Clinically Relevant Metoprolol Drug Interactions

I’ve done tons of posts on drug interactions over the years. I’ve dedicated a whole book to drug interactions in primary care AND drug-food interactions. I was recently asked about metoprolol drug interactions and which ones would I consider the most important? Here’s my list of metoprolol drug interactions that I think would be valid to memorize.

Pulse-Lowering Agents

This drug interaction is a little bit of a no-brainer and you will see patients on two agents that can reduce pulse rate. When they are two cardiovascular medications, most often, the patient will have cardiology involvement. Amiodarone, diltiazem, verapamil, and many others can contribute to bradycardia. Typically this concern is going to be monitored by checking the pulse.

One of the under-the-radar interactions involves acetylcholinesterase inhibitors. I have numerous patients with dementia who are often taking metoprolol. Acetylcholinesterase inhibitors like donepezil and rivastigmine can drop the heart rate. I pay attention when new dementia medications are started and ensure that pulse is monitored when additions or dose changes are made.


Metoprolol is significantly broken down by CYP2D6. Inevitably, drugs that inhibit or induce CYP2D6 can alter the concentration of metoprolol. When I think of CYP2D6 inhibitors, I always think of antidepressants. The most common agents that are CYP2D6 inhibitors include paroxetine, fluoxetine, and bupropion. Enzyme induction is less common but has been reported. With the classic example of rifampin, metoprolol concentrations and ultimately the effectiveness can be reduced when rifampin is added.

Blood Pressure-Lowering Interactions.

Additional blood pressure-lowering medication can have additive effects. I don’t think many have difficulty understanding that we should monitor blood pressure when a drug like lisinopril or hydrochlorothiazide is added to metoprolol. What might fly under the radar are agents that aren’t necessarily considered blood pressure-lowering agents but carry hypotension as a potential adverse effect. A good example of this is Sinemet.

Epinephrine Blunting

Beta-blockers like metoprolol can block to at least reduce the effectiveness of epinephrine used in allergic reaction management. Do we do much about this? Typically not. While it is understood that a patient who is taking metoprolol may have a reduced response to epinephrine, you would not withhold emergency treatment with an Epi-Pen if it was deemed appropriate.

Would you add anything else to your list of metoprolol drug interactions?

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Written By Eric Christianson

April 13, 2022

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