Summary

The combination of citalopram and fluconazole represents a significant drug interaction that can increase the risk of QT interval prolongation and potentially life-threatening cardiac arrhythmias. This interaction occurs because fluconazole inhibits the metabolism of citalopram, leading to elevated plasma concentrations of the antidepressant.

Introduction

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for major depressive disorder and anxiety disorders. It works by blocking the reuptake of serotonin in the brain, helping to improve mood and emotional well-being. Fluconazole is a triazole antifungal medication used to treat various fungal infections, including candidiasis, cryptococcal meningitis, and other systemic mycoses. It works by inhibiting fungal cytochrome P450 enzymes, particularly 14α-demethylase, which is essential for ergosterol synthesis in fungal cell membranes.

Mechanism of Interaction

The interaction between citalopram and fluconazole occurs through cytochrome P450 enzyme inhibition. Fluconazole is a potent inhibitor of CYP2C19 and a moderate inhibitor of CYP3A4, both of which are involved in citalopram metabolism. When fluconazole inhibits these enzymes, it significantly reduces the clearance of citalopram, leading to increased plasma concentrations of the antidepressant. This elevation in citalopram levels increases the risk of QT interval prolongation, a cardiac conduction abnormality that can predispose patients to torsades de pointes, a potentially fatal ventricular arrhythmia.

Risks and Symptoms

The primary clinical risk of combining citalopram and fluconazole is the development of QT interval prolongation and associated cardiac arrhythmias. Patients may experience symptoms such as dizziness, fainting, palpitations, or in severe cases, sudden cardiac death. The risk is particularly elevated in patients with pre-existing cardiac conditions, electrolyte imbalances (especially hypokalemia or hypomagnesemia), or those taking other QT-prolonging medications. Additional risks include increased serotonergic side effects such as nausea, headache, drowsiness, and in rare cases, serotonin syndrome when combined with other serotonergic agents.

Management and Precautions

Healthcare providers should exercise extreme caution when considering this combination and may need to avoid concurrent use entirely, especially in high-risk patients. If the combination cannot be avoided, consider reducing the citalopram dose by 50% and implementing intensive cardiac monitoring with baseline and follow-up ECGs to assess QT interval changes. Monitor electrolyte levels (potassium, magnesium, calcium) and correct any imbalances before and during treatment. Consider alternative antifungal agents with less CYP450 inhibition potential, such as terbinafine for appropriate indications, or alternative antidepressants with lower cardiac risk profiles. Patients should be counseled about the signs and symptoms of cardiac arrhythmias and advised to seek immediate medical attention if they experience chest pain, palpitations, dizziness, or fainting.

Citalopram interactions with food and lifestyle

Alcohol: Citalopram may increase the sedative effects of alcohol. Patients should avoid or limit alcohol consumption while taking citalopram as it can worsen depression symptoms and increase the risk of drowsiness, dizziness, and impaired judgment. Grapefruit: While not a major interaction, grapefruit juice may slightly increase citalopram levels in the blood. Patients should consult their healthcare provider about grapefruit consumption. MAO inhibitors and certain foods: Patients taking citalopram should avoid tyramine-rich foods (aged cheeses, cured meats, fermented foods) if they have recently discontinued or are transitioning from MAO inhibitors, though this is more relevant during the washout period between medications.

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.