Background: Tapentadol is a novel, centrally-acting analgesic for the treatment of acute and chronic pain with a dual mode of action: µ-agonism and noradrenaline reuptake inhibition. Pain patients often develop stress-related gastrointestinal erosions and may therefore receive proton pump inhibitors (eg, omeprazole) in addition to tapentadol.

Methods: A randomized 2-way crossover study to determine the effects of coadministration of omeprazole on the pharmacokinetics of tapentadol was conducted in 32 healthy adults aged 25 to 55 years. Treatments were (A) single oral dose of tapentadol IR 80mg or (B) oral omeprazole 40mg once daily for 4 consecutive days followed by a single dose of tapentadol 80mg 2 hours after the last dose of omeprazole. Safety and tolerability were also assessed. The study design was approved by an institutional review board at each site and all patients provided written informed consent before their enrollment.

Results: Mean tapentadol serum concentration-time profiles were similar for tapentadol alone or with omeprazole suggesting no significant influence of omeprazole on the rate or extent of tapentadol absorption. The 90% confidence intervals (CI) of treatment ratios (tapentadol/omeprazole versus tapentadol alone) for the systemic exposure (AUC) were within the 80% to 125% limits, only C_max was slightly below the lower limit (90% CI: 78.30%-100.04%). In addition, the kinetics of the main metabolite tapentadol-O-glucuronide remained unchanged upon co-administration of omeprazole. Tapentadol was well tolerated in both treatment groups. The most common adverse events included dizziness, headache, somnolence, nausea, and vomiting.

Conclusions: The results indicate that the coadministration of tapentadol and omeprazole does not lead to clinically relevant changes in the pharmacokinetics of tapentadol. Thus, no special instructions are warranted for their concomitant use.