Moclobemide × Tramadol

Moclobemide reversibly inhibits monoamine oxidase (MAO), mainly subtype A, and slows the breakdown of serotonin, noradrenaline and dopamine (moclobemide SmPC). Tramadol is an opioid that inhibits noradrenaline reuptake and enhances serotonin release (tramadol SmPC). Together they can cause life-threatening serotonin syndrome. The tramadol SmPC warns of a second risk: patients who received MAO inhibitors before the opioid pethidine had life-threatening reactions affecting the nervous system, breathing and circulation, and the same reactions cannot be ruled out with tramadol. The US Food and Drug Administration (FDA) tramadol label adds that MAO inhibitors raise the risk of seizures on tramadol.

Serotonin syndrome: agitation, hallucinations, confusion, fever, tachycardia, labile blood pressure, hyperreflexia, myoclonus, muscle rigidity, incoordination, nausea, vomiting, diarrhoea (moclobemide and tramadol labels). Seizures may occur. The interaction of MAO inhibitors with opioids can also present as opioid toxicity: respiratory depression up to coma (FDA tramadol label).

The combination is contraindicated. The moclobemide SmPC prohibits it with tramadol by name. The tramadol SmPC contraindicates tramadol in patients who are taking MAO inhibitors or have taken them within the last 14 days, and the US Food and Drug Administration (FDA) tramadol label sets the same 14-day ban. So tramadol is started no earlier than 14 days after the last moclobemide dose (tramadol labels). The FDA tramadol label also says not to start an MAO inhibitor while taking tramadol. If a patient has received both drugs, watch for signs of serotonin syndrome and stop tramadol at once if it is suspected (FDA tramadol label). Withdrawal of the serotonergic drugs usually brings rapid improvement (tramadol SmPC).