Summary

Paroxetine significantly inhibits the metabolism of flecainide through CYP2D6 enzyme inhibition, leading to increased flecainide plasma concentrations and elevated risk of cardiac arrhythmias. This interaction requires careful monitoring and potential dose adjustments when these medications are used together.

Introduction

Flecainide is a Class IC antiarrhythmic medication primarily used to treat and prevent serious ventricular arrhythmias and atrial fibrillation. It works by blocking sodium channels in cardiac tissue to stabilize heart rhythm. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression, anxiety disorders, and panic disorder. It functions by increasing serotonin levels in the brain to improve mood and emotional regulation.

Mechanism of Interaction

The interaction between flecainide and paroxetine occurs through cytochrome P450 enzyme inhibition. Paroxetine is a potent inhibitor of the CYP2D6 enzyme, which is responsible for approximately 80% of flecainide metabolism in extensive metabolizers. When paroxetine inhibits CYP2D6, it significantly reduces flecainide clearance, leading to increased plasma concentrations and prolonged half-life of the antiarrhythmic drug. This pharmacokinetic interaction can result in flecainide levels reaching potentially toxic ranges.

Risks and Symptoms

The primary clinical risk of this interaction is increased flecainide toxicity, which can manifest as serious cardiac complications including prolonged QRS duration, heart block, ventricular arrhythmias, and potentially fatal proarrhythmic effects. Patients may experience symptoms such as dizziness, blurred vision, nausea, tremor, and cardiac conduction abnormalities. The risk is particularly elevated in patients who are extensive CYP2D6 metabolizers, as they rely heavily on this pathway for flecainide elimination. This interaction is considered clinically significant and requires immediate attention.

Management and Precautions

When concurrent use is necessary, flecainide dosage should be reduced by approximately 50% and patients require close cardiac monitoring with regular ECGs to assess QRS duration and rhythm. Plasma flecainide levels should be monitored, with therapeutic levels typically maintained between 0.2-1.0 mg/L. Alternative antidepressants with minimal CYP2D6 inhibition, such as sertraline or citalopram, should be considered when possible. If paroxetine is discontinued, flecainide doses may need gradual upward adjustment as enzyme activity returns to baseline over 1-2 weeks. Patients should be educated about symptoms of flecainide toxicity and advised to seek immediate medical attention for cardiac symptoms.

Flecainide interactions with food and lifestyle

Flecainide should be taken consistently with regard to meals - either always with food or always on an empty stomach - as food can affect absorption and blood levels. Patients should avoid excessive caffeine intake as it may worsen arrhythmias. Alcohol should be used with caution as it can increase the risk of cardiac side effects and may interfere with the drug's effectiveness in controlling heart rhythm. Smoking cessation is recommended as smoking can affect flecainide metabolism and reduce its effectiveness.

Paroxetine interactions with food and lifestyle

Alcohol: Paroxetine may increase the sedative effects of alcohol. Patients should avoid or limit alcohol consumption while taking paroxetine, as the combination can enhance drowsiness, dizziness, and impair cognitive and motor functions. This interaction is consistently warned against in clinical guidelines due to the potential for increased central nervous system depression.