Summary

Citalopram and fluconazole can interact through CYP2C19 enzyme inhibition, potentially increasing citalopram levels and risk of QT interval prolongation. This interaction requires careful monitoring and possible dose adjustments to prevent serious cardiac complications.

Introduction

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression and anxiety disorders. It works by blocking the reuptake of serotonin in the brain, improving mood and emotional regulation. 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, disrupting ergosterol synthesis in fungal cell membranes.

Mechanism of Interaction

The interaction between citalopram and fluconazole occurs primarily through cytochrome P450 enzyme inhibition. Fluconazole is a potent inhibitor of CYP2C19 and moderate inhibitor of CYP3A4, enzymes responsible for citalopram metabolism. When fluconazole inhibits these enzymes, citalopram clearance decreases, leading to increased plasma concentrations. Both drugs also have the potential to prolong the QT interval independently, and their combination may have additive effects on cardiac conduction, increasing the risk of torsades de pointes and other serious arrhythmias.

Risks and Symptoms

The primary clinical risk of combining citalopram and fluconazole is QT interval prolongation, which can lead to potentially fatal cardiac arrhythmias such as torsades de pointes. Increased citalopram levels may also intensify serotonergic side effects, including nausea, dizziness, drowsiness, and in rare cases, serotonin syndrome. Patients with pre-existing cardiac conditions, electrolyte imbalances (particularly hypokalemia or hypomagnesemia), or those taking other QT-prolonging medications face elevated risks. The interaction is considered clinically significant and requires active management to ensure patient safety.

Management and Precautions

When concurrent use is necessary, consider reducing citalopram dose by 50% and monitor closely for signs of toxicity. Obtain baseline and follow-up ECGs to assess QT interval changes, especially in high-risk patients. Monitor electrolyte levels (potassium, magnesium) and correct any imbalances before and during treatment. Watch for increased serotonergic side effects and cardiac symptoms such as palpitations, syncope, or dizziness. Consider alternative antifungal agents with lower CYP inhibition potential when clinically appropriate. If QT prolongation exceeds 500 ms or increases by more than 60 ms from baseline, discontinue or further reduce citalopram dosing. Consult cardiology for patients with significant cardiac risk factors.

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.