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

Olmesartan (Benicar) is generally well-tolerated on its own, but it can interact with a number of other medications, supplements, and substances. Some of these interactions are serious and require you to avoid the combination entirely. Others simply need monitoring. Here's what you need to know.

Major Drug Interactions: Avoid These Combinations

1. Aliskiren (Tekturna) — Contraindicated in Diabetes or CKD

Aliskiren is another blood pressure medication that works at an earlier point in the renin-angiotensin system. Combining it with olmesartan is contraindicated (forbidden) in patients with diabetes or chronic kidney disease (GFR < 60 mL/min/1.73 m²). The combination significantly increases the risk of hypotension (dangerously low blood pressure), hyperkalemia (high potassium), and acute renal failure. Even in patients without diabetes, this combination should generally be avoided.

2. ACE Inhibitors (Lisinopril, Enalapril, Ramipril) — Dual RAAS Blockade

Combining an ARB like olmesartan with an ACE inhibitor is called dual RAAS blockade. This combination is generally discouraged because it significantly increases the risk of hypotension, hyperkalemia, and kidney failure without providing additional cardiovascular benefit over either drug alone. Most guidelines recommend against this combination.

Moderate Drug Interactions: Use With Caution

3. NSAIDs (Ibuprofen, Naproxen, Aspirin at High Doses)

Nonsteroidal anti-inflammatory drugs (NSAIDs) — including ibuprofen (Advil, Motrin), naproxen (Aleve), and high-dose aspirin — can reduce the blood-pressure-lowering effect of olmesartan. More importantly, in patients who are elderly, volume-depleted, or have kidney disease, the combination can cause acute renal failure. NSAIDs cause the kidneys to retain sodium and water, which works against olmesartan's mechanism. Use acetaminophen (Tylenol) for pain management when possible if you take olmesartan.

4. Potassium Supplements and Potassium-Sparing Diuretics

Because olmesartan reduces aldosterone (which normally causes potassium excretion), it can cause potassium levels to rise. Combining olmesartan with potassium supplements, potassium-containing salt substitutes, or potassium-sparing diuretics (spironolactone, triamterene, amiloride) can push potassium dangerously high (hyperkalemia). Always tell your doctor if you take any of these.

5. Lithium

ARBs including olmesartan can increase serum lithium levels, potentially causing lithium toxicity. If you take lithium for bipolar disorder or another condition, your doctor will need to monitor lithium levels more closely when starting or adjusting olmesartan. Signs of lithium toxicity include tremor, confusion, excessive thirst, and unusual tiredness.

6. mTOR Inhibitors (Sirolimus, Everolimus, Temsirolimus)

Patients taking mTOR inhibitors (used in organ transplant or cancer treatment) have an increased risk of angioedema when combined with ARBs like olmesartan. While this combination may be necessary in some patients, prescribers should be aware of the risk and monitor for signs of angioedema (swelling of the face, throat, or airways).

7. Colesevelam (Welchol)

Colesevelam is a bile acid sequestrant used to lower cholesterol and blood sugar. It can reduce the absorption of olmesartan when taken together. To avoid this interaction, take olmesartan at least 4 hours before colesevelam.

8. Other Blood Pressure Medications (Additive Hypotension)

Taking olmesartan with other antihypertensive medications can produce additive blood pressure-lowering effects — which can be intentional (combination therapy) or can cause blood pressure to fall too low. Common medications that add to olmesartan's effect include diuretics (hydrochlorothiazide, furosemide), calcium channel blockers (amlodipine), and beta-blockers. Your doctor will manage dosing carefully when combining these.

Foods and Supplements That Interact With Olmesartan

Potassium-rich salt substitutes (NoSalt, Nu-Salt): Many salt substitutes contain potassium chloride instead of sodium chloride. Combined with olmesartan's potassium-sparing effect, this can raise potassium to dangerous levels. Ask your doctor before using salt substitutes.

Alcohol: Alcohol can lower blood pressure and may enhance olmesartan's hypotensive effect, increasing the risk of dizziness or fainting. Moderate alcohol consumption is generally okay but avoid excessive drinking.

Herbal supplements (hawthorn, garlic, licorice): Hawthorn and garlic supplements can have blood-pressure-lowering effects that add to olmesartan. Licorice root can raise blood pressure and reduce olmesartan's effectiveness. Always tell your doctor about any herbal supplements.

What to Tell Your Doctor and Pharmacist

Before starting olmesartan, tell your prescriber and pharmacist about all medications — prescription, over-the-counter, vitamins, and herbal supplements. Pay particular attention to mentioning: diabetes medications, diuretics, pain relievers, kidney medications, transplant or cancer drugs, and any supplements. Your pharmacist can run an interaction check at any time.

Also read: Olmesartan Side Effects: What to Expect and When to Call Your Doctor

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