| Drug Name: | Tapentadol / Aspadol |
| Dosage: | 50 – 220 mg |
| Packages: | 30 – 360 pills |
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| Shipment: | US2US EU2EU int. |
| Order Tapentadol: | Visit DrugStore |
Tapentadol has been in clinical use for more than 12 years across Australia, Europe, and the United States, and its role in pain management continues to expand. It was developed through rational drug design to combine two complementary mechanisms: μ-opioid receptor (MOR) agonism and norepinephrine reuptake inhibition (NRI). Tapentadol remains the first and only available agent within this MOR-NRI class.
Unlike traditional opioids such as morphine, fentanyl, or oxycodone, which act solely via MOR activation, tapentadol delivers analgesia through a dual mechanism. By both stimulating MOR and blocking norepinephrine reuptake, it suppresses pain transmission through ascending and descending pathways. MOR activation is key for reducing acute nociceptive pain, while the NRI component helps limit central sensitization and lowers the risk of progression from acute to chronic neuropathic pain.
Tapentadol also differs from tramadol, as it does not have clinically relevant serotonergic activity, making its analgesic effects more predictable across various clinical scenarios. It is available in immediate-release and prolonged-release (PR) formulations. Its potency is approximately two to three times higher than tramadol, though less than that of morphine or oxycodone. Because it is metabolized mainly via hepatic glucuronidation rather than cytochrome P450 pathways, tapentadol shows fewer drug–drug interactions and reduced variability related to genetic polymorphisms.
Although tapentadol binds to MOR with lower affinity compared to morphine, its combined MOR and NRI actions provide effective pain relief. This dual activity also results in a reduced “μ-load,” meaning fewer opioid-related side effects such as constipation, respiratory depression, or endocrine disturbances compared with pure MOR agonists.
Cancer-related pain is highly prevalent, affecting more than 60% of patients with advanced disease. Tapentadol has been studied in diverse oncology populations, including opioid-naïve patients, those pretreated with opioids, and individuals with nociceptive, neuropathic, or mixed pain linked to solid tumors, hematologic malignancies, or anticancer therapies.
To date, at least five randomized phase III trials and multiple nonrandomized studies have investigated tapentadol in cancer pain. Collectively, these studies confirm its efficacy and favorable tolerability, supporting tapentadol as a valuable therapeutic option for the management of cancer-related pain.
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Five randomized controlled phase III trials and several nonrandomized studies have examined tapentadol in patients with cancer pain. The randomized trials form the core evidence, supplemented by recent observational data and long-term findings from noncancer pain populations.
Earlier systematic reviews, including a Cochrane analysis, identified four RCTs with over 1,000 adults experiencing moderate to severe cancer pain. These trials compared tapentadol with morphine, oxycodone, and placebo. A more recent RCT involving 114 patients tested tapentadol alone versus tapentadol plus duloxetine in chemotherapy-induced peripheral neuropathy (CIPN). Because of methodological differences, pooling of data was not possible. Most studies were considered low or uncertain risk of bias, although one was open-label and another stopped early, leaving it underpowered. With the exception of the most recent unfunded study, all were industry-sponsored.
Overall, the trials showed that tapentadol provided pain relief comparable to morphine and oxycodone. Most were noninferiority in design, and across studies, tapentadol demonstrated a similar safety profile with less constipation than other opioids.
Two pivotal multicenter, double-blind, active-controlled phase III trials investigated prolonged-release (PR) tapentadol. The Asian study demonstrated that tapentadol PR was at least as effective as oxycodone PR in reducing pain, while significantly lowering rates of constipation. The European trial confirmed tapentadol’s superiority over placebo and its noninferior efficacy compared with morphine PR, with better gastrointestinal tolerability. A post-hoc subgroup analysis showed that patients dissatisfied with tramadol could be safely converted to tapentadol, with 70% achieving pain reduction.
An additional Japanese open-label trial with 100 patients further supported tapentadol’s effectiveness, demonstrating successful conversion from strong opioids and improved gastrointestinal tolerability relative to morphine. The most recent RCT in 114 patients with CIPN compared tapentadol alone with tapentadol plus duloxetine. Both groups experienced significant reductions in pain and quality-of-life improvements, with no differences in safety outcomes, confirming the noninferiority of tapentadol monotherapy.
