Important Drug Interactions for the Abnormal Heart Rhythm Drug Amiodarone

Patients taking the abnormal heart rhythm drug amiodarone (PACERONE) should be aware that it has clinically important and potentially dangerous interactions with many other prescription medications. Importantly, such drug interactions with amiodarone can occur months after a patient stops taking amiodarone because substantial amounts of the drug remain in the body for several weeks to months after discontinuing treatment with it.[1]

Amiodarone is approved by the Food and Drug Administration (FDA) for treatment of documented recurrent life-threatening abnormal heart rhythms known as ventricular fibrillation and ventricular tachycardia in adults who have not responded to or have not tolerated other available drugs used to treat these abnormal heart rhythms.[2] The FDA-approved product labeling for amiodarone includes a black-box warning indicating that the drug can cause serious, potentially fatal lung and liver toxicity and, paradoxically, can exacerbate the abnormal heart rhythms that it is intended to treat.

Increased risk of fatal heart rhythm abnormalities [3],[4]

Amiodarone can cause prolongation of the QT interval in the heart rhythm. QT prolongation is a change in the electrical activity of the heart that may lead to a potentially fatal heart rhythm disturbance called torsades de pointes, which can cause cardiac arrest and sudden death.

Numerous oral drugs, when used concomitantly (at the same time) with amiodarone, can further increase the risk of QT prolongation (see the Table, below, for examples).The list of such drugs includes certain medications for treating Alzheimer’s disease, bacterial infections, depression, fungal infections, HIV infection and psychosis, among others. In many cases, the interacting drug also causes QT prolongation, beyond that caused by amiodarone alone.

For many of these drugs, the risk of QT prolongation and potentially fatal abnormal heart rhythms is so high that they should not be taken concomitantly with amiodarone.

Examples of Oral Drugs That Increase the Risk of Dangerous Heart Rhythms When Taken Concomitantly With Amiodarone

†Brand-name combination products were excluded.
*Designated as Do Not Use by Worst Pills, Best Pills News
**Designated as Limited Use by Worst Pills, Best Pills News

Other important drug interactions[5],[6]

Anticoagulants (blood thinners)

Concomitant use of amiodarone and the anticoagulant warfarin (JANTOVEN) can dramatically increase the anticoagulant effects of warfarin and the risk of potentially fatal bleeding complications. Ideally, concomitant use of these two drugs should be avoided. If such use is unavoidable, the dose of warfarin generally needs to be decreased upon initiation of amiodarone and increased upon discontinuation of amiodarone. More frequent monitoring of warfarin levels also should occur, especially during initiation and discontinuation of amiodarone.

Likewise, amiodarone can inhibit the breakdown and removal from the body of the so-called “novel” oral anticoagulant rivaroxaban (XARELTO), which we have designated as Do Not Use. As a result, concomitant use of amiodarone with rivaroxaban can result in significantly increased blood levels of rivaroxaban and an increased risk of bleeding complications.

Cholesterol-lowering statins

Like many drugs, amiodarone can inhibit the activity of substances in the liver called enzymes that metabolize (break down or chemically modify) other drugs. For example, amiodarone can inhibit the liver enzymes that break down certain cholesterol-lowering statin drugs — including atorvastatin (LIPITOR), lovastatin (ALTOPREV) and simvastatin (FLOLIPID, ZOCOR). Concomitant use of amiodarone with these statins can increase the blood levels of the statin drugs and, thereby, the risk of statin-induced myopathy (muscle damage). In severe cases, this condition can progress to rhabdomyolysis, a life-threatening, muscle-destroying condition that can lead to sudden kidney failure and death. Patients taking statin drugs who are prescribed amiodarone may need to have their statin dose reduced or switch to a different cholesterol-lowering treatment.

Digoxin (LANOXIN)

Concomitant use of amiodarone and digoxin — which is used to treat heart failure and to control heart rate in patients with atrial fibrillation (a common abnormal heart rhythm characterized by an irregular and often rapid heartbeat) — can result in increased and potentially highly toxic blood levels of digoxin. Common symptoms of digoxin toxicity are loss of appetite, nausea, vomiting and fatigue. Digoxin toxicity can lead to abnormal heart rhythms. If concomitant use of amiodarone and digoxin is unavoidable, more frequent monitoring of blood digoxin levels should occur, especially during initiation and discontinuation of amiodarone.

Fentanyl (ACTIQ, DURAGESIC, FENTORA, LAZANDA, SUBSYS)

Concomitant use of amiodarone and the opioid analgesic fentanyl may result in heart toxicity, resulting in low blood pressure, decreased heart rate and decreased pumping of blood by the heart, and an increased risk of fentanyl toxicity, leading to decreased consciousness and depressed breathing.

Phenytoin (DILANTIN, PHENYTEK)

Concomitant use of amiodarone and the seizure drug phenytoin may result in increased blood phenytoin levels and phenytoin toxicity. Symptoms of phenytoin toxicity include loss of muscle coordination, involuntary repetitive eye movements, slurred speech, sleepiness and confusion. Because of the potential harm that may result from this interaction, phenytoin blood levels should be monitored when a patient starts or stops treatment with amiodarone.

What You Can Do

If you need treatment with amiodarone, review all your other medications with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with amiodarone, you may need to reduce the dosage of the interacting drug or to take an alternative drug for your abnormal heart rhythm, or your doctor may advise you to stop the interacting drug.

Be aware that you can be susceptible to important amiodarone-related drug interactions for several weeks to months after stopping the drug and that many other drugs not listed in this article also may have potentially dangerous interactions with amiodarone.
 

References

[1] Advagen Pharma Limited. Label: amiodarone. February 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d911b4cf-eec4-43f8-aa64-cc60cfc901b9&type=display. Accessed May 6, 2021.

[2] Ibid.

[3] Ibid.

[4] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “amiodarone.” Accessed April 19, 2021.

[5] Advagen Pharma Limited. Label: amiodarone. February 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d911b4cf-eec4-43f8-aa64-cc60cfc901b9&type=display. Accessed May 6, 2021.

[6] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “amiodarone.” Accessed April 19, 2021.