Ryzolt (abuse resistant formulation) / Endo, Purdue - LARVOL DELTA

Comprehensive insights into diabetic peripheral neuropathy: pathophysiology and therapeutic approaches. (PubMed, J Diabetes Metab Disord) - "The United States Food and Drug Administration has approved pharmacological treatments for painful diabetic peripheral neuropathy: pregabalin, duloxetine, gabapentin, extended-release tapentadol, tramadol, and the capsaicin 8% patch. Non-Food and Drug Administration-approved therapies, such as amitriptyline and the 5% lidocaine patch, are also widely used...A multifaceted approach incorporating pharmacological and non-pharmacological therapies is essential for optimizing patient outcomes in diabetic peripheral neuropathy. Targeting underlying pathophysiological mechanisms while providing symptomatic relief can enhance treatment efficacy and improve the quality of life for individuals with diabetic peripheral neuropathy."

Journal • Review • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Medical College of Wisconsin | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Mucositis • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Trends in Outpatient Buprenorphine Prescribing for Chronic Pain: A Retrospective Analysis Over 18 Months. (PubMed, Psychopharmacol Bull) - "Long-acting opioids analyzed included extended release (ER) formulations including tramadol ER, morphine ER, hydrocodone ER, oxycodone ER, fentanyl, and methadone. The proportion of buprenorphine prescriptions relative to long-acting opioids increased over time, suggesting growing acceptance of buprenorphine as a safer alternative for chronic pain management. Further research is needed to explore the factors driving these prescribing patterns and the long-term clinical outcomes associated with buprenorphine use in chronic pain management."

Journal • Retrospective data • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Pain • Psychiatry • Substance Abuse

Tapentadol: A Comprehensive Review of Its Role in Pain Management. (PubMed, Cureus) - "Approved by the FDA in 2008 for immediate release and in 2011 for extended release, tapentadol effectively addresses both nociceptive and neuropathic pain, offering a more favorable efficacy-safety profile compared to traditional opioids such as tramadol. Additionally, tapentadol is gaining recognition as a preferred option for managing significant pain in cancer patients due to its effectiveness and reduced side effects. This review evaluates tapentadol's clinical and pharmacological attributes, systematically analyzing literature on its efficacy, safety, pharmacokinetics, and comparative effectiveness, suggesting that tapentadol is a viable option for effective pain management with potential for broader clinical applications."

Journal • Review • Neuralgia • Oncology • Pain

The Analgesic and Side Effects of Tramadol Hydrochloride Immediate-Release and Extended-Release Tablets in Patients With Chronic Low Back Pain. (PubMed, Cureus) - " This study shows the incidence of side effects following the administration of tramadol hydrochloride immediate-release and extended-release tablets. Regarding the breakdown of side effects, constipation, nausea, drowsiness, and dizziness were noted. Regarding pain evaluation, we found a significant reduction in the VAS scores for low back pain from baseline after four weeks of treatment, suggesting that tramadol hydrochloride immediate-release and extended-release tablets may provide excellent analgesic effects owing to their pharmacokinetic properties that ensure stable tramadol concentrations in the bloodstream."

Adverse events • Journal • Back Pain • Constipation • Gastroenterology • Gastrointestinal Disorder • Lumbar Back Pain • Musculoskeletal Pain • Pain

The influence of tramadol on bowel function: A randomised, placebo-controlled trial. (PubMed, Basic Clin Pharmacol Toxicol) - "Additionally, more participants fulfilled the diagnostic criteria for constipation after tramadol treatment compared to placebo (40% vs. 0%, p < 0.001). This study showed that tramadol treatment is associated with OIBD, and management of constipation and other bowel symptoms should, therefore, be prioritised when treating pain patients with tramadol."

Journal • Constipation • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Pain

LOW-DOSE BUPRENORPHINE IN CHRONIC NONMALIGNANT PAIN (IASP 2024) - "This new form of transdermal buprenorphine is well tolerated, even in patients who reported intolerance to tramadol or other opioids. The overall incidence of adverse events has been low, although the follow-up period for patients is still relatively short. On the other hand, however, the incidence of local reactions may be overestimated by the hot summer currently underway."