Taken together, five phase III RCTs confirm that tapentadol is at least as effective as morphine and oxycodone, superior to placebo, and better tolerated with fewer gastrointestinal adverse effects.
Beyond RCTs, nonrandomized evidence supports these findings. A large prospective multicenter trial in Korea enrolled 650 patients, including 349 with chronic cancer pain. Tapentadol reduced pain intensity by an average of 2.1 points on the 11-point NRS within four weeks, with sustained benefit over six months. More than 90% of patients reported meaningful improvement, further reinforcing the drug’s clinical value.
A small prospective open-label Italian study investigated tapentadol in 31 patients with chemotherapy-induced peripheral neuropathy (CIPN). Within the first week, seven patients (23%) discontinued due to mild adverse events, and one withdrew. After three months, 19 of 22 patients (86%) who continued treatment experienced significant pain relief, with 68% reporting at least a 50% reduction in pain. Tapentadol also significantly lowered NRS and DN4 scores (P < 0.001) and improved global health status (P = 0.046).
A retrospective comparative study in Japan evaluated 127 cancer patients with neuropathic pain who received tapentadol, methadone, oxycodone, fentanyl, or hydromorphone. Tapentadol achieved significantly greater pain reduction compared with oxycodone at all measured timepoints (day 7, P = 0.0024), and showed a nonsignificant trend toward superiority over methadone, fentanyl, and hydromorphone. Discontinuation rates were lowest with tapentadol (0%) compared with other opioids (3.8–10%).
Another single-center retrospective Japanese study of 84 patients with moderate to severe cancer pain found that 93% achieved ≥50% reduction in NRS scores. Median pain intensity dropped from 7 at baseline to 2 after initial response, and to 1 at the end of the maintenance period (P < 0.0001). Pain relief was seen in both opioid-naïve and opioid-tolerant patients, typically within three days. Nausea resolved in nearly half of affected patients, and no serious adverse-event-related discontinuations were reported.
In a larger multicenter retrospective study of 906 Japanese cancer patients, 17% discontinued tapentadol because of adverse events, most frequently nausea (5%), drowsiness (2%), delirium, or cardiovascular symptoms (1%). The majority of discontinuations occurred within the first month of treatment. Another single-center study involving 175 patients noted that tapentadol was most often initiated by palliative care teams, particularly in patients with neuropathic pain or a history of nausea; 8% discontinued due to adverse effects.
Overall, recent prospective and retrospective studies indicate that tapentadol is a safe and effective option for managing cancer pain, though the uncontrolled design of many of these studies requires cautious interpretation.
Chronic noncancer pain
Systematic reviews and observational data also confirm tapentadol’s role beyond oncology. Evidence supports its effectiveness in diabetic peripheral neuropathy and chronic low back pain. A network meta-analysis demonstrated lower rates of nausea and constipation compared with other strong opioids. In a Spanish multicenter, open-label 72-week extension study, 81 patients with severe osteoarthritis or low back pain maintained stable pain control and quality of life improvements, with high treatment satisfaction. Adverse events occurred in 18%, most commonly constipation (7%).
Additional observational studies comparing tapentadol with opioids such as fentanyl, morphine, buprenorphine, and oxycodone consistently showed superior pain relief and tolerability for tapentadol. A German 12-week database study of 2,331 patients with chronic low back pain reported higher responder rates and better safety with prolonged-release tapentadol (P < 0.001).
Conclusion
Tapentadol, with its combined MOR agonist and NRI activity, has been extensively evaluated in both cancer and noncancer pain populations. Phase III randomized trials confirm its noninferior efficacy compared with morphine and oxycodone, with fewer gastrointestinal side effects. Nonrandomized studies further support its effectiveness and tolerability, while long-term data suggest sustained pain relief for up to two years without evidence of tolerance. Tapentadol represents a valuable alternative to morphine or oxycodone, especially for patients with gastrointestinal intolerance or when long-term analgesic therapy is required.
