Dextromethorphan × Tranylcypromine

Tranylcypromine is an irreversible, non-selective monoamine oxidase (MAO) inhibitor; MAO is the enzyme that breaks down serotonin, noradrenaline and dopamine (tranylcypromine SmPC, section 5.1). Dextromethorphan has serotonergic effects, and together with MAO inhibitors it can cause life-threatening serotonin syndrome (dextromethorphan SmPC, section 4.4). Part of the reaction may come from slower breakdown of dextromethorphan in the liver (dextromethorphan SmPC, section 4.5). Because MAO inhibition is irreversible, enzyme activity takes 3–5 days to return after the last dose of tranylcypromine (tranylcypromine SmPC, section 5.1). Inhibition may persist for up to 10 days (US Food and Drug Administration (FDA) tranylcypromine label).

Monoamine oxidase inhibitors combined with dextromethorphan have caused serotonin syndrome with agitation, sweating, rigidity and hypertension (dextromethorphan SmPC, section 4.5). The combination has also caused nausea, coma, hypotension, leg tremor, muscle spasms and hyperpyrexia that can lead to myocardial infarction and death (dextromethorphan orodispersible tablets SmPC, section 4.5). Serotonin syndrome may include changes in mental state, autonomic instability, neuromuscular abnormalities and gastrointestinal symptoms (dextromethorphan SmPC, section 4.4). Tranylcypromine and dextromethorphan together can have life-threatening effects on the central nervous system, breathing and circulation (tranylcypromine SmPC, section 4.5). Psychosis and bizarre behaviour are also possible (US Food and Drug Administration (FDA) tranylcypromine label).

The combination is contraindicated (dextromethorphan SmPC, sections 4.3 and 4.5, which name tranylcypromine; tranylcypromine SmPC, sections 4.3 and 4.5; US Food and Drug Administration (FDA) tranylcypromine label, section 4.1). Avoid dextromethorphan for 14 days after stopping tranylcypromine (dextromethorphan SmPC, sections 4.3 and 4.5; tranylcypromine SmPC, section 4.2; FDA over-the-counter dextromethorphan label). Start tranylcypromine no earlier than 4–5 half-lives of dextromethorphan and its active metabolite after the last dose of dextromethorphan (FDA tranylcypromine label, section 7.1). Dextromethorphan is an ingredient of cough medicines (tranylcypromine SmPC, section 4.3). A patient taking tranylcypromine should therefore not use over-the-counter medicines or supplements without first asking a doctor or pharmacist (FDA tranylcypromine label, section 7.1). Nasal, cough and cold products may also contain indirect sympathomimetics, which are contraindicated with tranylcypromine because of the risk of severe hypertensive crisis (tranylcypromine SmPC, sections 4.3 and 4.5). If serotonin syndrome is suspected, stop dextromethorphan (dextromethorphan SmPC, section 4.4), stop tranylcypromine and other serotonergic drugs at once and start supportive symptomatic treatment (FDA tranylcypromine label, section 5.3).