FDA Approves Tapentadol ER for Diabetic Neuropathy

August 29, 2012 — The US Food and Drug Administration (FDA) has approved tapentadol extended-release (ER) (Nucynta, Janssen Pharmaceuticals, Inc) for the management of neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults for whom a continuous opioid analgesic is required over an extended time.

It is the first opioid to receive this indication, the company notes in a statement today.

DPN, the most common type of neuropathy, affects an estimated 16% of the more than 25 million Americans who have diabetes. The condition is often unreported and untreated, with an estimated 2 out of 5 cases not receiving care.

Tapentadol ER is already approved for the treatment of moderate to severe chronic pain in adults requiring a continuous opioid analgesic for an extended period. It is a centrally acting synthetic analgesic, although the exact mechanism of action is unknown, the release states.

"Although the clinical relevance is unclear," the company notes, preclinical studies showed that it acts as both a mu-opioid receptor and a norepinephrine reuptake inhibitor.

Better Pain Control

The supplemental New Drug Application for this indication was based on data from 2 randomly assigned withdrawal, placebo-controlled phase 3 trials showing that among patients who had at least a 1-point reduction in pain intensity during 3 weeks of treatment with tapentadol ER, those who continued on the same dose titrated to balance individual tolerability and efficacy (100 to 250 mg twice daily) for an additional 12 weeks experienced significantly better pain control compared with those who switched to placebo.

The research also demonstrated that tapentadol ER was generally well tolerated. The most common adverse reactions, affecting 10% or more of treated patients, were nausea, constipation, vomiting, dizziness, headache, and somnolence.

Approval of the drug for this indication "represents the ongoing commitment of Janssen to bring new and innovative products to patients and physicians for the management of pain," comments Paul Chang, vice president of medical affairs at Janssen Pharmaceuticals, Inc, in the press release.

Currently, 2 drugs (duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, and pregabalin, an anticonvulsant) are approved in the United States for the management of pain associated with DPN.

However, alternative treatments are needed, according to the press statement. Because the complex pathophysiology of DPN involves both central and peripheral nervous mechanisms, some patients with DPN may require treatment with multiple agents, it notes.

Evidence-Based Guidelines

Evidence-based guidelines on the treatment of painful diabetic neuropathy, released last year at the 63rd Annual Meeting of the American Academy of Neurology in Honolulu, Hawaii, and published in Neurology, noted that some opioids, including dextromethorphan, morphine sulfate, tramadol, and oxycodone, met criteria for "Moderate Evidence, Level B" endorsement.

The guideline authors noted that the use of opioids for chronic nonmalignant pain has "gained credence over the last decade" because of the studies reviewed in their document. However, both tramadol and dextromethorphan are associated with substantial adverse events, including sedation with both agents, and nausea and constipation with tramadol. Use of these agents can also be associated with the development of novel pain syndromes, such as rebound headache, the authors note, and long-term use can lead to tolerance and frequent escalation of dose.

Also receiving "Moderate Evidence, Level B" endorsement from the guideline authors were the anticonvulsant drugs gabapentin and sodium valproate, and the antidepressants amitriptyline, venlafaxine, and duloxetine.

The guidelines, developed in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation, also provide direction on the use of nonpharmacologic treatments for painful neuropathy.