Drug Interactions between fluoxetine and Tambocor

MONITOR: Coadministration with certain selective serotonin reuptake inhibitors (SSRIs) may increase the plasma concentrations of antiarrhythmic agents that are metabolized by CYP450 2D6 such as encainide, flecainide, mexiletine, and propafenone. The mechanism is decreased drug clearance due to inhibition of the isoenzyme by some SSRIs. The interaction has been studied specifically with fluoxetine and propafenone. In nine healthy 2D6-extensive metabolizers, fluoxetine pretreatment (20 mg once a day for 10 days) significantly increased the elimination half-life, peak plasma concentration (Cmax), and area under the concentration-time curve (AUC) of both the S- and R-enantiomers of propafenone (400 mg single dose). Oral clearance decreased by about 34% for both enantiomers. In vitro inhibition data suggest that fluoxetine and paroxetine have the most significant effects on 2D6 metabolism of propafenone, while fluvoxamine and sertraline have only modest effects.

MANAGEMENT: Caution is advised if certain SSRIs, particularly fluoxetine or paroxetine, must be used concomitantly with antiarrhythmic agents that are metabolized by CYP450 2D6. Lower initial dosages of the antiarrhythmic agent may be appropriate. Patients who are already stabilized on their antiarrhythmic regimen should be monitored for altered effects on myocardial conduction following addition or discontinuation of SSRI therapy (up to 2 weeks for most SSRIs and 5 weeks for fluoxetine due to its long half-life), and the antiarrhythmic dosage adjusted if necessary. Alternatively, an antidepressant that does not interfere with 2D6 metabolism may be considered, such as citalopram, escitalopram, or venlafaxine.

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