Drug Interactions between citalopram and voriconazole

ADJUST DOSE: Coadministration with CYP450 2C19 inhibitors may increase the plasma concentrations of citalopram, which is partially metabolized by the isoenzyme. In 12 healthy subjects who had received citalopram 40 mg once a day for 21 days, administration of cimetidine 400 mg twice a day for 8 days increased the steady-state citalopram peak serum concentration (Cmax) and systemic exposure (AUC) by 39% and 43%, respectively. In addition to inhibiting CYP450 2C19, cimetidine is also an inhibitor of CYP450 2D6 and 3A4, both of which participates in the metabolism of citalopram. The extent to which sole inhibitors of CYP450 2C19 may inhibit citalopram metabolism is unknown. Clinically, high plasma levels of citalopram may increase the risk of QT interval prolongation and torsade de pointes arrhythmia. In a randomized, double-blind, crossover, escalating multiple-dose study consisting of 119 healthy subjects, the maximum mean increase in corrected QT interval from placebo was 8.5 msec for citalopram 20 mg and 18.5 msec for citalopram 60 mg. Based on the established exposure-response relationship, prolongation of the corrected QT interval was estimated to be 12.6 ms for citalopram 40 mg. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of ventricular arrhythmia in association with QT prolongation is largely unpredictable, but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia).

MANAGEMENT: Given the risk of dose-dependent QT prolongation, citalopram dosage should not exceed 20 mg/day when prescribed in combination with CYP450 2C19 inhibitors such as cimetidine, esomeprazole, etravirine, felbamate, fluconazole, lansoprazole, letrozole, modafinil, omeprazole, oxcarbazepine, ticlopidine, and voriconazole. Alternatives should be considered when possible, and hypokalemia or hypomagnesemia should be corrected prior to initiation of citalopram treatment and periodically monitored. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, irregular heartbeat, shortness of breath, or syncope.