Data from separate studies of tramadol IR and tramadol ER (90 days and 12 weeks duration, respectively) suggest that tramadol ER has a lower propensity for adverse events than tramadol IR (Ultram PI 2004 ; Ultram ER PI 2006). The most frequently reported adverse events for tramadol IR and tramadol ER were in the CNS and the GI system (Ultram PI 2004 ; Ultram ER PI 2006). Adverse event rates – occurring with an incidence of at least 5% – were higher with tramadol IR than tramadol ER (reported above); event rates for constipation, nausea, and dizziness were 46%, 40%, and 33%, respectively, after 90 days of tramadol IR therapy (Ultram PI 2004 ; Ultram ER PI 2006). Like tramadol IR, tramadol ER has the potential for interacting with 2D6- and 3A4- inhibitors that may alter tramadol’s efficacy by lowering M1 metabolite levels or changing tramadol’s exposure (Ultram PI 2006 ). Metabolism of tramadol ER may also be compromised in patients with 2D6 gene dysfunction, which is present in approximately 8%-10% of the Caucasian population, reducing its analgesic efficacy (Gough et al 1990 ; Garcia-Quetglas et al 2007 ).