & Chatterjee K: Captopril: clinical pharmacology and benefit-to-risk ratio in hypertension and congestive heart failure. Pharmacotherapy 1982; 2:1-17. PubMed
- Product Information: QBRELIS(TM) oral solution, lisinopril oral solution. Silvergate Pharmaceuticals (per manufacturer), Greenwood Village, CO, 2016. DailyMed
- Weisser K, Schloos J, Jakob S, et al: The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients. Eur J Clin Pharmacol 1992; 43:173-177. PubMed
- Atkinson AB, Brown JJ, Morton JJ, et al: Captopril in a hyponatremic hypertensive; need for caution initiating therapy (letter). Lancet 1979; 1:557-558.
- Pandhi P, Mondal S, Sharma BK, et al: Low dose captopril alone and in combination with hydrochlorothiazide in treatment of mild to moderate essential hypertension. Int J Clin Pharmacol Ther Toxicol 1986; 24:294-297.
Keep reading about Hydrochlorothiazide
Keep reading about Perindopril
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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