Clinical value of tapentadol extended-release in painful diabetic peripheral neuropathy

Abstract

Painful diabetic peripheral neuropathy is difficult to treat, partially because the underlying mechanism of pain is not fully understood. Various treatment guidelines recommend first-line agents, such as α2-δ ligands, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants but combination therapy of alternative agents including opiates is often warranted. Tapentadol extended-release has a novel dual mechanism of action; it is both a mu-opioid receptor agonist and a norephinephrine reuptake inhibitor. It has been in the spotlight since it was FDA-approved specifically for the treatment of painful diabetic peripheral neuropathy in 2012. Previous reviews of tapentadol have focused on chronic pain. The purpose of this review article is to assess the efficacy and safety of tapentadol extended-release in adult populations with painful diabetic peripheral neuropathy and provide guidance for formulary decisions.

Keywords::

• norepinephrine reuptake inhibitor
• opioid agonist
• painful diabetic peripheral neuropathy
• tapentadol extended-release

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Painful diabetic peripheral neuropathy (PDPN) occurs in approximately 16% of patients with diabetes. It is frequently undertreated even though it can contribute to significantly decreased quality of life.

• Tapentadol extended-release (ER) is a centrally acting analgesic that is US FDA-approved for the treatment of neuropathic pain associated with PDPN in adults when a continuous, around-the-clock opioid analgesic is indicated.

• A systematic literature review was performed. Economic data on tapentadol ER for PDPN were not available during our search. In this analysis, we reviewed two clinical studies in regards to the safety and efficacy of tapentadol ER in PDPN.

• Tapentadol ER demonstrated statistically significant pain reduction compared with placebo. In addition, more patients achieved clinically significant pain reduction (>30% on numerical pain rating scale) with tapentadol than placebo.

• The most common treatment-emergent adverse events (TEAEs) reported included nausea, dizziness, somnolence, constipation, vomiting and headache. More patients reported TEAEs, as well as discontinuations due to TEAEs in the treatment group as compared with the control group. No difference in opioid withdrawal was noted with either group.

• While the clinical trials had appropriate clinical end points and showed statistical significant pain reductions, neither trial reported CIs for 30% pain reduction, and there was also a lack of data on supplemental analgesia use. The exclusion of opioid non-responders from the studies limits the external validity of the results.

• The safety data lacked statistical testing, and the severity of TEAEs were not analyzed.

• While tapentadol ER has evidence to support its efficacy in the treatment of PDPN, without comparative studies to other first-line treatments, it is difficult to determine its place in therapy.