What Happens When You Take Lisinopril and Aliskiren Together

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)

What You Should Do

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.

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Frequently Asked Questions

Can I take Lisinopril and Aliskiren together?

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.

What are the side effects of the Lisinopril and Aliskiren interaction?

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.

Should I talk to my doctor about taking Lisinopril and Aliskiren?

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.

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