ArticlePain and therapy2025
Adverse Reactions Following First-Dose Administration of Co-Crystal of Tramadol-Celecoxib Versus Tramadol Alone for Moderate-To-Severe Acute Pain.
Article in Pain and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03108482 (A Randomized, Double-blind, Active-), which is not on this map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Active- (Tramadol and Celecoxib) and Placebo-controlled, Parallel Groups, Phase 3 Clinical Trial to Establish the Efficacy of Co-crystal E-58425 for the Management of Moderate to Severe Post-surgical Pain After Bunionectomy.
Who cites it
1 citing paper in PubMed.
- Review of Structural Modification and Development of Novel Tramadol Derivatives.Molecules (Basel, Switzerland) · 2026Review
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPhase 3 clinical trials in moderate-to-severe acute pain have shown that co-crystal of tramadol-celecoxib (CTC) has improved efficacy and comparable tolerability versus immediate-release tramadol 50 mg alone, with a similar tramadol daily dose, over a 48-h treatment period. However, it is not known how first-dose tolerability compares, given that the administered dose of tramadol is higher in CTC 200 mg (88 mg) versus immediate-release tramadol 50 mg. This was explored in a post hoc analysis of a pivotal phase 3 trial.
methodsA randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial was conducted in patients with moderate-to-severe acute postoperative pain (NCT03108482) and has been previously reported. This post hoc analysis evaluated the prevalence of the four most common study drug-related, opioid-associated, treatment-emergent adverse reactions reported in phase 3 CTC clinical trials: somnolence, nausea, dizziness, and vomiting. Prevalence was evaluated in 2-h intervals, up to 6 h post first dose (just before second-dose administration) of CTC 200 mg or immediate-release tramadol 50 mg p.o. Descriptive analysis was performed.
resultsEach group comprised 183 participants for analysis. The proportions of patients reporting drug-related, treatment-emergent adverse reactions of somnolence, nausea, dizziness, and vomiting were similar between treatment groups at 2, 4, and 6 h following the first dose.
conclusionsThis post hoc analysis indicates that the higher dose of tramadol (88 mg) given in CTC 200 mg did not result in an increase in drug-related adverse reactions after first-dose administration, and had a similar tolerability profile, compared with immediate-release tramadol 50 mg alone (the lowest dose recommended for the management of moderate-to-severe acute pain). This is in line with earlier findings for the 48-h treatment period of this phase 3 trial and may be explained by CTC's differentiated physiochemical properties related to its co-crystal structure. These findings may have utility for practicing clinicians.
trial registrationClinicalTrials.gov identifier, NCT03108482.
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