More than 25 million Americans experience acute pain each year as a result of injuries or surgery, and it’s the most common reason people seek medical attention. Several classes of medications—particularly opioids—have been historically used to treat moderate-to-severe pain, but the adverse effects of these medications can be difficult for patients to endure. Researchers are continuing to search for new medications and combinations of therapies that limit adverse effects while maximizing efficacy.

Two Mechanisms of Action

In November 2008, the FDA approved tapentadol (Nucynta, Johnson & Johnson Pharmaceutical R&D, to be marketed by PriCara, Division of Ortho-McNeil-Janssen). This new therapy, available in 50 mg, 75 mg, and 100 mg doses, is an immediate-release tablet indicated for the relief of moderate-to-severe acute pain in adults aged 18 and older. It’s a centrally acting oral analgesic that combines mu-opioid receptor agonist activity and norepinephrine reuptake inhibition. Mu-opioid agonists bind to and activate mu-opioid receptors in the central nervous system. These drugs modify sensory and affective aspects of pain and inhibit pain transmission at the spinal cord. They affect activity at parts of the brain that control how pain is perceived. Norepinephrine reuptake inhibitors, which also affect the central nervous system, are medications that increase the level of norepinephrine in the brain by inhibiting its re-absorption into nerve cells; these compounds have analgesic properties. Tapentadol provides analgesia through both of these mechanisms.

Analyzing the Data

The approval of tapentadol was based on data from clinical studies involving more than 2,100 patients. At the 2008 annual meeting of the American Pain Society, researchers presented multiple phase III studies demonstrating that tapentadol offered patients significant pain relief and was generally well tolerated. The studies were conducted in different patient groups, including those who had a bunionectomy and in those with low back pain or osteoarthritis of the hip or knee. The most common adverse events reported in clinical trials were nausea, dizziness, vomiting, somnolence, and headache, but these events were reported in significantly fewer patients who received tapentadol at any dose compared to equianalgesic doses of standard opioid therapy.

Important Considerations

Tapentadol is contraindicated in any situation where mu-opioid agonists are contraindicated, such as when patients have significant respiratory depression, acute or severe bronchial asthma, or hypercapnia. It’s also contraindicated in patients with paralytic ileus and in those currently using or within 14 days of using monoamine oxidase inhibitors. If some drugs are taken in combination with tapentadol, respiratory depression, hypotension, profound sedation, or coma may occur. When clinicians are contemplating using combined therapy, a dose reduction of one or both agents should be considered. Tapentadol should also not be used in patients who are susceptible to increased intracranial pressure, impaired consciousness, or coma.

It’s important to be cautious when prescribing tapentadol to patients with head injuries, intracranial lesions, or other sources of preexisting increased intracranial pressure as well as in patients with pancreatic or biliary tract disease or moderate hepatic impairment. Furthermore, elderly patients are more likely to have decreased renal and hepatic function. As such, it’s important to consider starting elderly patients with the lower range of recommended doses. Lastly, tapentadol could potentially be abused similarly to how other mu-opioid agonists are abused. If clinicians are concerned about an increased risk of misuse, abuse, or diversion, then an alternative medication may be necessary.