FDA Labeling Change Cites Possibility Tramadol May Cause Serotonin Syndrome

Tramadol, marketed under the brand names Ultram and Ultracet, is a weak mu-opioid agonist, often used in pain management in lieu of stronger opioids. On September 9, 2009, the FDA added a warning on the possible association with serotonin syndrome, a potentially life threatening condition characterized by mental confusion, , agitation and hallucinations; autonomic problems such as tachycardia, labile blood pressure and hyperthermia; neuromuscular manifestations such as hyperreflexia, incoordination and ataxia; and gastrointestinal symptoms such as diarrhea, nausea and vomiting.

This syndrome may occur with Tramadol alone in usual therapeutic doses but more commonly in combination with SSRI*s. SNRI**s, MAO*** inhibitors, TCA****s and Triptans*****. Cytochrome P450 enzyme inhibitors CYP2D6 and CYP3A4 interfere with the metabolic for Tramadol and lead to serotonin buildup and toxicity.

*SSRI=selective serotonin uptake inhibitor
**SNRI= selective serotonin norepinephrine uptake inhibitor
***MAO=monoamine oxidase
****TCA=tricyclic antidepressant
*****Triptans=drugs used for migraine abortive therapy.