Tapentadol, sold under the brand names Nucynta and Palexia among others, is a synthetic opioid analgesic of the benzenoid class with a dual mode of action as a highly selective full agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI).

[14] It is similar to tramadol in its dual mechanism of action; namely, its ability to activate the μ-opioid receptor and inhibit the reuptake of norepinephrine.

[18] Common side effects include euphoria, constipation, nausea, vomiting, headaches, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating.

[19] Serious side effects may include addiction and dependence, substance abuse, respiratory depression and an increased risk of serotonin syndrome.

[24] In India, the Central Drug Standard Control Organisation approved tapentadol immediate-release (IR) and extended-release (ER) preparations for severe acute pain in April 2011 and December 2013 respectively.

[29] As with other μ-opioid agonists, tapentadol may cause spasms of the sphincter of Oddi, and is therefore discouraged for use in patients with biliary tract disease such as both acute and chronic pancreatitis.

[31] The most commonly reported side effects of tapentadol therapy are constipation, nausea, vomiting, headaches, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating.

[7][21] Tapentadol has also been noted to induce feelings of relaxation and euphoria,[20][32] and it may cause serious side effects such as respiratory depression, serotonin syndrome, addiction and substance dependence.

[31][36] Since these initial trials, however, evidence has shown that tapentadol is commonly abused, misused and diverted,[11] that it is addictive,[37] and that it poses a high risk of physical and/or mental dependence.

[2][9][10][38] Given that tapentadol is a highly selective full agonist of the μ-opioid receptor, and given that is not a pro-drug, with a relatively high ceiling effect, studies have found that it is significantly more abusable than tramadol,[39] and similar to hydrocodone and other full agonists of the μ-opioid receptor (such as oxycodone and hydromorphone) in terms of addiction and dependence liability.

[40][41] There have been reports of users crushing, chewing, inhaling or injecting immediate-release tapentadol tablets, which can lead to respiratory depression, coma and death.

In receptor binding studies on cloned human MOR labeled with titrated naloxone, tapentadol showed affinity with a Ki of 60 nM.

[49] In vivo, only 32% of an oral dose of tapentadol will survive first pass metabolism and proceed to the bloodstream to produce its effects on the central and peripheral nervous systems of the patient.

[51] The peak plasma concentration (Cmax; amount of active drug in the bloodstream) when taken after food is increased by 8% and 18% for tapentadol IR and ER preparations, respectively.

[57] Tapentadol was reported to be the "first new molecular entity of oral centrally acting analgesics" class approved in the United States in more than 25 years.

[65] This combination of events has caused additional short supply of the drug leaving patients who depend on it to seek alternative treatments.

Recent reports have suggested increasing Tapentadol abuse and dependence in India, where users have improvised injections with 50 and 100 mg tablets.