Moclobemide × Zolmitriptan

Moclobemide is a reversible inhibitor of monoamine oxidase A (MAO-A), the enzyme that breaks down serotonin and clears zolmitriptan and its active N-desmethyl metabolite. After moclobemide, zolmitriptan exposure (AUC) rose by 26% and the AUC of the active metabolite rose 3-fold (zolmitriptan SmPC, AEMPS, section 4.5). Zolmitriptan is a 5-HT1B/1D agonist and moclobemide raises serotonin levels, so their serotonergic effects add up. The moclobemide SmPC lists triptans among contraindicated combinations, and the FDA label of zolmitriptan contraindicates use with any MAO-A inhibitor.

The main danger is serotonin syndrome: spontaneous or inducible clonus, agitation and sweating, tremor and hyperreflexia, hypertonia with a temperature above 38 °C, confusion, swings in heart rate and blood pressure, nausea, vomiting, diarrhoea (zolmitriptan SmPC, AEMPS, and FDA label). Symptoms usually start within minutes to hours after a new or higher dose of a serotonergic drug (FDA label of zolmitriptan). Higher zolmitriptan exposure also strengthens its own effects: heaviness, pressure or tightness in the chest, throat and neck, and a rise in blood pressure.

The combination is contraindicated: the moclobemide SmPC lists triptans among contraindicated drugs and names zolmitriptan explicitly (moclobemide SmPC, AEMPS, sections 4.3 and 4.5). The FDA label of zolmitriptan contraindicates it in patients taking an MAO-A inhibitor or within 2 weeks of stopping one (FDA label of zolmitriptan, sections 4 and 7.2). The Spanish zolmitriptan SmPC is softer: with an MAO-A inhibitor it caps the dose at 5 mg per 24 hours and bans the combination only when moclobemide exceeds 150 mg twice daily (zolmitriptan SmPC, AEMPS, sections 4.2 and 4.5). The strictest document wins, so do not prescribe zolmitriptan to a patient on moclobemide. After stopping moclobemide, allow zolmitriptan no earlier than 2 weeks later (FDA label of zolmitriptan, section 4). If the patient has taken the drugs together and signs of serotonin syndrome appear, stop both serotonergic drugs. Withdrawal brings rapid improvement, and further treatment depends on the severity of symptoms (zolmitriptan SmPC, AEMPS, section 4.4; FDA label of zolmitriptan, section 5.7).