Adding SSRIs or SNRIs to Tapentadol Does Not Increase Adverse Events

LAS VEGAS, NV — Vincent Brett, MS, PharmD, of Janssen Scientific Affairs, Raritan, NJ, and colleagues presented a post-hoc analysis of pooled safety data at PAINWeek 2012, and found that adding tapentadol to selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) resulted in no clinically relevant adverse drug interactions.

Pooled safety data from 11 randomized, double-blind, placebo-controlled Phase 3 trials was analyzed to identify potential pharmacodynamic drug interactions associated with using tapentadol concomitantly with an SSRI or SNRI. A total of seven of the studies compared oral immediate-release tapentadol with placebo for 3–10 days for acute pain, while four of the studies compared tapentadol extended-release (ER) over 15 weeks for chronic pain.

Though 3,269 patients received tapentadol and 1,901 received placebo, the safety data was only analyzed from the 310 patients who took SSRI, the 31 who took SNRI, and the 4 patients who took both. A total of 345 patients were analyzed, and they were all taking an antidepressant (e.g., fluoxetine, paroxetine, sertraline, citalopram, escitalopram, venlafaxine, or duloxetine) at baseline. The analysis accounted for the established safety profile of SSRIs/SNRIs to assess if adding tapentadol (vs. adding placebo) to SSRI or SNRI therapy changed the safety profile.

Nausea, vomiting, dry mouth, dizziness, somnolence, pruritus, hyperhidrosis, and hot flush had higher incidences (P<0.05) among subjects taking tapentadol with an SSRI/SNRI (n=208) vs. placebo with an SSRI/SNRI (n=137). These adverse events (AEs) had incidences similar to that listed in the tapentadol labeling. Other AEs also had higher rates for subjects taking tapentadol with an SSRI/SNRI vs. placebo with an SSRI/SNRI, but most of these AEs were expected based on data for patients taking tapentadol alone. Pharyngolaryngeal pain (P=0.045), abdominal pain (ns), and myalgia (ns) were unexpected AEs, with rates >2% for subjects taking tapentadol with an SSRI/SNRI.

The investigators concluded that new, clinically relevant adverse drug interactions were not identified from this post-hoc analysis of pooled clinical trial data.