rofecoxib (TRM-201) / Tremeau Pharma - LARVOL DELTA

Anilino-1,4-naphthoquinone derivatives exhibit antiproliferative, anti-inflammatory, and pro-apoptotic activities in LPS-stimulated SW480 colorectal cancer cells: In vitro and in silico studies. (PubMed, Biomed Pharmacother) - "Through integrated computational and experimental approaches, we demonstrated that three compounds bind favorably within the COX-2 active site with key residues in a manner comparable to that of rofecoxib...The compounds were also associated with mitochondrial dysfunction, cell cycle changes, and apoptosis, with compound 12 emerging as the most active derivative and showing the strongest antiproliferative and pro-apoptotic effects. Our findings establish compound 12 as a promising lead candidate for the development of new anti-colorectal cancer agents and provide mechanistic insights into the interplay between COX-2 inhibition, inflammatory modulation, and apoptosis induction in inflammation-associated colorectal carcinogenesis."

Journal • Preclinical • Colorectal Cancer • Metabolic Disorders • Oncology • Solid Tumor • CXCL8 • IL10 • TNFA

Selective COX-2 inhibitors for short-term musculoskeletal pain in inflammatory bowel disease in remission: a narrative review. (PubMed, BMJ Open Gastroenterol) - "Clinical trials and clinical studies evaluating celecoxib, etoricoxib or rofecoxib in patients with IBD and musculoskeletal/rheumatological symptoms were considered when gastrointestinal (GI) outcomes were reported. Overall, the strongest available evidence supports cautious short-term use of selective COX-2 inhibitors in selected patients with IBD in remission when anti-inflammatory analgesia is required. Given the small evidence base and limited follow-up, treatment should be time-limited, use the lowest effective dose and include clinical monitoring."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Rheumatology • Ulcerative Colitis

Causal association and molecular mechanisms of periodontal disease and muscle wasting and atrophy: Mendelian randomization and bioinformatics analysis. (PubMed, Front Genet) - "These are only the results of the preliminary virtual screening, including rofecoxib, TT-301 and nelfinavir. This relationship is mediated by chronic inflammation centered on IL-6, IL-1β, and IL-10 within the PI3K-Akt pathway. The findings provide a translational foundation for dual-targeting therapeutic strategies."

Journal • Dental Disorders • Inflammation • Muscular Atrophy • Periodontitis • IL10 • IL1B • IL6

Identification of drug-related cardiovascular risks: A comprehensive analysis using the FAERS database (2004-2024). (PubMed, PLoS One) - "This study showed that some drugs were significantly associated with CVD, and some of them were newly discovered signals. These findings provide a basis for the generation of new hypotheses about the cardiovascular risk of drugs, but the causal relationship needs to be confirmed by further research."

Journal • Retrospective data • Cardiovascular • Oncology

Efficacy of tenoxicam for postoperative dental pain: a systematic review of randomized controlled trials. (PubMed, J Dent Anesth Pain Med) - "Comparators included placebo, ibuprofen, diclofenac, flurbiprofen, meloxicam, methylprednisolone, and rofecoxib. Tenoxicam appears to be an effective and well-tolerated option for postoperative dental pain management. Study heterogeneity and domain-level bias concerns indicate a need for additional high-quality trials to confirm these findings and support routine clinical use."

Journal • Review • Pain

Assessing safety trends of withdrawn medications: A data-driven pharmacovigilance approach using growth models. (PubMed, Explor Res Clin Soc Pharm) - "For comparative safety assessment, 15 commonly used cancer medications (including Tamoxifen, Avastin, Bleomycin, Paclitaxel, Vincristine, Methotrexate, Cisplatin, Doxorubicin, Imatinib, Docetaxel, Rituximab, Trastuzumab, Revlimid, Lenalidomide, and Pembrolizumab) were analyzed...The examples presented in this investigation demonstrated that the drugs Benoxaprofen, Rosiglitazone, Temazepam, and Rofecoxib exhibited a robust correspondence with diverse modeling approaches...It also provides a foundation for future research. This research could help support safer clinical decisions and regulatory evaluations for both pharmaceuticals that are no longer on the market and those that are still available."

Adverse events • Journal • Oncology

CARDIORENAL SAFETY OF NSAIDS IN PATIENTS WITH ARTHRITIS: A NETWORK METANALYSIS (ACC 2026) - " We included 23 studies (19 RCTs, 4 cohort) with 1245,108 patients,NSAIDs evaluated were Naproxen (n=69,209),Ibuprofen(n=535,651), Celecoxib(n=107,493),oral Diclofenac (n=335,154),Rofecoxib (n=105,102), Nabumetone (n=507),Valdecoxib (n=5,075), Meloxicam (n=27,713),Piroxicam (n=14,585),Mefenamic acid (n=13,856),Indomethacin (n=26,254),placebo (n=4192), Acetaminophen (n=287),and Amtolmetin guacil (n=30).Compared to placebo, Valdecoxib had highest odds of MACE [OR: 2.96 (95%CI:1.80-4.85)] and Rofecoxib highest odds of renal AEs [OR: 5.11 (95%CI: 2.58-10.10)].League tables showed no differences between different NSAIDs, SUCRA rankings identified Celecoxib with highest MACE and Rofecoxib with highest renal risk (Figure). Valdecoxib and Rofecoxib confer the highest cardiorenal risks. SUCRA rankings ranked Celecoxib as highest for MACE risk and Rofecoxib for renal risk, underscoring the importance of NSAID-specific safety profiles to guide arthritis treatment decisions."

Clinical • Cardiovascular • Immunology • Rheumatology

Risk factors for drug-related ischemic stroke: an analysis of the FDA adverse event reporting system (FAERS). (PubMed, J Clin Neurosci) - "This large-scale FAERS analysis systematically characterized drug-IS associations, identifying multiple strong and independent pharmacological risk signals and revealing temporal patterns. The findings provide real-world evidence to guide clinical decision-making and targeted pharmacovigilance."

Adverse events • Journal • Cardiovascular • Ischemic stroke • Oncology

Real-World Pharmacovigilance Analysis of Drug-Induced Decreased Cardiac Ejection Function: Evidence from the FAERS Database (2004-2024). (PubMed, Curr Cardiol Rev) - "This large-scale real-world analysis identifies both established and novel DCEF risk signals, highlights heterogeneity in onset timing, and emphasizes the predominance of antineoplastic agents. Clinically, these findings suggest the need for periodic echocardiographic monitoring of left ventricular ejection fraction, particularly in patients receiving high-risk drugs such as mitoxantrone, trastuzumab, doxorubicin, and pertuzumab. Early-phase monitoring is crucial for "early-failure" agents, while extended follow-up is warranted for drugs with delayed toxicity, such as doxorubicin. These results provide actionable evidence to support individualized risk management and regulatory label updates."

Adverse events • Journal • Real-world evidence • Cardiovascular • Oncology

Early Identification of Cardiovascular Adverse Events Associated With Rofecoxib Using Real-World Data From the UK: A Nested Case-Control and Case-Crossover Study. (PubMed, Pharmacoepidemiol Drug Saf) - "Using RWD, cardiovascular adverse effects of rofecoxib could have been detected within 2 years of the market entry in the UK, well before traditional pharmacovigilance methods. This supports incorporating RWD analysis into routine drug safety monitoring."

Adverse events • Journal • Real-world evidence • Cardiovascular

Drug related lipid metabolism abnormalities: a real-world pharmacovigilance exploratory analysis based on U.S. FDA adverse event reporting system (FAERS) (PubMed, Nutr Hosp) - "this study reveals the increasing prevalence of drug-induced lipid metabolism disorders and underscores the need for enhanced monitoring and timely updates to drug labels for high-risk medications. By leveraging real-world data and advanced signal detection methods, this research provides a robust framework for identifying emerging risks, contributing uniquely to public health and regulatory science."

Adverse events • Journal • Real-world evidence • Dyslipidemia • Metabolic Disorders

Retrieval Augmented Generation (RAG) for Evaluating Regulatory Compliance of Drug Information and Clinical Trial Protocols. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The drug information for adalimumab, insulin glargine, atorvastatin calcium, sertraline, and alprazolam was evaluated for compliance with Food and Drug Administration (FDA) clinical pharmacology guidance for indications, use in specific populations, and warnings and precautions. The reasons for the withdrawal of rofecoxib, valdecoxib, and troglitazone were elicited. The clinical trial protocol evaluation system was used to assess a Phase-2a clinical trial protocol of Rifafour in tuberculosis with the FDA E9 and E9 (R1) guidance documents...The findings aligned with manual protocol reviews. RAG-based AI methods can improve the usefulness of LLMs in document-restricted settings and are a promising approach for evaluating the compliance of clinical pharmacology documents."

Compliance • Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Evaluating adverse events reported for non-steroidal anti-inflammatory drugs in osteoarthritis: a real-world pharmacovigilance study. (PubMed, Inflammopharmacology) - "This study complementing evidence from clinical trials and epidemiological research, by detecting potential adverse reaction signals not fully captured or reflected in approved product information, thus providing a pharmacovigilance perspective grounded in real-world data."

Adverse events • Journal • Real-world evidence • Cardiovascular • CNS Disorders • Depression • Dermatology • Dyspepsia • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Ischemic stroke • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Pain • Peptic Ulcer • Psychiatry • Respiratory Diseases • Rheumatology • Vascular Neurology

COL14A1 drives ischemic cardiac injury in PCOS: an artificial intelligence-identified biomarker. (PubMed, QJM) - "COL14A1 may represent a shared molecular link between PCOS and increased susceptibility to ischemic cardiac injury, potentially acting through macrophage-associated immune activation and fibroblast-mediated ECM remodelling. Rofecoxib may serve as a potential repurposed therapeutic candidate pending further validation. These findings provide mechanistic insights into the ovario-cardiac axis and highlight COL14A1 as a promising target for future risk stratification and intervention studies in women with PCOS."

Biomarker • Journal • Cardiomyopathy • Cardiovascular • Inflammation • Polycystic Ovary Syndrome • COL14A1 • TPM2

Drug-associated deep vein thrombosis: a disproportionality analysis of the FDA adverse event reporting system (FAERS) database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The ten highest-ranking agents by case count were drospirenone/ethinyl estradiol (ROR 69.09), ethinyl estradiol/etonogestrel (ROR 43.41), lenalidomide (ROR 4.89), testosterone (ROR 30.13), rofecoxib (ROR 5.41), ethinyl estradiol/norelgestromin (ROR 28.53), bevacizumab (ROR 3.53), thalidomide (ROR 9.26), pomalidomide (ROR 3.18), and celecoxib (ROR 3.90). This large-scale pharmacovigilance analysis identifies robust DVT signals across multiple drug classes, notably hormonal therapies, immunomodulators, and targeted anticancer agents. The results highlight the importance of proactive thrombotic risk assessment and monitoring in clinical practice when using these medications."

Adverse events • Journal • Cardiovascular • Hematological Disorders • Oncology • Thrombosis • Venous Thromboembolism

Cyclooxygenase-2 selective inhibitors increase the risk of alveolar osteitis: A systematic review and meta-analysis. (PubMed, Med Oral Patol Oral Cir Bucal) - "Data indicates that rofecoxib increases the risk of alveolar osteitis in patients undergoing tooth extraction."

Journal • Retrospective data • Pain

Reformulating Rofecoxib: Targeted Nanostructured Lipid Carrier Gel for Localized Treatment of Rheumatoid Arthritis. (PubMed, Drug Dev Ind Pharm) - "In vivo, ROX-NLC gel significantly reduced paw swelling and arthritis scores, preserved joint architecture, and avoided cardiac alterations observed with oral ROX. Biodistribution confirmed negligible systemic drug levels (below LOD: 0.079 µg/mL). ROX-NLCs gel provides a safe, sustained, and effective topical delivery system for RA therapy, enhancing local efficacy while reducing systemic cardiotoxic risk."

Journal • Cardiovascular • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Rofecoxib-Derived Theranostic Probe and Its Combination With PD-1 Inhibitor for High-Efficiency Cancer Therapy. (PubMed, Arch Pharm (Weinheim)) - "Compound 2 involves activating fluorescence by targeting tumor markers COX-2 as well as enhancing therapeutic efficacy. We believe this approach could provide insights for advancing cancer diagnosis and treatment technologies."

IO biomarker • Journal • Oncology • PD-L1

From chronic gastritis to gastric cancer: Mendelian randomisation and multi-omics interrogation of leukaemia inhibitory factor receptor (LIFR), hepatocyte growth factor (HGF), serine protease inhibitor E1 (SERPINE1) and interleukin-10 receptor subunit beta (IL10RB). (PubMed, Int J Biol Macromol) - "Collectively, these data define a molecular continuum from chronic gastritis to GC and highlight LIFR, IL10RB, SERPINE1 and HGF as pivotal biological macromolecules and candidate therapeutic targets. The repurposing potential of anti-inflammatory agents, particularly rofecoxib and nabumetone, suggests a feasible strategy to intercept the gastritis-carcinoma sequence."

