Summary

Escitalopram and fluconazole can interact to increase the risk of QT interval prolongation and potentially life-threatening cardiac arrhythmias. This interaction occurs through fluconazole's inhibition of CYP2C19, leading to increased escitalopram levels and enhanced cardiac effects.

Introduction

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for major depressive disorder and generalized anxiety disorder. It works by blocking serotonin reuptake in the brain, improving mood and reducing anxiety symptoms. Fluconazole is a triazole antifungal medication used to treat various fungal infections, including candidiasis, cryptococcal meningitis, and dermatophyte infections. It works by inhibiting fungal cytochrome P450 enzymes, particularly 14α-demethylase, disrupting ergosterol synthesis in fungal cell membranes.

Mechanism of Interaction

The interaction between escitalopram and fluconazole occurs through multiple mechanisms. Fluconazole is a potent inhibitor of CYP2C19, the primary enzyme responsible for escitalopram metabolism. When fluconazole inhibits this enzyme, escitalopram clearance decreases significantly, leading to elevated plasma concentrations. Additionally, both medications have the potential to prolong the QT interval independently. Escitalopram can block cardiac potassium channels, while fluconazole may also affect cardiac conduction. The combination of increased escitalopram levels and the additive cardiac effects creates a heightened risk for QT prolongation and torsades de pointes.

Risks and Symptoms

The primary clinical risk of combining escitalopram and fluconazole is significant QT interval prolongation, which can lead to torsades de pointes, a potentially fatal ventricular arrhythmia. Patients may experience symptoms such as dizziness, fainting, palpitations, or sudden cardiac death in severe cases. The risk is particularly elevated in patients with pre-existing cardiac conditions, electrolyte imbalances (hypokalemia, hypomagnesemia), or those taking other QT-prolonging medications. Additional risks include enhanced serotonergic effects due to increased escitalopram levels, potentially leading to serotonin syndrome, though this is less common. Elderly patients and those with hepatic impairment face increased vulnerability to these interactions.

Management and Precautions

When this combination cannot be avoided, close monitoring is essential. Obtain a baseline ECG and monitor QT intervals regularly during concurrent therapy. Check and correct electrolyte imbalances, particularly potassium and magnesium levels. Consider reducing the escitalopram dose by 50% when initiating fluconazole therapy, and monitor for both efficacy and adverse effects. Educate patients about symptoms of cardiac arrhythmias and advise them to seek immediate medical attention if they experience dizziness, fainting, or palpitations. Alternative antifungal agents with less CYP2C19 inhibition, such as terbinafine for appropriate indications, should be considered when possible. If fluconazole is discontinued, gradually increase escitalopram back to the original dose while monitoring for depression or anxiety symptom recurrence.

Escitalopram interactions with food and lifestyle

Alcohol: Escitalopram may increase the effects of alcohol and impair mental and motor skills. Patients should avoid or limit alcohol consumption while taking escitalopram as recommended by clinical guidelines and major drug databases. The combination can increase sedation, dizziness, and may worsen depression symptoms.

Fluconazole interactions with food and lifestyle

Fluconazole can be taken with or without food as food does not significantly affect its absorption. However, patients should avoid excessive alcohol consumption while taking fluconazole, as both substances can potentially affect liver function. While moderate alcohol intake is generally considered acceptable, patients with liver conditions or those taking fluconazole for extended periods should discuss alcohol use with their healthcare provider. No specific dietary restrictions are required with fluconazole therapy.