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

Enalapril is known to interact with over 400 different medications, with 44 of those classified as major interactions. This does not mean you cannot take enalapril with other drugs — many interactions are manageable with monitoring or dose adjustments. But it does mean that your prescriber and pharmacist need to know everything you take, including over-the-counter medications, supplements, and vitamins.

Here are the most clinically important drug interactions with enalapril.

Major Interactions: Combinations to Avoid or Use With Extreme Caution

1. Sacubitril/Valsartan (Entresto) — Do Not Combine

Do not take enalapril within 36 hours before or after taking sacubitril/valsartan (Entresto). Combining these drugs dramatically increases the risk of angioedema — sudden and potentially life-threatening swelling of the face, lips, tongue, or throat. This 36-hour washout requirement is a hard contraindication, not just a caution.

2. Aliskiren (Tekturna) in Diabetes — Contraindicated

Combining enalapril with aliskiren (another blood pressure drug that works at the renin stage of the RAAS) in diabetic patients is contraindicated. This combination carries a high risk of kidney failure, dangerously low blood pressure, and severe hyperkalemia. It should also be avoided in patients with reduced kidney function (GFR less than 60 mL/min).

3. Potassium-Sparing Diuretics — High Risk of Hyperkalemia

Combining enalapril with potassium-sparing diuretics such as spironolactone (Aldactone), amiloride, or triamterene significantly increases the risk of hyperkalemia (dangerously high potassium). Both drug types raise potassium through different mechanisms, and together the effect is additive. If this combination is necessary (common in heart failure management), close potassium and kidney monitoring is essential.

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4. Potassium Supplements and Salt Substitutes

Many people use salt substitutes (like Nu-Salt or NoSalt) to reduce sodium intake — not knowing these products contain potassium chloride instead of sodium chloride. Taking enalapril with potassium-based salt substitutes or potassium supplements can cause dangerous hyperkalemia. Always tell your doctor about any supplements you use, including electrolyte products.

5. NSAIDs (Ibuprofen, Naproxen, Aspirin) — Reduced Effectiveness and Kidney Risk

Nonsteroidal anti-inflammatory drugs (NSAIDs) — including over-the-counter products like ibuprofen (Advil, Motrin) and naproxen (Aleve) — reduce enalapril's blood pressure-lowering effect and increase kidney strain. If you regularly take NSAIDs for pain or arthritis while on enalapril, discuss safer alternatives with your doctor. Acetaminophen (Tylenol) is generally preferred for occasional pain relief in patients on enalapril.

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6. Lithium — Risk of Lithium Toxicity

Enalapril can increase lithium levels in the blood. Since lithium has a narrow therapeutic window (the difference between a therapeutic and toxic dose is small), this interaction can cause lithium toxicity. Signs of lithium toxicity include tremor, confusion, weakness, and irregular heartbeat. If you take lithium (for bipolar disorder), your doctor will monitor lithium levels carefully after starting enalapril.

Moderate Interactions: Important to Monitor

Other Antihypertensives — Additive Hypotension

Combining enalapril with other blood pressure medications (beta-blockers, calcium channel blockers, other ACE inhibitors, ARBs, or diuretics) increases blood pressure lowering. This is often intentional and beneficial, but must be managed carefully to avoid dangerous drops in blood pressure (severe hypotension), especially when starting therapy.

Insulin and Diabetes Medications — Enhanced Blood Sugar Lowering

Enalapril may enhance the blood-sugar-lowering effect of insulin and oral diabetes medications. This can sometimes cause hypoglycemia (low blood sugar), especially when starting enalapril. Diabetic patients should monitor their blood sugar more closely when initiating enalapril therapy.

What to Tell Your Doctor Before Starting Enalapril

Give your prescriber and pharmacist a complete list of all your medications, including:

All prescription medications (especially other blood pressure drugs, diuretics, and lithium)

All over-the-counter medications (particularly NSAIDs like ibuprofen and naproxen)

Vitamins and supplements (especially potassium supplements and any electrolyte products)

Any history of angioedema or allergic reactions to other ACE inhibitors (benazepril, lisinopril, ramipril, captopril, etc.)

Whether you are pregnant, may become pregnant, or are breastfeeding

For more on enalapril side effects and warning signs, see Enalapril Side Effects: What to Expect and When to Call Your Doctor. If you need help locating enalapril at a pharmacy near you, medfinder can help.