Dextromethorphan × Moclobemide

Moclobemide inhibits monoamine oxidase (MAO), mainly type A, and slows the breakdown of noradrenaline, dopamine and serotonin (moclobemide summary of product characteristics, SmPC, section 5.1). Dextromethorphan combined with drugs that affect serotonin metabolism, MAO inhibitors included, has caused life-threatening serotonin syndrome (dextromethorphan SmPC, section 4.4). According to the dextromethorphan SmPC, severe reactions with MAO inhibitors, moclobemide among them, may also result from slower breakdown of dextromethorphan in the liver (section 4.5). Moclobemide inhibits MAO reversibly, and its half-life is about 3 hours (moclobemide SmPC, sections 5.1 and 5.2). Even so, the dextromethorphan SmPCs require a 14-day interval after stopping any MAO inhibitor, moclobemide included (sections 4.3 and 4.5).

When combined with dextromethorphan, monoamine oxidase (MAO) inhibitors, moclobemide included, have caused serotonin syndrome with agitation, sweating, rigidity and hypertension (dextromethorphan summary of product characteristics, SmPC, section 4.5). According to the SmPC of dextromethorphan orodispersible tablets, nausea, coma, hypotension, leg tremor, muscle spasms and hyperpyrexia can also occur, up to myocardial infarction and death (section 4.5). Serotonin syndrome may include changes in mental state, autonomic instability, neuromuscular abnormalities and gastrointestinal symptoms (dextromethorphan and moclobemide SmPCs, section 4.4). Isolated cases of serious central nervous system adverse reactions have occurred after moclobemide and dextromethorphan were taken together (moclobemide SmPC, section 4.5).

The combination is contraindicated. The moclobemide summary of product characteristics (SmPC) lists dextromethorphan (section 4.3). The dextromethorphan SmPCs name moclobemide among the monoamine oxidase inhibitors, or MAOIs (sections 4.3 and 4.5). The over-the-counter dextromethorphan label of the US Food and Drug Administration (FDA) also rules out the combination. Do not take dextromethorphan within 14 days after stopping moclobemide (dextromethorphan SmPCs, sections 4.3 and 4.5; FDA dextromethorphan label). Cough and cold medicines may contain dextromethorphan. Patients taking moclobemide are told not to use them without checking first, and cough is treated with products that do not contain dextromethorphan (moclobemide SmPC, sections 4.4 and 4.5). Patients who are not sure whether a prescription drug is an MAOI are advised to check before taking dextromethorphan (FDA dextromethorphan label). If serotonin syndrome is suspected, stop dextromethorphan (dextromethorphan SmPCs, section 4.4) and, depending on the severity of symptoms, reduce the moclobemide dose or stop moclobemide as well (moclobemide SmPC, section 4.4). Benzodiazepines can be used for seizures, and benzodiazepines with external cooling for hyperthermia caused by serotonin syndrome (dextromethorphan SmPCs, section 4.9).