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

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.