Summary

Quetiapine and fluconazole have a clinically significant drug interaction that increases the risk of QT interval prolongation and potentially life-threatening cardiac arrhythmias. This interaction occurs through fluconazole's inhibition of CYP3A4, leading to increased quetiapine plasma concentrations.

Introduction

Quetiapine is an atypical antipsychotic medication primarily used to treat schizophrenia, bipolar disorder, and major depressive disorder as adjunctive therapy. It belongs to the dibenzothiazepine class and works by blocking dopamine and serotonin receptors. Fluconazole is a triazole antifungal medication commonly prescribed for treating candidiasis, cryptococcal infections, and other fungal infections. 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 quetiapine and fluconazole occurs through cytochrome P450 enzyme inhibition. Fluconazole is a potent inhibitor of CYP3A4, the primary enzyme responsible for quetiapine metabolism. When fluconazole inhibits CYP3A4, it significantly reduces quetiapine clearance, leading to increased plasma concentrations and prolonged half-life. This pharmacokinetic interaction can result in enhanced quetiapine effects, including increased risk of QT interval prolongation, sedation, and other adverse effects. Both drugs independently carry risks for QT prolongation, making their combination particularly concerning for cardiac safety.

Risks and Symptoms

The primary clinical risk of combining quetiapine and fluconazole is significant QT interval prolongation, which can lead to torsades de pointes, a potentially fatal ventricular arrhythmia. Increased quetiapine levels may also cause enhanced sedation, orthostatic hypotension, extrapyramidal symptoms, and metabolic effects including hyperglycemia and weight gain. Patients with pre-existing cardiac conditions, electrolyte imbalances, or those taking other QT-prolonging medications face heightened risks. The interaction is considered major and requires careful clinical assessment before concurrent use.

Management and Precautions

When concurrent use is necessary, implement comprehensive cardiac monitoring including baseline and follow-up ECGs to assess QT interval changes. Consider quetiapine dose reduction (typically 25-50%) and monitor for signs of toxicity including excessive sedation, dizziness, and cardiac symptoms. Correct any electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, before initiating therapy. Evaluate alternative antifungal agents with lower CYP3A4 inhibition potential when clinically appropriate. Educate patients about symptoms requiring immediate medical attention, including palpitations, syncope, or severe dizziness. Regular clinical follow-up is essential throughout concurrent therapy.

Quetiapine interactions with food and lifestyle

Quetiapine should not be taken with alcohol as it can increase the risk of drowsiness, dizziness, and impaired coordination. Grapefruit juice may increase quetiapine levels in the blood and should be avoided. Patients should be cautious when driving or operating machinery due to potential sedation effects. Smoking may decrease quetiapine effectiveness, and patients should discuss smoking cessation with their healthcare provider.

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.