Lisinopril and Cyclothiazide: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclothiazide
No brand names on recordLisinopril
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.
Both of these medicines lower your blood pressure, just in different ways. Cyclothiazide is a water pill (diuretic) that makes you lose extra fluid and salt. Lisinopril relaxes your blood vessels. When you start lisinopril while already taking a water pill, your blood pressure can drop more than expected, especially with the very first doses.
You might feel dizzy or lightheaded, particularly when standing up quickly. The good news is that this effect is usually short-lived, and your care team knows how to handle it by adjusting your dose or how you start. If you feel faint, sit or lie down and let your doctor or pharmacist know.
Effect: Additive antihypertensive effect with risk of first-dose hypotension, including severe postural hypotension, when an ACE inhibitor (lisinopril) is initiated in a patient already on thiazide diuretic (cyclothiazide) therapy.
Mechanism: Vasodilation plus relative intravascular volume/sodium depletion from the diuretic. This is a pharmacodynamic (not PK) interaction. Neither drug is a prodrug.
- Onset: rapid (first-dose phenomenon)
- Evidence: theoretical, but well-recognized clinically
- Management: Consider reducing/holding the diuretic or liberalizing sodium before ACE-I initiation; if not feasible, use a reduced lisinopril starting dose. Monitor BP and orthostatic symptoms, especially in volume-depleted patients. Effect is usually transient.
What happens
Reduction of blood pressure
Interaction Deep Dive
When an ACE inhibitor is started in patients already receiving diuretics, blood pressure may fall to an excessive degree3. Cases of severe postural hypotension have been documented following the addition of an ACE inhibitor to diuretic treatment. This effect has appeared more frequently with loop diuretics; however, first dose hypotension occurs commonly among patients who are sodium depleted or hypovolemic as a result of diuretic use or restricted sodium intake. Typically, this drop in blood pressure is transient6271. To reduce the likelihood of hypotensive effects, the diuretic can be lowered or stopped, or salt intake can be raised, prior to beginning ACE inhibitor therapy. Should these approaches not be feasible, the initial ACE inhibitor dose should be reduced3.
Why it happens (mechanism)
Vasodilation and relative intravascular volume depletion
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This is a manageable combination that many people use safely together.
Your care team may take steps to prevent your blood pressure from dropping too much, such as:
- Lowering or briefly pausing the water pill before starting lisinopril
- Adjusting your salt intake if appropriate
- Starting lisinopril at a lower dose and monitoring you more closely
Tell your pharmacist or doctor if you feel dizzy, lightheaded, or faint, especially when standing up. Rising slowly from sitting or lying down can help while your body adjusts.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a randomized crossover trial (N=19), the simultaneous use of hydrochlorothiazide and enalapril in older patients (62 to 84 years) demonstrated that enalapril pharmacokinetics were relatively unaffected by hydrochlorothiazide, however there was a significant rise in AUC (0 to 24 hours) and a significant decrease in the renal clearance of enalaprilat 4.
b) A slight decrease in peak serum concentrations of perindoprilat, along with a reduction in the proportion of the perindopril dose excreted as perindoprilat in the urine, has been reported when perindopril and hydrochlorothiazide are given together 5.
Common questions
Can I take Lisinopril and Cyclothiazide together?
Starting lisinopril while on the water pill cyclothiazide can cause a bigger-than-expected drop in blood pressure at first, so watch for dizziness and let your care team adjust your dose or monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Cyclothiazide 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 is the Lisinopril and Cyclothiazide interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This is a manageable combination that many people use safely together. Your care team may take steps to prevent your blood pressure from dropping too much, such as: Lowering or briefly pausing the water pill before starting lisinopril Adjusting your salt intake if appropriate Starting lisinopril at a lower dose an… Management is individual — always follow your own care team's guidance.
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 Lisinopril or Cyclothiazide 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)
- 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
- 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
- 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
- Todd PA & Fitton A: Perindopril: a review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs 1991; 42:90-114.
- 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 Cyclothiazide
Keep reading about Lisinopril
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist