Drug Interactions Between Diltiazem, Digoxin, Xarelto, Metformin & Jardiance

In our latest question and answer, our pharmacist discusses drug interactions between different cardiac medications.


Can I take Diltiazem 480mg a day and Digoxin 125 mg a day and Xarelto 20mg a day for atrial fibrillation. I am now short of breath, have swollen legs and STILL average 115 ppm. Then add in Metformin 500 x 4 a day and Jardiance (Empagliflozin) 10mg a day for Diabetes 2.  It sounds like a toxic mix to me and no one will look at the whole picture for me.

Asked by Emhian On Dec 04, 2017

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Dec 06, 2017

First of all, it may be best to speak with your cardiologist in regards to your symptoms of shortness of breath, rapid heart rate, and swollen legs. These may be signs of heart failure and/or worsening of atrial fibrillation and should be assessed as soon as possible.

In regards to the drug interactions, it is important to discuss your concerns with your physician, as they should have the complete information necessary to make informed treatment decisions. Below we will discuss potential drug interactions between the medications that you have listed.


Interaction Between Diltiazem And Digoxin

Both diltiazem and digoxin can be used to help treat atrial fibrillation and have an impact on heart rate control. Diltiazem is a calcium channel blocker that helps to lower heart rate. Digoxin is a cardiac glycoside that helps control ventricular heart rate in patients with atrial fibrillation.

Diltiazem decreases the clearance of digoxin from your body by inhibition of P-glycoprotein, which helps removes digoxin from cells in the body. In effect, the amount of digoxin is increased in your blood and could lead to an increased risk of digoxin toxicities, like GI side effects and visual disturbances.

With that being said, at times these medications are sometimes used together to improve control of heart rate. It may be a good idea to ask your doctor about monitoring of your digoxin levels, as these can help decide the dose of digoxin that you will need.


Interaction Between Diltiazem And Empagliflozin

Diltiazem and other calcium channel blockers can cause increases in blood glucose levels. Assuming your blood glucose is well controlled on metformin and empagliflozin, it may be necessary to take diltiazem even as a diabetic patient.


Interaction Between Diltiazem And Xarelto (Rivaroxaban)

Diltiazem may increase the concentration of Xarelto by a similar mechanism that it increases digoxin levels. Because Xarelto depends on P-glycoprotein and CYP3A4, both inhibited by diltiazem, Xarelto is not cleared as well. This is riskier in patients with worsened kidney function. Since Xarelto is a blood thinner used to prevent the risk of stroke, this could lead to an increased risk for bleeding. While on blood thinners of any sort, it is important to monitor for signs of bleeding including dark stools, severe upset stomach, and extreme fatigue. 

About the Pharmacist

Dr. Kevin Davis Pharm.D

Dr. Kevin Davis is a licensed pharmacist with experience in retail and hospital pharmacy. He graduated from the University of Florida with a Doctor of Pharmacy degree in 2015 and a Master of Healthcare Administration degree from Adventist University in 2017. He is also a Board Certified Pharmacotherapy Specialist since 2016.

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