Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

Abstract

Joseph V Pergolizzi Jr,1,2 Mart van de Laar,3 Richard Langford,4 Hans-Ulrich Mellinghoff,5 Ignacio Morón Merchante,6 Srinivas Nalamachu,7,8 Joanne O'Brien,9 Serge Perrot,10 Robert B Raffa111Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; 2Association of Chronic Pain Patients, Houston, TX, USA; 3Arthritis Center Twente (MST and UT), Enschede, The Netherlands; 4Anaesthetics Laboratory, St Bartholomew's Hospital, London, UK; 5Department of Endocrinology, Diabetology and Osteology, Kantonsspital St Gallen, St Gallen, Switzerland; 6Centro de Salud Universitario Goya, Madrid, Spain; 7Kansas University Medical Center, Kansas City, KS, USA; 8International Clinic Research, Leawood, KS, USA; 9Department of Pain Management, Beaumont Hospital, Beaumont, Dublin, Ireland; 10Service de Médecine Interne et Consultation de la Douleur, Hôpital Dieu, Paris, France; 11Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USAAbstract: Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a "do ask, do tell" approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicity.Keywords: NSAIDs, opioids, combination analgesics, moderate pain, severe pain, analgesics, tramadol/paracetamol