Back Pain • CNS Disorders • Dermatology • Dyspepsia • Epilepsy • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Osteoarthritis • Pain • Pruritus • Rheumatology

Chitosan-PVA-PVP/nano-clay composite: a promising tool for controlled drug delivery. (PubMed, RSC Adv) - "Tramadol was used as a model drug to assess the efficacy of these ternary blends as drug delivery systems...Furthermore, the nanoclay-reinforced composite showed high permeation. Based on the obtained results, it can be concluded that the produced nanocomposite could be used as an efficient transdermal drug delivery system."

Journal

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Medical College of Wisconsin | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Mucositis • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

The impact of tightened prescribing restrictions for PBS-subsidised opioid medicines and the introduction of half-pack sizes, Australia, 2020-21: an interrupted time series analysis. (PubMed, Med J Aust) - "The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS-subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions."

Journal • Pain

Major depressive episode in the elderly. Use of maintenance ECT: a case report. (EPA 2024) - "Femoral head fracture, myelodysplastic syndrome, severe osteoporosis with vertebral crushing, requiring rescue treatment with tramadol, and renal failure...Despite antidepressant and stabilising treatment with duloxetine at daily doses of 120mg, extended-release quetiapine 600mg, lorazepam 2.5mg and mirtazapine 45mg, the patient began to show negative behaviour towards accepting food, clinophilic behaviour and abandonment, which led to her being admitted to the short-term hospitalisation unit... ECT is indicated in severe depression, with or without psychotic symptoms, with malnutrition and organic pathology. According to studies, it has a beneficial response of more than 60%. However, the rate of receiving depressive symptomatology in a severe episode is high, despite ECT, so studies and clinical practice recommend maintenance ECT."

Clinical • Anorexia • CNS Disorders • Depression • Psychiatry

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Medical College of Wisconsin | Trial completion date: Mar 2025 ➔ Sep 2025

Trial completion date • Head and Neck Cancer • Mucositis • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Eliminating Extended-Release Opioids from a Postoperative Pain Protocol for Total Knee Replacement Patients. (PubMed, Pain Manag Nurs) - "All patients received 30 tablets of only one opioid prescription upon discharge with no refill, either oxycodone-IR (82%, n = 49), hydromorphone (5%, n = 3), or tramadol (12%, n = 7). The project, aimed to reduce opioid overprescription and overconsumption, has the potential to improve prescribing practices, promoting patient safety and healthcare quality by supporting the current guidelines that recommend against using ER opioids for the study population."

Journal • Musculoskeletal Diseases • Orthopedics • Pain

Development, Physicochemical Characteristics and Pharmacokinetics of a New Sustained-Release Bilayer Tablet Formulation of Tramadol with an Immediate-Release Component for Twice-Daily Administration. (PubMed, Eur J Drug Metab Pharmacokinet) - "To address the potential concerns regarding existing formulations of tramadol, a twice-daily, extended-release bilayer formulation of tramadol consisting of an IR and SR layer was developed. Pharmacokinetic studies confirmed that the plasma tramadol concentration increased quickly after administration and was maintained over a long period of time."

Journal • PK/PD data • Pain

Pharmacobezoar-Related Fatalities: A Case Report and a Review of the Literature. (PubMed, Ther Drug Monit) - "Her usual treatment included tramadol extended-release, citalopram, and mirtazapine...Tramadol (34,000 mcg/L), O-desmethyltramadol (2200 mcg/L), propranolol (6000 mcg/L), bromazepam (2500 mcg/L), zopiclone (1200 mcg/L), and citalopram (700 mcg/L) were identified in femoral blood at toxic concentrations...A mixed cause of death was reported in 2 cases. Although rare, pharmacobezoars remain potentially lethal and raise challenges in therapeutic management."

