Zestril Drug Interactions: What to Avoid and What to Tell Your Doctor

Zestril (lisinopril) interacts with many other medications, supplements, and foods. Some interactions are serious and could put you at risk for dangerously high potassium, low blood pressure, kidney damage, or other complications. Here's what you need to know about the most important lisinopril drug interactions in 2026.

According to drugs.com, there are 428 known drug interactions with lisinopril — 44 of which are classified as major. This guide covers the most clinically significant ones.

Major Drug Interactions: Do Not Combine

• Sacubitril/Valsartan (Entresto): Do NOT take Zestril within 36 hours before or after taking Entresto. Both drugs affect the RAAS system and both increase bradykinin, which can cause life-threatening angioedema. The FDA issued a specific warning about this combination.
• Aliskiren (Tekturna) in diabetes: If you have diabetes, do not combine Zestril with aliskiren. This combination causes increased risk of low blood pressure, high potassium, and kidney damage. The combination should also be avoided in patients with kidney disease (GFR < 60 mL/min).
• mTOR inhibitors (everolimus, sirolimus, temsirolimus): Taking lisinopril with mTOR inhibitors (used in cancer treatment and organ transplant) significantly increases the risk of angioedema.

High-Risk Interactions: Use with Caution

• NSAIDs (ibuprofen, naproxen, aspirin, diclofenac, meloxicam, celecoxib): NSAIDs reduce lisinopril's blood pressure-lowering effect. In elderly patients or those with kidney disease, NSAIDs combined with lisinopril can cause acute kidney injury. This is a very common interaction — many patients take both without realizing the risk. Talk to your doctor about alternatives for pain management.
• Potassium-sparing diuretics (spironolactone, triamterene, amiloride): Combining these with lisinopril can cause dangerously high potassium levels (hyperkalemia). Both lisinopril and potassium-sparing diuretics raise potassium independently. This combination is sometimes used intentionally in heart failure, but requires close potassium monitoring.
• Potassium supplements and salt substitutes: Salt substitutes (like Nu-Salt or NoSalt) contain potassium chloride instead of sodium chloride. Combined with lisinopril's potassium-raising effect, this can cause hyperkalemia. Always tell your doctor if you use a salt substitute.
• Lithium: Lisinopril causes the kidneys to excrete more sodium, which can interfere with how the body clears lithium, leading to lithium toxicity. Signs of lithium toxicity include confusion, blurry vision, and muscle weakness — a medical emergency. If you take lithium, your doctor should monitor your lithium levels closely when starting lisinopril.
• ARBs (losartan, valsartan, irbesartan, etc.): Do not take an ACE inhibitor and an ARB together. This "dual RAS blockade" does not provide added benefit for most conditions, but significantly increases the risk of hyperkalemia, low blood pressure, and acute kidney injury.

Moderate Interactions: Monitor Carefully

• Insulin and sulfonylureas (glipizide, glimepiride, glyburide): Lisinopril may increase insulin sensitivity, enhancing the blood sugar-lowering effect of diabetes medications and potentially causing hypoglycemia (low blood sugar). Monitor blood glucose more closely when starting lisinopril if you take diabetes medication.
• Other antihypertensives: Taking lisinopril with other blood pressure medications (diuretics, beta-blockers, calcium channel blockers) will lower blood pressure more than either drug alone. This is often intentional in combination therapy, but watch for signs of low blood pressure: dizziness, fainting, lightheadedness.
• Gold injections (sodium aurothiomalate): Used in rheumatoid arthritis treatment. Combining with ACE inhibitors can cause nitritoid reactions: facial flushing, nausea, vomiting, and low blood pressure.

Foods and Supplements to Watch

• High-potassium foods in excess: Bananas, oranges, potatoes, avocados, spinach, tomatoes. Lisinopril already raises potassium — eating large amounts of very high-potassium foods regularly can push levels too high, especially in patients with kidney disease.
• Alcohol: Alcohol can lower blood pressure and may worsen dizziness and lightheadedness side effects of lisinopril. Moderate alcohol use is generally acceptable, but talk to your doctor about your specific situation.
• Herbal supplements: Some herbal supplements can affect blood pressure or potassium levels. Always tell your doctor and pharmacist about any supplements you take, including herbal products.

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What to Tell Your Doctor Before Starting Zestril

Before starting Zestril, make sure your doctor knows about:

• All prescription medications, including other blood pressure drugs
• All OTC medications, especially NSAIDs (ibuprofen, naproxen)
• Vitamins and supplements, including potassium and herbal products
• Any use of salt substitutes
• Your history of angioedema from any medication
• Whether you are pregnant, plan to become pregnant, or are breastfeeding

For a full overview of what side effects to watch for, see our guide on Zestril side effects.