Pain and Therapy (Sep 2024)

Safety of Co-Crystal of Tramadol-Celecoxib (CTC) in Patients with Acute Moderate-to-Severe Pain: Pooled Analysis of Three Phase 3 Randomized Trials

  • Eugene R. Viscusi,
  • Richard Langford,
  • Adelaida Morte,
  • Anna Vaqué,
  • Jesús Cebrecos,
  • Mariano Sust,
  • José María Giménez-Arnau,
  • Oscar de Leon-Casasola

DOI
https://doi.org/10.1007/s40122-024-00655-w
Journal volume & issue
Vol. 13, no. 6
pp. 1617 – 1631

Abstract

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Abstract Introduction Multi-modal analgesia is desirable for the management of acute pain since it can provide effective pain relief at lower doses, thereby aiding tolerability. Co-crystal of tramadol-celecoxib (CTC) provides effective analgesia in models of acute pain. Co-crystallization can alter the pharmacokinetics of individual components, potentially improving tolerability. We sought to better understand the safety and tolerability of CTC in patients with acute postoperative pain. Methods We conducted a pooled analysis of safety data from three phase 3 randomized controlled trials in adults with acute moderate-to-severe pain following oral surgery, bunionectomy, and elective abdominal hysterectomy. We present data for CTC 200 mg twice daily (BID) and its comparators: tramadol 50 mg four times daily (QID) (one trial), tramadol 100 mg QID (two trials), celecoxib 100 mg BID (two trials), and placebo (three trials). Results In total, n = 551 patients received CTC 200 mg BID, n = 183 received tramadol 50 mg QID, n = 368 received tramadol 100 mg QID, n = 388 received celecoxib 100 mg BID, and n = 274 received placebo. The prevalence of adverse events (AEs) related to study drug up to 48 h was numerically lower with CTC 200 mg BID (35.9%) than with tramadol 50 mg QID (47.5%) and 100 mg QID (44.8%) but greater than with celecoxib 100 mg BID (12.4%) and placebo (20.4%). The most frequent AEs related to study drug up to 48 h were somnolence, nausea, dizziness, and vomiting, which occurred more frequently in patients receiving tramadol 100 mg QID than in those receiving CTC 200 mg BID. Conclusion CTC 200 mg BID appears to be better tolerated than tramadol 100 mg QID, possibly because of reduced total exposure to tramadol. This may contribute to a more favorable benefit-risk profile for CTC versus individual components, making it a promising treatment for acute pain. Trial Registration ClinicalTrials.gov identifiers: NCT03108482, NCT02982161 (EudraCT: 2016-000592-24), NCT03062644 (EudraCT: 2016-000593-38).

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