What are the potential drug interactions between fluconazole (Diflucan) and citalopram (Celexa)?

From the Guidelines

Fluconazole (Diflucan) and citalopram (Celexa) can interact, potentially increasing the risk of heart rhythm problems, and patients taking Celexa should generally not exceed 20mg daily when also taking Diflucan. When taken together, fluconazole can inhibit the metabolism of citalopram by blocking the CYP3A4 and CYP2C19 enzymes, leading to higher blood levels of citalopram, as noted in the context of drug interactions with SSRIs 1. This combination may increase the risk of QT interval prolongation, a heart rhythm abnormality that can cause serious complications including Torsades de Pointes, a potentially life-threatening arrhythmia.

Key Considerations

• Citalopram may cause QT prolongation associated with Torsade de Pointes, ventricular tachycardia, and sudden death at daily doses exceeding 40 mg/d, and should be avoided in patients with long QT syndrome 1.
• SSRIs, especially citalopram, may interact with drugs that prolong the QT interval, which is a concern when co-administered with fluconazole.
• Common symptoms of this interaction may include dizziness, fainting, palpitations, or irregular heartbeat.
• Patients with pre-existing heart conditions, electrolyte abnormalities, or those taking other medications that prolong QT interval are at higher risk.

Clinical Recommendations

• If both medications are necessary, healthcare providers should monitor the patient closely, possibly with ECG monitoring, and consider dose adjustments.
• Alternative antidepressants or antifungals with lower interaction potential might be considered depending on the specific clinical situation.
• Medical education, training, and experience are necessary to safely and effectively prescribe antidepressant medications, especially when considering potential drug interactions 1.

From the Research

Potential Drug Interactions

• The concomitant use of fluconazole and citalopram may lead to life-threatening serotonin toxicity due to the inhibition of CYP2C19 by fluconazole, resulting in increased levels of citalopram 2.
• Citalopram is a substrate for CYP2C19, and its metabolism may be inhibited by fluconazole, leading to excessive serotonergic activity 2, 3.
• The risk of serotonin toxicity may be increased when citalopram is co-administered with fluconazole, and patients should be monitored for signs of toxicity, such as mental-status changes, autonomic hyperactivity, and neuromuscular abnormalities 2, 3.

Mechanism of Interaction

• Fluconazole inhibits the CYP2C19 enzyme, which is responsible for the metabolism of citalopram, leading to increased levels of the drug and potentially causing serotonin toxicity 2.
• The inhibition of CYP2C19 by fluconazole may result in a decrease in the clearance of citalopram, leading to increased plasma concentrations and an increased risk of adverse effects 2.

Clinical Consequences

• The concomitant use of fluconazole and citalopram may lead to serious adverse effects, including serotonin toxicity, which can be life-threatening 2, 3.
• Patients who are taking citalopram and are prescribed fluconazole should be closely monitored for signs of serotonin toxicity, and the dose of citalopram may need to be adjusted or the drug discontinued 2.
• The frequency of potential azole-drug interactions, including those involving fluconazole, is high in hospitalized patients, but the clinical consequences of these interactions may be limited 4.