Fluoxetine and Propafenone interaction

Fluoxetine and Propafenone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Propafenone (propafenone hydrochloride) label · effective 2026-01-29

Major

• Avoid use with other antiarrhythmic agents or drugs that prolong the QT interval.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Fluoxetine Concomitant administration of propafenone and fluoxetine in extensive metabolizers increased the S-propafenone C max and AUC by 39% and 50% respectively and the R-propafenone C max and AUC by 71% and 50%, respectively.

Drug interactionsnames FluoxetineView label on DailyMed
Moderate

It may also worsen premature ventricular contractions or supraventricular arrhythmias, and it may prolong the QT interval.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Use with Drugs that Prolong the QT Interval and Antiarrhythmic Agents The use of propafenone hydrochloride extended-release capsules in conjunction with other drugs that prolong the QT interval has not been extensively studied.

Warnings and precautionsby drug classView label on DailyMed
Minor

Such drugs may include many antiarrhythmics, some phenothiazines, tricyclic antidepressants, and oral macrolides.

Warnings and precautionsby drug classView label on DailyMed

From the Fluoxetine (Prozac) label · effective 2026-01-08

Moderate

Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution.

Drug interactionsby drug classView label on DailyMed
Minor

Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs).

Drug interactionsnames PropafenoneView label on DailyMed
Minor

…mesoridazine, droperidol,); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus)…

Warnings and precautionsby drug classView label on DailyMed
Minor

…mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.