Journal • Gastric Cancer • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • IL10 • LIFR • SERPINE1

Drug exposure before and during pregnancy and thromboembolic events: a disproportionality analysis from the FAERS database. (PubMed, Int J Surg) - "Drawing on the FAERS database, we have provided a list of drugs with risk signals for PTEs in this exploratory study. Our findings highlight the importance of considering both before and during-pregnancy drug exposures when assessing thromboembolism risk. More well-designed studies are warranted for drugs whose association with PTEs is not fully understood."

Journal • Cardiovascular

Synthesis, structural elucidation, and molecular docking of diclofenac-derived hydrazone metal complexes with anti-inflammatory and anticancer potential. (PubMed, Sci Rep) - "The HDN ligand exhibited potent COX-2 inhibition (IC₅₀ = 0.06 µM) with a selectivity index (SI) of 174.5, outperforming diclofenac sodium (SI = 4.52) and indomethacin (SI = 1.25), and approaching rofecoxib (SI = 725). The Cu(II) and Gd(III) complexes showed strong cytotoxicity in MTT assays against MCF-7 (IC₅₀ = 0.65 and 0.80 µM) and HepG-2 (IC₅₀ = 1.00 and 2.47 µM) cell lines, significantly surpassing the HDN ligand and standard drugs such as 5-fluorouracil (IC₅₀ = 3.95 µM, MCF-7) and cisplatin (IC₅₀ = 15.24 µM, MCF-7)...The present results provide a preclinical proof-of-concept for diclofenac-derived Schiff base metal complexes as dual anti-inflammatory and anticancer agents. However, their therapeutic potential remains to be validated through stability, mechanistic, and in vivo investigations."

Journal • Oncology

Cyclooxygenase-2 inhibition improves hypercholesterolemia-induced cardiac dysfunction. (PubMed, Biomed Pharmacother) - "Cdc42ep4, Cox5, and Cxcl9 genes were also counter-regulated following rofecoxib treatment compared to HC-induced changes. This is the first demonstration that rofecoxib improves HC-induced cardiac dysfunction, with the mechanism involving changes in the gene expression profile, including some key regulators of rofecoxib action."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • Reperfusion Injury • CXCL9 • MIR27A • MIR30D

Kidney Safety of Nonsteroidal Anti-Inflammatory Drugs in Patients with Arthritis: A Network Meta-Analysis (KIDNEY WEEK 2025) - "NSAIDs evaluated were naproxen (n=17,185), ibuprofen (n=28,531), celecoxib (n=37,843), oral diclofenac (n=6,060), rofecoxib (n=804), nabumetone (n=15), valdecoxib (n=544), and amtolmetin guacil (n=30)...Conclusion Rofecoxib, naproxen, and diclofenac are associated with a higher incidence of renal AEs, edema, and HTN compared with placebo, respectively. Physicians should weigh renal safety when prescribing NSAIDs for arthritis."

Retrospective data • Immunology • Osteoarthritis • Rheumatoid Arthritis • Rheumatology

Lipid Raft Membrane Interactivity Correlating with Cyclooxygenase-2 Selectivity of Non-Steroidal Anti-Inflammatory Drugs. (PubMed, Membranes (Basel)) - "Conventional NSAIDs (diclofenac, ibuprofen, indomethacin, aspirin, and flurbiprofen) and Coxibs (lumiracoxib, etoricoxib, celecoxib, valdecoxib, and rofecoxib) decreased membrane fluidity, whereas Oxicams (meloxicam, piroxicam, tenoxicam, and lornoxicam) increased. Under inflammatory acidic conditions, the lipid raft membrane interactivity of NSAIDs was more likely to correlate with cyclooxygenase-2 selectivity than the reference membrane interactivity. It is hypothesized that NSAIDs may interact with lipid raft membranes to induce membrane fluidity changes with the potency corresponding to cyclooxygenase-2 inhibition, disrupting the structural and functional integrity of lipid rafts to affect the activity of cyclooxygenase-2 localized in lipid rafts, resulting in cyclooxygenase-2 selective inhibition."

Journal

Primary Stabbing Headache: A Narrative Review of an Underrecognized Pain Syndrome (IHC 2025) - "Pharmacological treatments identified across studies included COX-2 inhibitors, indomethacin, paracetamol, celecoxib, melatonin, gabapentin, nifedipine, and rofecoxib. Despite being a benign and self-limiting headache disorder, PSH still presents diagnostic challenges due to its atypical presentation and lack of specific biomarkers. Further clinical and pathophysiological research is warranted to improve diagnostic precision and to evaluate the efficacy and safety of currently used pharmacological interventions."

Review • CNS Disorders • Migraine