1. Tramadol/Paracetamol Fixed-dose Combination in the Treatment of Moderate to Severe Pain
Joseph V Pergolizzi Jr, Mart van de Laar, Richard Langford, Hans-Ulrich Mellinghoff, Ignacio Morón Merchante, Srinivas Nalamachu, Joanne O’Brien, Serge Perrot, Robert B Raffa
Journal of Pain Research
Powerpoint by Marvin Jino Bugna, MD

2. Introduction

3. Pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage.
Pain is not just a physical sensation.
It is influenced by attitudes, beliefs, personality and social factors, and can affect emotional and mental well-being.

4. 3 Main Categories of Pain
Acute pain lasts for a short time and occurs following surgery or trauma or other condition.
Chronic pain lasts beyond the time (more than 6 months) expected for healing following surgery, trauma or other condition.
Cancer pain can occur in patients with early stage and advanced disease, and in cancer survivors as a severe and debilitating side-effect of treatment.

5. Chronic Pain
Associated with surgery, trauma or other condition, or it can exist without a clear reason.
It can be a symptom of other disease, or it can be a stand-alone condition.
It might show up in a scan or test, or there may be no evidence of its existence.
It can occur anywhere in the body, or at multiple sites.
It can be daily, or recurrent.

6. Objectives

7. To be able to identify the different types of pain and its role in the body.
To determine the role and effectivity of fixed-dose combination of Tramadol and Paracetamol in managing moderate to severe pain.
To identify mitigating strategies that may be useful for patient’s pain management

8. Relevance

9. The fixed-dose combination of tramadol and paracetamol provides multimodal analgesia and good pain control in many patients with acute or chronic pain.
The combination has synergistic action so that the lower doses of single substances are needed to improves the pharmacological profile.
The combination results to an analgesic with a low potential for abuse and dependence. This makes possible the use of the medication without restrictive prescribing regimen and makes it more accessible to patients for the relief of moderate to severe pain.

10. Highlights

11. Weighing the Risks of Treatment with High-dose NSAIDs and Paracetamol
Paracetamol or acetaminophen is frequently grouped with NSAIDs, but it is actually an aniline analgesic.
NSAIDs (Non-steroidal anti-inflammatory drugs) use has been associated with bronchospasm.
Short term use of NSAIDs was associated with increased risk of death in patients with a history of myocardial infarction.

12. Weighing the Risks of Treatment with High-dose NSAIDs and Paracetamol
NSAIDs, including coxibs, should not be prescribed as a panacea for all pains, but restricted to pain related to tissue damage and/or inflammation, in accordance to their mechanism of action.
NSAIDs are to be used cautiously, in patients with or at elevated risk for cardiovascular disease or gastrointestinal complications.

13. Mitigation Strategies that may be Useful for Patients Receiving Paracetamol or NSAIDs for Pain Management

14. Tramadol and Paracetamol
Paracetamol is the analgesic of choice for mild to moderate pain and to reduce fever.
Tramadol is an opioid analgesic, effective in relieving pain that does not respond to paracetamol. It should be used with caution in those patients with a history of alcohol or drug abuse as some risk of dependency does exist.

15. Why Combinations Might be Better than Single Agents?
Combination analgesics might reduce adverse events.
Combining two or more agents may result in an additive or synergistic analgesic effect.
Complementary pharmacokinetics of tramadol/paracetamol in combination enhance the probability of effective pain relief

16. Fixed-dose Combination of Tramadol/Paracetamol
Paracetamol blocks the production of chemicals in the body that are responsible for pain and fever, while tramadol exerts its effect by acting on parts of the central nervous system which process pain signals.

17. Potential Advantages of a Fixed-dose Tramadol/Paracetamol Analgesic Product Include:
Broader analgesic spectrum
Complementary pharmacokinetic profile
Potentially synergistic analgesic effect
Greater convenience (possibly resulting in better compliance, thus, improved therapy)
Improved ratio of efficacy to adverse effects.

18. Strengths And Weakness of Tramadol/Paracetamol and NSAIDs

19. Conclusion

20. Tramadol and Paracetamol in fixed-dose combination provide good pain control in many patients with acute or chronic pain.
Its combination produces a better analgesic effect, which is reached with lower doses of the single substances, compared to that of equal doses used in single treatment.

21. The fixed-dose combination of tramadol and paracetamol is an analgesic with a low potential for abuse and dependence.
It is not limited by a restrictive prescribing regimen, which makes it more accessible to patients for the relief of moderate to severe pain.
However, further studies are warranted to establish the long-term efficacy and safety of these products.

22. References
World Health Organization (WHO). WHO’s pain ladder [web page on the Internet]. Geneva: WHO; Available from: Accessed May 12, 2011.
Varrassi G, Müller-Schwefe G, Pergolizzi J, et al. Pharmacological treatment of chronic pain – the need for CHANGE. Curr Med Res Opin. 2010;26(5):1231–1245.