Tapentadol is a nontraditional centrally acting analgesic agent with dual analgesic mechanism. While still an opioid it is associated with less opioid-related side effects.

Mechanism of Action

Tapentadol is a weak μ-opioid agonist and a norepinephrine reuptake inhibitor. The norepinephrine reuptake inhibition reduces pain by activation of inhibitory pain pathways. The two mechanisms of action are synergistically reducing pain.

Clinical Use: 


Tapentadol is FDA approved for the treatment of moderate to severe acute pain.

The extended-release formulation of tapentadol has been FDA approved for the treatment of chronic pain and painful diabetic peripheral neuropathy.



Tapentadol’s oral morphine equivalence factor is 0.4.

Tapentadol 50mg to 100mg compares to oxycodone 10mg to 15 mg in clinical trials comparing the analgesic effects of these drugs.

A reasonable order following surgery would be 50, 75, or 100 mg tapentadol every four to six hours.

Special Considerations: 


  • Paralytic ileus
  • Monoamine oxidase inhibitors within 14 days


  • Respiratory and CNS depression, Misuse/Abuse (it is an opioid!)
  • Serotonin Syndrome risk

Wang X, et al. Efficacy and Safety of Tapentadol Immediate Release for Acute Pain: A Systematic Review and Meta-Analysis. Clin J Pain. 2020 May;36(5):399-409.

Freynhagen R, et al. Safety of tapentadol compared with other opioids in chronic pain treatment: network meta-analysis of randomized controlled and withdrawal trials. Curr Med Res Opin. 2020 Nov 13:1-12.