Selegiline × Tramadol

Selegiline inhibits monoamine oxidase type B (MAO-B) (selegiline SmPC). The selegiline SmPC warns that above the recommended 10 mg a day it may lose its selectivity for MAO-B, and the US Food and Drug Administration (FDA) selegiline label says that selectivity may be incomplete even at the recommended dose. Tramadol is an opioid that inhibits noradrenaline reuptake and enhances serotonin release (tramadol SmPC). The FDA label for selegiline in Parkinson's disease reports serious, sometimes fatal reactions when opioids, tramadol included, were combined with MAO inhibitors, including selective MAO-B inhibitors. The FDA tramadol label specifies that this interaction presents as serotonin syndrome or opioid toxicity, and that MAO inhibitors raise the risk of seizures on tramadol.

Serotonin syndrome: agitation, hallucinations, confusion, fever, tachycardia, labile blood pressure, hyperreflexia, muscle rigidity, incoordination, nausea, vomiting, diarrhoea (FDA tramadol label). 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 selegiline SmPC prohibits selegiline with opioids, and the US Food and Drug Administration (FDA) selegiline labels name tramadol directly. The Spanish and FDA tramadol labels contraindicate tramadol in patients who are taking MAO inhibitors or have taken them within the last 14 days, and selegiline is an MAO-B inhibitor (selegiline SmPC). So tramadol is started no earlier than 14 days after selegiline is stopped (tramadol labels; FDA label for selegiline in Parkinson's disease). For the reverse switch, the FDA label for transdermal selegiline requires waiting 4 to 5 half-lives of the drug and its active metabolites after the last tramadol dose, about one week. 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).