Fluvoxamine × Moclobemide

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI). Moclobemide reversibly inhibits monoamine oxidase (MAO), mainly type A, and slows the breakdown of serotonin, noradrenaline and dopamine (moclobemide summary of product characteristics, SmPC, section 5.1). Drugs that impair serotonin metabolism, that is, MAO inhibitors, increase the risk of life-threatening serotonin syndrome with SSRIs (fluvoxamine label, US Food and Drug Administration, FDA, section 5.2). Moclobemide inhibits the enzyme CYP2C19 and can raise plasma levels of fluvoxamine (moclobemide SmPC, section 4.5). Fluvoxamine in turn strongly inhibits CYP2C19, which partly breaks down moclobemide. According to the moclobemide SmPC, such changes are generally not therapeutically important and should not need a dose change (fluvoxamine and moclobemide SmPCs, section 5.2). The half-life of fluvoxamine is 13–15 hours after a single dose and 17–22 hours with repeated dosing (fluvoxamine SmPC, section 5.2).

Serotonin syndrome during fluvoxamine treatment can be life-threatening, especially with other serotonergic drugs. It brings hyperthermia, rigidity, myoclonus and autonomic instability with rapid swings in vital signs. Mental changes include confusion, irritability and extreme agitation progressing to delirium and coma (fluvoxamine summary of product characteristics, SmPC, section 4.4). When moclobemide has been combined with antidepressants, fluvoxamine among them, isolated cases of hyperthermia, confusion, hyperreflexia and myoclonus have occurred (moclobemide SmPC, section 4.5). Hallucinations, tachycardia, dizziness, sweating, flushing, tremor, incoordination, seizures, nausea, vomiting and diarrhoea are also possible (fluvoxamine label, US Food and Drug Administration, FDA, section 5.2).

The combination is contraindicated (fluvoxamine summary of product characteristics, SmPC, sections 4.3 and 4.5; fluvoxamine label, US Food and Drug Administration, FDA, section 4). The moclobemide SmPC is softer: it lists fluvoxamine among antidepressants to give with caution alongside moclobemide (moclobemide SmPC, section 4.5). The strictest document applies. The documents differ on switching intervals. The Spanish fluvoxamine SmPC names moclobemide as a reversible monoamine oxidase inhibitor (MAOI) and allows fluvoxamine to start the day after moclobemide is stopped (fluvoxamine SmPC, section 4.3). The moclobemide SmPC says the same for any antidepressant (section 4.5). The FDA label requires at least 14 days after stopping an MAOI used for psychiatric disorders (FDA fluvoxamine label, sections 2.4 and 4). When switching the other way, allow at least one week between the last dose of fluvoxamine and the first dose of an MAOI (fluvoxamine SmPC, section 4.3) or at least 14 days (FDA fluvoxamine label, sections 2.4 and 4). The moclobemide SmPC asks prescribers to consider the half-life of the previous selective serotonin reuptake inhibitor (moclobemide SmPC, section 4.5). Do not stop fluvoxamine abruptly. Taper the dose over at least one to two weeks (fluvoxamine SmPC, section 4.2). If signs of serotonin syndrome appear, stop fluvoxamine and other serotonergic drugs at once and start symptomatic treatment (fluvoxamine SmPC, section 4.4; FDA fluvoxamine label, section 5.2). Keep the patient under medical supervision and admit to hospital if needed (moclobemide SmPC, section 4.5).