Fluoxetine with Propafenone Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Propafenone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased propafenone exposure and an increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)

Interaction Summary

Propafenone has been shown to prolong the QTc interval. FLUoxetine has been shown to prolong the QTc interval at the recommended therapeutic dose . Concomitant use of propafenone (a CYP2D6 substrate) and FLUoxetine (a CYP2D6 inhibitor) should be avoided because concomitant use may increase propafenone exposure, cause additive effects on the QT interval, and increase the risk for ventricular arrhythmias and torsade de pointes. If concomitant use is required, obtain a baseline ECG and periodically monitor ECG during therapy. Consider discontinuation of FLUoxetine if signs or symptoms of ventricular arrhythmia occur and obtain a cardiac evaluation. Additionally, propafenone has a narrow therapeutic index. Agents that have a narrow therapeutic index should be initiated at the low end of the dosing range if the patient is already taking FLUoxetine or has used FLUoxetine in the previous 5 weeks. If FLUoxetine is initiated, consider dose reduction of the CYP2D6 substrate (eg, propafenone) . Even though no formal drug interaction studies have been done, caution is advised if drugs known to prolong the QT interval are used concomitantly. In addition, FLUoxetine may inhibit CYP2D6 and impair the metabolism of propafenone .

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Concomitant use of propafenone (a CYP2D6 substrate) and FLUoxetine (a CYP2D6 inhibitor) should be avoided because concomitant use may increase propafenone exposure, cause additive effects on the QT interval, and increase the risk for ventricular arrhythmias and torsade de pointes. Both propafenone and FLUoxetine, as single agents, prolong the QT interval. If concomitant use is required, obtain a baseline ECG and periodically monitor ECG during therapy. Consider discontinuation of FLUoxetine if signs or symptoms of ventricular arrhythmia occur and obtain a cardiac evaluation. Additionally, propafenone has a narrow therapeutic index. Agents that have a narrow therapeutic index should be initiated at the low end of the dosing range if the patient is already taking FLUoxetine or has used FLUoxetine in the previous 5 weeks. If FLUoxetine is initiated, consider dose reduction of the CYP2D6 substrate (eg, propafenone).

Mechanism Of Interaction

Inhibition of CYP2D6-mediated propafenone metabolism; additive effects on QT interval prolongation

Literature Reports

A) The metabolism of propafenone enantiomers was altered after FLUoxetine treatment in 9 healthy Chinese subjects. All subjects were extensive CYP2D6 metabolizers. Subjects received a single oral dose of propafenone 400 mg both before and after FLUoxetine 20 mg daily for ten days. The oral clearance of both S- and P- enantiomers of propafenone decreased from approximately 75 L/hr to 50 L/hr and 107 L/hr to 70 L/hr, respectively. Compared to baseline, the elimination half life, peak concentration, and area under the curve for both enantiomers after FLUoxetine therapy were significantly increased .

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Propafenone Overview

• Propafenone is used to treat arrhythmia (irregular heartbeat) and to maintain a normal heart rate. Propafenone is in a class of medications called antiarrhythmics. It works by acting on the heart muscle to improve the heart's rhythm.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.