page_title: Tapentadol
section_title: History
hierarchical_section_title: Tapentadol / History
caption_attribution_description: English: Brand name 75 mg Nucynta (tapentadol) tablets from Janssen Pharmaceuticals.
context_page_description: Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor. Analgesia occurs within 32 minutes of oral administration, and lasts for 4–6 hours.
  It is similar to tramadol in its dual mechanism of action; namely, its ability to activate the mu opioid receptor and inhibit the reuptake of norepinephrine. Unlike tramadol, it has only weak effects on the reuptake of serotonin and is a significantly more potent opioid with no known active metabolites. Tapentadol is not a pro-drug and therefore does not rely on metabolism to produce its therapeutic effects; this makes it a useful moderate-potency analgesic option for patients who do not respond adequately to more commonly used opioids due to genetic disposition, as well as providing a more consistent dosage-response range among the patient population.
  The potency of tapentadol is somewhere between that of tramadol and morphine, with an analgesic efficacy comparable to that of oxycodone despite a lower incidence of side effects.
context_section_description: Tapentadol was invented at the German pharmaceutical company Grünenthal in the late 1980s led by Helmut Buschmann; the team started by analyzing the chemistry and activity of tramadol, which had been invented at the same company in 1962.  Tramadol has several enantiomers, and each forms metabolites after processing in the liver.  These tramadol variants have varying activities at the μ-opioid receptor, the norepinephrine transporter, and the serotonin transporter, and differing half-lives, with the metabolites having the best activity.  Using tramadol as a starting point, the team aimed to discover a single molecule that minimized the serotonin activity, had strong μ-opioid receptor agonism and strong norepinephrine reuptake inhibition, and would not require metabolism to be active; the result was tapentadol.
  In 2003 Grünenthal partnered with two Johnson & Johnson subsidiaries, Johnson & Johnson Pharmaceutical Research and Development and Ortho-McNeil Pharmaceutical to develop and market tapentadol; Johnson & Johnson had exclusive rights to sell the drug in the US, Canada, and Japan while Grünenthal retained rights elsewhere.   In 2008 tapentadol received FDA approval; in 2009 it was classified by DEA as a Schedule II drug, and entered the US market.  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.
  In 2010 Grünenthal granted Johnson & Johnson the right to market tapentadol in about 80 additional countries.  Later that year, tapentadol was approved in Europe.  In 2011, Nucynta ER, an extended release formulation of tapentadol, was released in the United States for management of moderate to severe chronic pain and received FDA approval the following year for the treatment of neuropathic pain associated with diabetic peripheral neuropathy.
  After annual sales of $166 million, in January 2015, Johnson & Johnson sold its rights to market tapentadol in the US to Depomed for $1 billion. The drug was manufactured at a plant located on the island of Puerto Rico that was hit by Hurricane Maria in 2017 causing a major shortage in the drug's availability.  In January 2018 Depomed sold off the manufacturing of the drug and licensed it to Collegium Pharmaceutical for $10 million up front with an annual royalty payment of a minimum $135 million for the next 4 years.  This combination of events has caused additional short supply of the drug leaving patients who depend on it to seek alternative treatments.
  Tapentadol is only marketed in countries where appropriate controls exist. Since 2009 the drug has been categorized in the US as a Schedule II narcotic with ACSCN 9780; in 2014 it was allocated a 17,500 kilogram aggregate manufacturing quota. In 2010, Australia made tapentadol an S8 controlled drug. The following year, tapentadol was classified as a Class A controlled drug in the United Kingdom, and was also placed under national control in Cyprus, Estonia, Finland, Greece, Latvia and Spain. More recently, Canada made the opioid a Schedule I controlled drug. After performing a critical review, the United Nations Expert Committee on Drug Dependence in 2014 advised that tapentadol not be placed under international control but remain under surveillance. In India (except the state of Punjab), multiple brands of Tapentadol remain available over the counter. Recent reports have suggested increasing tapentadol abuse and dependence in India, where, users have improvised injections with 50 and 100 mg tablets.
caption: 75 mg Nucynta (tapentadol) tablets
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