Journal • Review • Infectious Disease • Septic Shock

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Medical College of Wisconsin | Trial completion date: Aug 2024 ➔ Mar 2025 | Trial primary completion date: Aug 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Head and Neck Cancer • Mucositis • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A novel pH-responsive hydrogel system based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential candidate for controlled drug delivery. (PubMed, Eur J Pharm Sci) - "Tramadol hydrochloride (THC) was used as a model drug. Hence, pH-responsive swelling and release, non-toxic nature and improved pharmacokinetics support that PAG-based hydrogels may be considered as potential controlled-release polymeric carriers."

Journal

Risk of Hyponatremia after Tramadol/Acetaminophen Single-Pill Combination Therapy: A Real-World Study Based on the OMOP-CDM Database. (PubMed, Drugs R D) - "In this real-world study, hyponatremia was more frequently observed in the TA than AA group, and in the TA-ER than TA-IR subgroup. Therefore, it is imperative to prescribe tramadol cautiously and closely monitor electrolyte levels."

Combination therapy • Journal • Real-world • Real-world evidence • Cardiovascular • Heart Failure

Formulation of pH-responsive highly swellable hydrogel scaffolds for controlled release of tramadol HCl: characterization and biocompatibility evaluation. (PubMed, Front Bioeng Biotechnol) - "Moreover, oral toxicity studies were also conducted in rabbits to investigate the safety of hydrogels. No evidence of any toxicity, lesions and degeneration was reported, confirming the biocompatibility and safety of grafted system."

Journal • Pain

Risk of hyponatremia after tramadol/acetaminophen single-pill combination therapy: A real-world study based on the OMOP-CDM database (KSN 2023) - "In this real-world study, the risk of hyponatremia was higher in the TA than AA group,"

Clinical • Combination therapy • Real-world • Real-world evidence • Cardiovascular • Heart Failure

RISK OF HYPONATREMIA AFTER TRAMADOL/ACETAMINOPHEN SINGLE PILL COMBINATION MEDICATIONS: A REAL WORLD STUDY BASED ON THE OMOP-CDM DATABASE (ISN-WCN 2023) - "However, in patients with immediate-release users, the risk of hyponatremia was similar to those in acetaminophen users (HR 1.38 95%CI 0.68-2.89, p =0.38). Conclusions In this real-world study, the use of the extend-release formulation of Tramadol/Acetaminophen fixed-dose combination oral pill was associated with an increased risk of hyponatremia."

Clinical • Real-world • Real-world evidence • Cardiovascular • Heart Failure • Pain

Transdermal Buprenorphine for the Treatment of Radiation-Induced Mucositis Pain in Head and Neck Cancer Patients (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Medical College of Wisconsin | Trial completion date: Dec 2023 ➔ Aug 2024 | Trial primary completion date: Dec 2022 ➔ Aug 2023

Trial completion date • Trial primary completion date • Head and Neck Cancer • Mucositis • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™. (PubMed, Front Pharmacol) - "The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies."

Journal • PK/PD data

Enhanced recovery protocols improve patient outcomes in minimally invasive gynecologic surgery (UT Southwestern Medical Center) - "'The ERAS concept has been implemented in many surgical subspecialties with positive outcomes. Its application to minimally invasive gynecologic surgery is no different and has been shown to provide high-quality clinical care for patients,' said Lisa Chao, M.D...'The implementation of ERAS programs in minimally invasive gynecologic surgery results in substantial improvements in clinical outcomes with higher rates of same-day discharge, reduction in postoperative nausea and vomiting, improved patient satisfaction, and decreased opioid consumption without an increase in complications, readmissions, or health care costs,' said Dr. Chao."

Media quote

Multimechanistic Single-Entity Combinations for Chronic Pain Control: A Narrative Review. (PubMed, Cureus) - "Atypical opioids such as tramadol, tapentadol, and cebranopadol combine two complementary mechanisms of action into a single molecule, creating novel analgesic agents...Patients have been successfully rotated from one of these agents to another. All three agents show promise in the treatment of cancer and non-cancer pain and their unique formulation in a single molecule reduces the pill burden."

Journal • Review • Oncology • Pain