Citalopram × Fluvoxamine

Fluvoxamine strongly inhibits CYP2C19 and, to a lesser degree, CYP3A4 and CYP2D6 (fluvoxamine SmPC), and citalopram is cleared by all three: about 38% via CYP2C19, 31% via CYP3A4 and 31% via CYP2D6 (citalopram SmPC). Citalopram levels rise, and its QT prolongation is dose-dependent, so the US Food and Drug Administration (FDA) caps citalopram at 20 mg/day with any CYP2C19 inhibitor. Both drugs are serotonergic, and the fluvoxamine SmPC warns that the combination can lead to a life-threatening serotonin syndrome.

Serotonin syndrome: agitation, hallucinations, delirium up to coma; tachycardia, labile blood pressure, dizziness, sweating, hyperthermia; tremor, rigidity, myoclonus, hyperreflexia, incoordination; seizures; nausea, vomiting, diarrhoea. Higher citalopram levels prolong the QT interval: dizziness, palpitations, syncope and, in severe cases, torsade de pointes.

The labels do not ban the pair, but it is used with limits. While the patient takes fluvoxamine, the citalopram dose stays at or below 20 mg/day (US Food and Drug Administration (FDA) citalopram label). The fluvoxamine SmPC requires such drugs to be started at the lower end of the dose range with monitoring for adverse effects, and the Spanish citalopram SmPC asks for caution with fluvoxamine. Potassium and magnesium are corrected before citalopram is started (citalopram SmPC). If serotonin syndrome develops, both drugs are stopped at once and supportive treatment is started (citalopram FDA label). If signs of arrhythmia appear, citalopram is stopped and an electrocardiogram (ECG) is done (citalopram SmPC).