Can you take Flecainide with Sertraline? (1+ interactions)

In this article, we will explore the possible interaction between Sertraline and Flecainide. We will also discuss what side effects one may experience by combining these two medications and how to manage the side effects associated with this interaction.

Can you take Flecainide with Sertraline?

Yes, you can take Flecainide with Sertraline. Flecainide and Sertraline are two commonly prescribed medications for different medical conditions. Nevertheless, Flecainide does interact with Sertraline in terms of side effects.

Flecainide is an antiarrhythmic medication primarily used in the management of atrial fibrillation (1). Sertraline (Zoloft), on the other hand, is a widely prescribed antidepressant for the management of depressive disorders (2).

While both Flecainide and Sertraline are effective in their respective areas, they have different mechanisms of action that amplify their interactions when taken together.

Additionally, it is important to understand that while these medications may interact and cause life-threatening side effects, you can take them together, but only under the guidance of your doctor. These medications are available only by prescription, and you should only use them as directed by your healthcare provider.

What is the mechanism of Sertraline-Flecainide interaction?

Several research studies have attributed the interaction between Flecainide and Sertraline to their metabolism by the Cytochrome P450 enzymes (CYP450) and their effects on the neurotransmitters in the brain. This interaction is caused by their inhibitory and additive effects when used together.

SSRI medications such as Sertraline and Fluoxetine increase levels of Flecainide in the body through inhibition of CYP450 enzymes. Flecainide is primarily metabolized by Cytochrome P450 isoenzyme 2D6 (CYP2D6).

Sertraline inhibits this enzyme increasing levels of Flecainide and potentially causing several side effects (3,4).

Conversely, Flecainide can also increase Sertraline levels in the brain and peripheral system via inhibition of the CYP2D6 enzyme potentiating its side effects profile.

What are the factors influencing Sertraline-Flecainide interactions?

Several factors can influence the interaction between these drugs including:

  • Dosage – The dosage of both medications influences the likelihood of interactions between these medications.
  • Duration of use – Long-term use of either drug may increase the likelihood of interactions as they accumulate in the body.
  • Genetic factors – Genetic variations in CYP450 metabolizing enzymes influence how these medications are metabolised and their side effects.
  • Underlying health conditions – Certain health conditions like liver disorders can influence how drugs are metabolized and their potential interaction.

What are the potential side effects of Sertraline-Flecainide interactions?

Sertraline-flecainide interactions can vary among individuals and are dependent on individual patient factors such as genetics and their prescribed dosage.

Increased risk of QT prolongation and cardiac arrhythmias:

Both drugs carry the potential for QT interval prolongation, a condition that can trigger life-threatening irregular heart rhythms, known as cardiac arrhythmias. Combining these two medications amplifies the likelihood of developing or worsening pre-existing cardiac arrhythmias.

Serotonin syndrome:

Individually, both these medications can elevate serotonin levels. While rare, concurrent use of these two medications may increase the likelihood of Serotonin syndrome, a potentially life-threatening condition that occurs when there are excess serotonin levels in the brain. 

Serotonin syndrome can manifest with some of the side effects associated with Sertraline, including tremors, muscle rigidity, seizures and sweating. However, it can also present as agitation, confusion, rapid heart rate, fever, and, in severe cases, even coma.

How to manage the Sertraline-Flecainide interaction side effects?

While taking these two medications it is important to be cautious and take precautions against them including:

  • Symptom awareness: You should stay vigilant of any unusual symptoms while taking these medications and report them immediately.
  • Regular monitoring and assessment of symptoms: While using these medications, it is important to have frequent consultations with your primary healthcare provider. They need to closely monitor you for potential side effects and negative interactions.
  • Dose adjustments and scheduling: Your primary healthcare provider may modify the dosages of one or both medications to minimise interaction and adverse events. Additionally, your healthcare provider will determine the optimal drug schedule for dual therapy with these medications.
  • Consideration of alternative medications: In the event of a severe interaction, such as serotonin syndrome, your doctor may adjust your treatment plan by discontinuing one or both medications or switching you to alternative medications with fewer side effects.


While it is possible to take Flecainide and Sertraline together with proper precautions and monitoring, the potential risks associated with this combination necessitate open communication and close supervision by your doctor to maintain safe and effective treatment.

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Arunachalam K, Alzahrani T. Flecainide [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2023 Oct 6]. Available from:



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Mar PL, Horbal P, Chung MK, Dukes JW, Ezekowitz M, Lakkireddy D, et al. Drug Interactions Affecting Antiarrhythmic Drug Use. Circulation: Arrhythmia and Electrophysiology [Internet]. 2022 May [cited 2023 Oct 6];15(5). Available from:



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