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

Metoprolol interacts with more than 500 medications. That's a lot — but not all interactions are equally dangerous. Many are minor and just require monitoring. Others are significant enough to require dose adjustments or avoiding certain combinations entirely. Here's what every metoprolol patient needs to know.

The Most Important Interaction: CYP2D6 Inhibitors

Metoprolol is broken down in the liver by an enzyme called CYP2D6. When you take another drug that inhibits (blocks) this enzyme, metoprolol accumulates in your body to higher levels than intended. This can dramatically increase both the effects and side effects of metoprolol — including dangerous bradycardia and low blood pressure.

Common CYP2D6 inhibitors that interact with metoprolol:

• Fluoxetine (Prozac) — Potent CYP2D6 inhibitor; can double or triple effective metoprolol levels
• Paroxetine (Paxil) — Another potent inhibitor; significant risk of excessive bradycardia when combined with metoprolol
• Bupropion (Wellbutrin, Zyban) — Moderate CYP2D6 inhibitor; may significantly elevate metoprolol levels
• Diphenhydramine (Benadryl) — The common OTC allergy/sleep medication is also a CYP2D6 inhibitor at high doses
• Amiodarone (Cordarone) — Used for arrhythmias; inhibits CYP2D6 AND has additive bradycardia effects — a high-risk combination

Cardiac Drugs with Additive Effects

Several heart medications have similar effects to metoprolol and, when combined, can cause additive slowing of the heart rate or excessive blood pressure lowering:

• Diltiazem and verapamil (calcium channel blockers): Both slow the heart and blood pressure. Combining with metoprolol can cause dangerous bradycardia or heart block. Use with caution and monitor closely.
• Digoxin (Lanoxin): Used for heart failure and atrial fibrillation. Additive slowing of heart rate. Combination is used clinically but requires monitoring.
• Clonidine (Catapres): A blood pressure medication. Special danger: if clonidine is discontinued while on metoprolol, severe rebound hypertension can occur. Always taper clonidine carefully when discontinuing.
• Other antihypertensives (lisinopril, losartan, amlodipine): These are commonly combined with metoprolol for blood pressure management. The combinations are generally safe but may cause additive hypotension, especially when starting or changing doses.

Common OTC Medications That Interact with Metoprolol

Many patients don't realize that over-the-counter medications can interfere with metoprolol:

• NSAIDs (ibuprofen, naproxen, aspirin): Can reduce metoprolol's blood pressure-lowering effect by causing sodium and water retention. May also increase cardiovascular risk. Use acetaminophen (Tylenol) for pain when possible.
• Decongestants (pseudoephedrine, phenylephrine): Found in many cold medicines. These stimulate adrenaline receptors and can raise blood pressure and heart rate, partially counteracting metoprolol's effect.
• Caffeine: Large amounts of caffeine stimulate the heart and can blunt metoprolol's heart rate-slowing effect. Moderate caffeine intake (1-2 cups/day) is generally fine.

Diabetes Medications and Blood Sugar Risk

If you take insulin or sulfonylureas (like glipizide or glyburide) for diabetes, metoprolol can mask a key symptom of low blood sugar — rapid heart rate (palpitations). You may not realize you're hypoglycemic until more severe symptoms appear. Monitor blood sugar carefully, especially during exercise or when adjusting diabetes medications.

Epinephrine (Adrenaline) — Emergency Alert

If you carry an epinephrine auto-injector (EpiPen) for severe allergies, be aware that metoprolol can blunt the cardiovascular effects of epinephrine. In an anaphylactic emergency, larger or repeated doses of epinephrine may be needed. Always carry your EpiPen and inform emergency providers that you take metoprolol.

Interactions During Surgery or Anesthesia

Always tell your surgeon and anesthesiologist that you take metoprolol before any procedure. Certain anesthetics interact with beta-blockers and can cause excessive blood pressure drops. Generally, your team will decide whether to continue metoprolol through surgery or make adjustments.

What to Tell Your Doctor

Before starting metoprolol — and at every visit — share a complete list of everything you take: all prescription medications, OTC drugs, vitamins, supplements, and herbal products. Even "harmless" supplements can interact. For more on what to watch for while taking metoprolol, see our guide on metoprolol side effects.