11 Amiodarone Interactions: Antibiotics, Statins, and More

Amiodarone (Pacerone) is a prescription medication that helps manage irregular heart rhythms. It’s effective, but it has a long list of interactions to be aware of. This is because amiodarone is broken down by enzymes in the liver, and it also affects how those enzymes process other medications.

One big concern with amiodarone is that it usually stays in the body months after stopping it. This means interactions can happen even after you’re no longer taking the medication.

Amiodarone interactions summary

Amiodarone can interact with many medications and substances. Be sure to share your medication list with your healthcare team. And keep them updated with any changes. They can check for potential interactions and manage them before you start taking amiodarone.

This isn’t a comprehensive list. But here are examples of medications and substances that can interact with amiodarone:

• Lithium (Lithobid)

• Tricyclic antidepressants (TCAs), such as amitriptyline

• Fluoroquinolone antibiotics, such as ciprofloxacin (Cipro)

• Macrolide antibiotics, like azithromycin (Zithromax)

• Azole antifungals, such as fluconazole (Diflucan)

• Digoxin (Lanoxin)

• Beta blockers, including metoprolol (Lopressor, Toprol XL), carvedilol (Coreg), and propranolol

• Calcium channel blockers, such as verapamil and diltiazem (Cardizem)

• Clonidine (Catapres)

• Ivabradine (Corlanor)

• Grapefruit juice

• Cimetidine (Tagamet HB)

• Ritonavir (Norvir)

• Sofosbuvir (Sovaldi)

• St. John’s wort

• Other antiarrhythmics

• Cyclosporine (Gengraf, Neoral, Sandimmune)

• Cholestyramine (Locholest, Prevalite)

• Certain statins, including atorvastatin (Lipitor), simvastatin (Zocor, FloLipid), and lovastatin (Altoprev)

• Warfarin (Jantoven)

• Phenytoin (Dilantin, Phenytek)

• Fentanyl

Below, we’ll review 11 notable amiodarone interactions in more detail.

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1. Antiarrhythmics

Amiodarone is an antiarrhythmic medication. Combining it with other antiarrhythmics can cause a dangerously slow heart rate (bradycardia) and irregular heart rhythms.

Antiarrhythmics that can interact with amiodarone include:

• Flecainide

• Dofetilide (Tikosyn)

• Dronedarone (Multaq)

• Quinidine

• Procainamide

Healthcare professionals usually avoid combining antiarrhythmics unless it’s absolutely necessary. In this case, they’ll closely monitor your heart rate and rhythm to identify issues if they occur.

2. Heart medications

Some heart medications also lower your heart rate, which can overlap with amiodarone’s effects. When combined with amiodarone, your heart rate can slow down too much. This can lead to symptoms such as fatigue, dizziness, and shortness of breath.

Heart medications that can interact with amiodarone include:

• Digoxin

• Beta blockers such as metoprolol, carvedilol, and propranolol

• Calcium channel blockers such as verapamil and diltiazem

• Clonidine

• Ivabradine

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In addition to affecting heart rate, amiodarone can increase digoxin levels in the body. This can increase the risk of digoxin toxicity, which can be life-threatening.

If you need to take one of these medications with amiodarone, your prescriber may use lower doses to minimize potential risks. If you’re taking digoxin, they’ll likely want to keep a close eye on the levels of digoxin in your blood. In other cases, they may recommend alternative medications that don’t interact.

3. Some antibiotics

Amiodarone can prolong the QT interval — the time it takes your heart to reset between beats. Certain antibiotics can also have this effect, increasing the risk of life-threatening abnormal heart rhythms. Some of these antibiotics can also slow the breakdown of amiodarone in the body, raising the risk of side effects.

Antibiotics that can interact with amiodarone include:

• Fluoroquinolone antibiotics, such as ciprofloxacin, levofloxacin, and moxifloxacin (Avelox)

• Macrolide antibiotics, such as azithromycin, clarithromycin (Biaxin XL), and erythromycin (Ery-Tab)

Because of these risks, healthcare professionals typically avoid combining these antibiotics with amiodarone. They’ll likely prescribe a safer alternative that doesn’t have these interactions.

