Ready Conversion of Patients with Well-Controlled, Moderate to Severe, Chronic Malignant Tumor–related Pain on Other Opioids to Tapentadol Extended Release

Abstract

Background and ObjectivesThe effectiveness and tolerability of tapentadol extended release (ER), a centrally acting analgesic with μ-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have been demonstrated in patients with chronic pain, including those switching directly from prior opioid therapy. The objective of the current study was to evaluate the effectiveness and safety of conversion to oral tapentadol ER (50–250 mg twice daily) from previous around-the-clock strong opioid therapy in patients with moderate to severe, chronic malignant tumor–related cancer pain that was well-controlled.MethodsThis randomized, open-label, phase III study, which was conducted in Japan, included a 1- to 2-week screening period (on previous opioid) and an 8-week, open-label treatment period. Eligible patients, who were taking a strong opioid analgesic and had a mean pain intensity score <4 during the 3 days prior to randomization (adequate pain control on previous strong opioid), were randomized (1:1) to receive twice-daily treatment with tapentadol ER (100–500 mg/day) or morphine sustained release (SR; 20–140 mg/day; reference for assay sensitivity). Initial doses were estimated based on the conversion ratio of tapentadol ER:oxycodone:morphine:fentanyl = 10:2:3:0.03. The primary effectiveness endpoint was the proportion of patients who maintained pain control [change from baseline in mean pain intensity (11-point numerical rating scale) less than +1.5 for 3 consecutive days and no more than two doses of rescue medication per day for 3 consecutive days) during the first week of open-label treatment.ResultsIn the tapentadol ER group (n = 50), 84.0 % of patients (42/50; 95 % CI, 70.89–92.83) maintained pain control during Week 1. On the Patient Global Impression of Change, 2.1 % (1/48), 2.1 % (1/48), 22.9 % (11/48), and 50.0 % (24/48) of patients in the tapentadol ER group reported that their overall condition was “very much improved,” “much improved,” “minimally improved,” and “not changed,” respectively, at Week 1 compared with 0 %, 10.7 % (3/28), 28.6 % (8/28), and 53.6 % (15/28) reporting these ratings at Week 8. The sensitivity of effectiveness analyses was validated based on results using morphine SR; 98.0 % (49/50; 95 % CI, 89.35–99.95) of patients in the morphine SR group maintained pain control after 1 week of treatment. The overall safety profile was similar to that demonstrated in previous studies; tapentadol ER was associated with a lower incidence of gastrointestinal treatment-emergent adverse events than morphine SR [38.0 % (19/50) vs. 54.0 % (27/50)], including constipation [12.0 % (6/50) vs. 20.0 % (10/50)] and vomiting [6.0 % (3/50) vs. 26.0 % (13/50)].ConclusionsOverall, results indicate that conversion from previous strong opioids to tapentadol ER (50–250 mg twice daily) was successful and resulted in safe and effective pain control with improved gastrointestinal tolerability versus morphine SR in patients with moderate to severe cancer-related pain that was well-controlle...

Practical Considerations for the Use of Tapentadol Prolonged Release for the Management of Severe Chronic Pain

“…[36][37][38]42,45,56 The concomitant use of WHO step I analgesics and coanalgesics was permitted in the 4 previously described open-label, Phase IIIb studies of tapentadol PR in patients with low back pain with or without a neuropathic pain component 37,45 or with osteoarthritis knee pain. 38 42,85,86 tapentadol PR used concomitantly with morphine IR and oxycodone IR was well tolerated. Although only the concomitant use of morphine IR and oxycodone IR for breakthrough pain has been evaluated, these findings suggest that other IR opioids could be safely used as well.…”

Tapentadol for Cancer Pain Management: A Narrative Review

“…Nine studies were found with the aforementioned characteristics (4 randomized clinical trials and five nonrandomized, open‐label trials or clinical practice studies) (see Flow Diagram in Figure , Tables and ). Of the randomized trials, one of them is an open‐label, phase III study, conducted in Japan, to evaluate the efficacy and tolerability of conversion to oral tapentadol ER (50 to 250 mg twice daily) from previous around‐the‐clock strong opioids in subjects with moderate‐to‐severe, chronic cancer pain, with the aim of being able to recommend this change if necessary in clinical practice . A second study was a randomized, placebo‐controlled, double‐blind, phase 3 trial (NCT00472303), conducted in 16 countries, that aimed to evaluate the effectiveness and safety of tapentadol ER compared with placebo and morphine controlled release (CR) for managing moderate‐to‐severe chronic cancer pain .…”

Transmission pathways and mediators as the basis for clinical pharmacology of pain

“…Together, these studies suggest that dual opioid therapy may have advantages postoperatively in treating pain while reducing side effects [43]. Similarly, Tapentadol is a μ-opioid agonist and norepinephrine reuptake inhibitor that has been found to have fewer gastrointestinal effects, such as constipation and vomiting [44]. Imanaka et al [44] found that Tapentadol was able to induce pain control in 84% of patients with terminal cancer-related pain according to self-reported scores [44].…”

“…Similarly, Tapentadol is a μ-opioid agonist and norepinephrine reuptake inhibitor that has been found to have fewer gastrointestinal effects, such as constipation and vomiting [44]. Imanaka et al [44] found that Tapentadol was able to induce pain control in 84% of patients with terminal cancer-related pain according to self-reported scores [44]. The majority of the un-controlled patients did report some degree of improvement in their condition on Tapentadol [44].…”

“…Imanaka et al [44] found that Tapentadol was able to induce pain control in 84% of patients with terminal cancer-related pain according to self-reported scores [44]. The majority of the un-controlled patients did report some degree of improvement in their condition on Tapentadol [44]. Due to an improved side effect profile and good analgesic efficacy, it may be clinically appropriate to consider using Tapentadol before traditional opioid agonists whenever possible.…”