Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia—Approved Products and Challenges

Abstract

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute painful conditions like post-operative and post-traumatic pain. Despite the satisfactory results achieved by oral analgesics, parenteral analgesia remains a key tool in the treatment of painful conditions when the enteral routes of administration are inconvenient. Parenteral ready-to-use fixed-dose combinations of non-opioid analgesics combinations, including NSAIDs and paracetamol or metamizole, could play a central role in the treatment of painful conditions by combining the advantages of multimodal and parenteral analgesia in a single formulation. Surprisingly, only in 2020, a parenteral ready-to-use fixed-dose combination of ibuprofen/paracetamol was launched to the market. This review aims to investigate the current availability of combinations of NSAIDs with paracetamol or metamizole in both European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, we explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. We concluded that, despite the well-recognized utility of combining NSAIDs with paracetamol or metamizole, several randomized clinical trial studies demonstrate no clear advantages concerning their efficacy and safety. Future clinical trials specifically designed to assess the efficacy and safety of pre-formulated fixed-dose combinations are required to generate solid evidence about their clinical advantages.

Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial

“…Multimodal analgesia protocol is necessary to relieve postoperative pain and reduce postoperative complications [ 19 ]. Multimodal analgesia involves different anesthesia techniques and a combination of various analgesics medications targeting multiple receptors within nociceptive and neuropathic pathways to prevent and manage pain [ 20 ]. In this study, patients undergoing thoracoscopic surgery were intravenously treated with paracetamol and mannitol injection during and after surgery, combined with TPVB, to reduce opioid consumption and alleviate acute pain.…”

The Adequacy of Anesthesia Guidance for Vitreoretinal Surgeries with Preemptive Paracetamol/Metamizole

“…Metamizole and paracetamol (acetaminophen) are the two most widely used non-opioid analgesics, possessing both a central (inhibition of cyclooxygenase-3, COX-3) and a peripheral mechanism of action [ 8 , 9 , 10 , 11 , 12 ], which have proven their analgesic efficacy in the treatment of postoperative pain with a single dose administered as preemptive analgesia [ 13 , 14 , 15 , 16 , 17 , 18 ], in reducing the incidence of PONV [ 13 , 14 ] and a quite good safety profile [ 11 , 19 , 20 , 21 ] compared to standard nonsteroidal anti-inflammatory drugs (NSAIDs), in terms of safety for the upper intestinal tract and kidneys in patients with an increased risk of stomach or renal problems or other contraindications for standard NSAIDs [ 22 , 23 ].…”

Charting the Knowledge and Patterns of Non-steroidal Anti-inflammatory Drugs Usage in Hail Population, Saudi Arabia: Insights into the Adverse Effect Profile

“…Nonsteroidal anti-inflammatory drugs (NSAIDs) are a widely recognized group of medicines that possess fever-reducing, pain-relieving, and anti-inflammatory properties [1]. From the ancient utilization of willow leaves containing salicylates to the more recent fluctuations in the popularity of highly selective cyclooxygenase-2 (COX-2) inhibitors and the emergence of the latest dual-acting anti-inflammatory compounds, there has been a continuous and dynamic evolution in this field [2].…”