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

Abstract

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.

Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study – PRIME study

“…No serious adverse reaction was reported in the study. NSAIDs are commonly associated with GI adverse effects 20. In our study, five patients reported nine events related to GI tract.…”

Tramadol hydrochloride: Pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems

“…The inhibition of 5-HT and NE reuptake may account for 213 triggering two significant adverse events: seizures and serotonin 214 syndrome, particularly likely in patients receiving the drug in 215 overdose, or when co-administered with antidepressants or even 216 at the recommended dose in patients with history of epilepsy 217 [17, 26,27]. 218 Some authors hypothesized the mechanism of TrHC-induced 219 seizures.…”

“…opioids are combined with non-opioid analgesic drugs that act via 289 different mechanisms and provide an additive or synergistic effect 290 [27]. For instance, clonidine and other a2-adrenergic agonists are 291 commonly used for this purpose.…”

Evaluation of Use of Analgesics in Pain Management Among Surgeons in a Tertiary Care Hospital

“…Tramadol with acetaminophen combination provides the potential benefits by increasing efficacy and reducing the adverse effects. Both the component have a different mechanism of action and the combination shows a synergistic effect in pain relief [18]. The goal of the therapy is to facilitate patient compliance, simplify prescribing and improve efficacy without increasing adverse effects and is achieved with combination therapy [19].…”