Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice

Abstract

Objective: To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. Research design and methods:This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. Results:A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n ¼ 87 [6.9%]), constipation (n ¼ 63 [5.0%]), dizziness and somnolence (n ¼ 29 [2.3%] each), and vomiting (n ¼ 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by À2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. Conclusion:This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs.

Use of Fentanyl Patch for Treatment of Moderate‐to‐severe Chronic Noncancer Pain: Postmarketing Surveillance of Medical Practice in Japan Using a Risk Minimization Action Plan

“…The discontinued rate of FP therapy was 48.5% ( n = 242) during the entire observation period. This rate was fairly consistent with previous studies that also evaluated safety and effectiveness of opioids on managing chronic pain using a similar study design …”

“…This rate was fairly consistent with previous studies that also evaluated safety and effectiveness of opioids on managing chronic pain using a similar study design. 13,14 The ADR incidence was the highest during the period after baseline and before Day 30 (38%), which rapidly decreased to 10.8% during the subsequent 30-day period and to approximately 10% thereafter. These results are consistent with the following data from previous studies: The incidence of ADRs was 67.2% during the period from Day 1 to Day 8, but <10% during the period from Day 9 to Day 22, and 35.3% (approximately 30% each for gastrointestinal disorders and constipation) during the period from Day 23 to Day 29 in the 4-week clinical registration trial in Japan.…”

Impact of nonsteroidal anti-inflammatory drug administration for 12 months on renal function

“…TA combination tablets, which combine tramadol hydrochloride and acetaminophen, are a widely used analgesic [22]. Tramadol is a synthetic opioid receptor agonist with analgesic properties that also has a unique monoaminergic action through serotonin-noradrenaline reuptake inhibition [23].…”

“…Acetaminophen is one of the more traditional and better-tolerated among fast-acting analgesics that block pain through different pathways than opioids [24]. The effectiveness of TA in the treatment of chronic non-cancer pain is clinically acceptable, and improvements in pain contribute to improvements in quality of life in practice [15].…”

“…Change of administration dose was permitted. The initial dosage and administration of TA was one tablet (tramadol hydrochloride 37.5 mg and acetaminophen 325 mg) given orally four times per day [15]. The dose could be increased or decreased depending on patients' symptoms, but no more than two tablets per administration was permitted (up to a maximum of eight tablets daily).…”