4. Some antivirals

Some antiviral medications, particularly those that treat HIV, hepatitis C, or COVID-19, block the liver enzymes that break down amiodarone. This can lead to higher levels and more side effects.

Antivirals that can interact with amiodarone are available on their own and in combination with other medications. Examples of these include:

• Ritonavir

• Nirmatrelvir / ritonavir (Paxlovid)

• Lopinavir / ritonavir (Kaletra)

• Sofosbuvir

• Sofosbuvir / velpatasvir (Epclusa)

• Ledipasvir / sofosbuvir (Harvoni)

• Sofosbuvir / velpatasvir / voxilaprevir (Vosevi)

If you need an antiviral medication, your prescriber will help make sure your regimen is safe to take.

5. Tricyclic antidepressants (TCAs)

TCAs are a class of older antidepressant medications. Similar to amiodarone, they can prolong the QT interval. Taking them with amiodarone can increase the risk of life-threatening abnormal heart rhythms.

TCAs that may interact with amiodarone include:

• Amitriptyline

• Nortriptyline (Pamelor)

It’s recommended to avoid this combination. If you’re considering an antidepressant, there are many other effective options available. Your prescriber will likely choose one that doesn’t have this interaction.

6. St. John’s wort

St. John’s wort is an herbal supplement with many interactions. It boosts liver enzymes that break down many medications, including amiodarone. This can make amiodarone less effective. It’s best to avoid taking St. John’s wort with amiodarone.

7. Some statins

Statins are widely prescribed to lower cholesterol and reduce the risk of heart attacks and strokes. But some statins are broken down by the same liver enzymes that amiodarone blocks. When taken together, amiodarone can raise statin levels, increasing the risk of muscle pain and damage.

Statins that can interact with amiodarone include:

• Simvastatin

• Lovastatin

• Atorvastatin

If you take one of these statins with amiodarone, your prescriber will likely adjust your statin dose or switch you to a different statin. Be sure to report any unexplained muscle pain or dark urine, which could be a sign of muscle damage.

8. Lithium

Lithium is a mood stabilizer used to treat bipolar disorder. It’s another medication that can prolong the QT interval, especially in cases of lithium toxicity. 

Taking lithium with amiodarone may increase the risk of life-threatening abnormal heart rhythms. Additionally, both medications can affect thyroid function. Using them together may increase the risk of thyroid problems.

For these reasons, it’s recommended to avoid this combination unless absolutely necessary.

9. Warfarin

Warfarin is a blood thinner that helps prevent and treat unwanted blood clots. But it can raise the risk of bleeding. Amiodarone blocks liver enzymes that break down warfarin. This can increase warfarin levels and make bleeding more likely.

If you take both medications, your prescriber will likely lower your warfarin dose. They’ll also monitor your blood work more closely to ensure your dose is safe and effective. If you stop taking amiodarone later on, your warfarin dose may need to be readjusted. This is because amiodarone can linger in the body for a long time.

10. Phenytoin

Phenytoin is an anti-seizure medication. It’s known to interact with many medications, including amiodarone. Amiodarone blocks liver enzymes that break down phenytoin. This can cause phenytoin levels to rise and increase the risk of side effects.

It’s best to avoid this combination. But if both medications are needed, your prescriber will likely monitor your phenytoin levels and adjust the dose accordingly.

11. Grapefruit juice

Grapefruit juice is known to interfere with how certain medications are broken down in the liver, including amiodarone. It can raise amiodarone levels in the body. This increases the risk of side effects, such as abnormal heart rhythms.

Because of this, your prescriber may recommend avoiding grapefruit juice while taking amiodarone.

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Written by:

Austin Ulrich, PharmD, BCACP

​​Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. Ulrich’s experience includes direct patient care in hospital and community pharmacies.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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