Lisinopril and Buthiazide: 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
Lisinopril
Buthiazide
No brand names on record
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.
Lisinopril is a blood pressure medicine (an ACE inhibitor), and buthiazide is a water pill (a diuretic) that also lowers blood pressure. When you take both, they can work together and drop your blood pressure more than expected, especially with the very first doses of lisinopril.
The main thing to watch for is feeling dizzy, lightheaded, or faint when you stand up quickly. The good news is that this effect is usually temporary, and your care team can manage it easily by adjusting your doses or checking on you more closely at the start. Please don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Additive hypotension, particularly first-dose and postural, when initiating lisinopril in a patient already on the thiazide diuretic buthiazide.
Mechanism: ACE inhibitor vasodilation superimposed on diuretic-induced volume/sodium depletion. Neither agent is a prodrug requiring metabolic activation; this is a pharmacodynamic (not PK) interaction.
- Direction: Enhanced BP lowering (increases_drug_effect on BP).
- Onset: Rapid; typically transient.
- Evidence: Theoretical, but well-recognized class effect.
- Management: Before starting lisinopril, consider reducing/holding the diuretic or liberalizing salt intake; if not feasible, initiate lisinopril at a lower dose. Monitor BP and orthostatic symptoms after the first dose.
What happens
Reduction of blood pressure
Interaction Deep Dive
When an ACE inhibitor is started in a patient already receiving diuretics, blood pressure may drop excessively3. Cases of severe postural hypotension have been documented following the addition of ACE inhibitors to diuretic regimens. This effect has been noted more frequently with loop diuretics, yet first dose hypotension occurs commonly in individuals who are sodium depleted or hypovolemic as a result of diuretics or restricted sodium intake. Typically, this hypotensive reaction is transient6271. To reduce the likelihood of hypotensive effects, the diuretic may be reduced or stopped, or salt intake may be raised, prior to beginning ACE inhibitor therapy. Should these steps not be feasible, lower the initial dose of the ACE inhibitor3.
Why it happens (mechanism)
Vasodilation and relative intravascular volume depletion
How to manage this interaction
This is a manageable situation your care team handles routinely. Keep taking both medicines exactly as prescribed unless told otherwise.
- Your team may lower or briefly hold the diuretic, or suggest adjusting salt intake, before starting lisinopril.
- If that isn't possible, they may start lisinopril at a lower dose and individualize it for you.
- They may monitor your blood pressure more closely, especially after the first dose.
Stand up slowly for the first few days and tell your pharmacist or doctor if you feel dizzy, lightheaded, or faint. Ask them before making any changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A randomized crossover study (N=19) examining the simultaneous use of hydrochlorothiazide and enalapril in older patients (62 to 84 years) found that the pharmacokinetics of enalapril remained relatively unchanged by hydrochlorothiazide, whereas 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, together with a lower proportion of the perindopril dose excreted as perindoprilat in the urine, has been documented when perindopril and hydrochlorothiazide are given together 5.
Common questions
Can I take Lisinopril and Buthiazide together?
Combining lisinopril with the diuretic buthiazide can cause an extra, usually temporary drop in blood pressure, especially with the first doses; your care team can prevent problems by adjusting doses and monitoring you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Buthiazide 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 Buthiazide interaction managed?
This is a manageable situation your care team handles routinely. Keep taking both medicines exactly as prescribed unless told otherwise. Your team may lower or briefly hold the diuretic, or suggest adjusting salt intake, before starting lisinopril. If that isn't possible, they may start lisinopril at a lower dose and individualize it for you. They may monitor your blood pressure more closely, espe… 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 Buthiazide 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 Lisinopril
Keep reading about Buthiazide
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