Overall Safety Profile and Effectiveness of Tramadol hydrochloride/acetaminophen in Patients With Chronic Noncancer Pain in Japanese Real-World Practice

Curr Med Res Opin. 2015 Nov;31(11):2119-29. doi: 10.1185/03007995.2015.1091975. Epub 2015 Sep 28.


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 = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 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 -2.7 (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.

Trial registration: This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).

Keywords: Acetaminophen; Adverse drug reactions; Effectiveness; Naturalistic practice; Pain, Chronic; Tramadol hydrochloride.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage*
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Opioid / administration & dosage*
  • Chronic Pain / drug therapy*
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Pain Measurement
  • Prospective Studies
  • Tablets
  • Tramadol / administration & dosage*
  • Treatment Outcome
  • Young Adult


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Tablets
  • Acetaminophen
  • Tramadol