Hydrochlorothiazide/Lisinopril and Aliskiren Interaction
Drug interaction information between Hydrochlorothiazide/Lisinopril and Aliskiren.
Hydrochlorothiazide/Lisinopril and Aliskiren have a documented major interaction in FDA labeling.
FDA drug labeling documents a major-severity interaction between Hydrochlorothiazide/Lisinopril and Aliskiren. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Combining these medications puts too much stress on the system that regulates blood pressure, increasing the risk of fainting and kidney damage.
What To Do
Do not use these drugs together if you have diabetes, and your doctor should check your kidney function and potassium levels closely.
FDA Label Information
Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Do not co-administer aliskiren with ZESTORETIC in patients with diabetes. Avoid use of aliskiren with ZESTORETIC in patients with renal impairment (GFR < 60 mL/min).
Hydrochlorothiazide/Lisinopril Also Interacts With
- Lisinopril minor
- Losartan minor
- Hydrochlorothiazide minor
- Spironolactone minor
- Propranolol minor
Aliskiren Also Interacts With
- Amlodipine/Benazepril major
- Amlodipine/Valsartan major
- Azilsartan major
- Benazepril major
- Candesartan major
Frequently Asked Questions
Can I take Hydrochlorothiazide/Lisinopril and Aliskiren together?
This is a major interaction. Do not use these drugs together if you have diabetes, and your doctor should check your kidney function and potassium levels closely.
How serious is the interaction between Hydrochlorothiazide/Lisinopril and Aliskiren?
This interaction is classified as "major" severity by the FDA. Major interactions may be life-threatening or cause serious side effects.
Why do Hydrochlorothiazide/Lisinopril and Aliskiren interact?
Combining these medications puts too much stress on the system that regulates blood pressure, increasing the risk of fainting and kidney damage.
Understanding the Hydrochlorothiazide/Lisinopril and Aliskiren Interaction
FDA-approved prescribing information for these two drugs flags their combination as a major-severity interaction. Hydrochlorothiazide/Lisinopril belongs to the Thiazide Diuretic / ACE Inhibitor Combination class and Aliskiren belongs to the Direct Renin Inhibitor class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Combining these medications puts too much stress on the system that regulates blood pressure, increasing the risk of fainting and kidney damage. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Hydrochlorothiazide/Lisinopril has 13 total documented interactions on file in this dataset, and Aliskiren has 28. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Do not use these drugs together if you have diabetes, and your doctor should check your kidney function and potassium levels closely. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Hydrochlorothiazide/Lisinopril or Aliskiren based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.