Combining lisinopril with aliskiren (a direct renin inhibitor) provides dual blockade of the renin-angiotensin-aldosterone system (RAAS), which increases the risk of hyperkalemia, hypotension, and acute kidney injury. This combination is contraindicated in diabetic patients.
How This Interaction Works (Mechanism)
Lisinopril blocks ACE (converting angiotensin I to angiotensin II), while aliskiren directly inhibits renin (the first step of the RAAS cascade). Dual RAAS blockade causes excessive suppression of aldosterone and angiotensin II, leading to impaired potassium excretion (hyperkalemia) and reduced renal perfusion pressure. The ALTITUDE trial demonstrated increased adverse events with dual RAAS blockade in diabetic patients with kidney disease.
Source: FDA Drug Safety Communication on RAAS Dual Blockade, 2014 (reaffirmed 2024)
This combination is contraindicated in patients with diabetes or moderate to severe renal impairment (eGFR below 60). For other patients, the combination is generally not recommended due to limited benefit and increased risk. If dual RAAS blockade is considered for severe heart failure, it should only be used under specialist supervision with frequent monitoring of potassium, creatinine, and blood pressure.
Check More Drug Interactions
Use our free interaction checker to search thousands of drug, supplement, and food combinations.
Open Interaction CheckerSources and standards behind this page
Drug coverage in the United States is governed by published rules rather than by any one insurer's summary, and the sources below are the primary ones. They are linked so a reader can check a claim without taking this page's word for it.
- FDA Orange Book publishes the therapeutic-equivalence ratings that decide whether a generic may be substituted for a brand-name drug.
- FDA generic drug facts sets out what "generic equivalent" means and what a manufacturer must prove.
- CMS prescription drug coverage defines the rules a Medicare drug plan formulary must follow and how it may change mid-year.
- Medicare.gov drug coverage (Part D) states what a Part D plan is required to offer a member.
- CMS prescription drug appeals documents the coverage-determination and exception process when a drug is denied.
- Medicare Plan Compare is the official tool for checking what a specific plan charges for a specific drug at a specific pharmacy.
- Drugs@FDA is the federal database of approved drug products, which establishes whether a covered product exists and in what form.
- DailyMed carries the current FDA labeling for every marketed drug product, including approved strengths and forms.
- MedlinePlus drug information is the National Library of Medicine's consumer reference for what a medication is and how it is used.
- FTC report on pharmacy benefit managers documents how the middlemen between an insurer and a pharmacy shape what a plan actually covers.
- National Library of Medicine maintains the drug and health databases the sources above draw on.
This page describes how coverage and formularies work. It is not medical advice, and a reader's own plan documents and prescriber decide what applies to them.
Frequently Asked Questions
Lisinopril and Aliskiren have a severe interaction and should generally not be taken together without close medical supervision. The combination can cause serious, potentially life-threatening side effects. Contact your doctor immediately if you are currently taking both medications.
Combining lisinopril with aliskiren (a direct renin inhibitor) provides dual blockade of the renin-angiotensin-aldosterone system (RAAS), which increases the risk of hyperkalemia, hypotension, and acute kidney injury. This combination is contraindicated in diabetic patients.
Yes. Anytime you are taking multiple medications, supplements, or substances, you should inform your doctor and pharmacist. They can evaluate your specific risk factors (age, kidney function, other medications, medical conditions) and determine whether the Lisinopril and Aliskiren combination is safe for you, or whether adjustments are needed.
Related Resources
- Supplement interactions with Lisinopril on Health Britannica
- Supplement interactions with Aliskiren on Health Britannica
- Lisinopril prices and pharmacy comparison on RxGrab
- Aliskiren prices and pharmacy comparison on RxGrab
- Full drug interaction checker tool
Get Drug Safety Alerts
Subscribe to receive updates on FDA warnings, new drug interactions, and patient safety information.