Symproic (naldemedine) / Shionogi, Collegium Pharma - LARVOL DELTA

PS04 Peripheral opioid pathway antagonists: a novel therapy for idiopathic chronic pruritus and nodular prurigo. (PubMed, Br J Dermatol) - "Naloxegol and naldemedine are peripherally acting μ-opioid receptor antagonists used in the treatment of opioid-induced constipation. Only one patient reported mild gastrointestinal side-effects immediately after commencing therapy; however, they continued with treatment and this subsided shortly after. These results suggest that peripheral μ-opioid receptor antagonists have the potential to be an effective treatment option for chronic pruritus; however, further studies are needed to confirm their efficacy."

Journal • CNS Disorders • Constipation • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Prurigo Nodularis • Pruritus

Establishing the minimal important change for Patient Assessment of Constipation Quality of Life questionnaire for the prevention of opioid-induced constipation in patients with cancer pain. (PubMed, Support Care Cancer) - "The MIC values for the PAC-QOL scales for OIC prevention ranged from 0.14 to 0.41 for the overall scale and from 0.20 to 1.80 for the satisfaction subscale. These findings enable the assessment of the preventive effect of interventions for OIC in patients initiating opioids for cancer pain."

Clinical • HEOR • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain • Palliative care

NOCON: Naldemedine in Clinical Practice in Cancer Patients With Opioid Induced Constipation: Clinical Outcomes and Patient Experience (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Professor Monique A. H. Steegers

New trial • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology

Naldemedine (Rizmoic®) for the treatment of opioid-induced constipation (PubMed, Rev Med Liege) - "Effectively managing pain also means paying attention to adverse effects such as OIC, which can impact patients' quality of life. In addition to traditional treatments, therapeutic alternatives like naldemedine, a selective peripherally acting μ-opioid receptor antagonist, are now available to help patients for whom standard solutions are insufficient."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Opioid-induced constipation in internal medicine: recognition and management pathways. (PubMed, Intern Emerg Med) - "In conclusion, we urge to expand awareness about OIC. The seven-step diagnostic-therapeutic pathway approach formulated by ECHO OIC is a pragmatic and scalable model to improve OIC management with emphasis on education, early intervention, monitoring, tailored pharmacologic strategies, and coordinated referral when necessary."

Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder

Naldemedine for the management of opioid-induced constipation in patients with cancer pain: A narrative review. (PubMed, Medicine (Baltimore)) - "A comprehensive search was conducted to identify primary articles on the clinical effectiveness and adverse effects of naldemedine in patients with cancer with OIC. Naldemedine is a well-tolerated and effective drug for treatment of OIC in patients with cancer, and its use is expected to increase."

Journal • Review • Addiction (Opioid and Alcohol) • Anesthesia • Constipation • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Oncology • Pain

Prophylactic Use of Naldemedine on Opioid-induced Nausea and Vomiting in Patients With Cancer: POSEIDON Study (clinicaltrials.gov) - P4 | N=120 | Recruiting | Sponsor: International University of Health and Welfare

New P4 trial • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology

Treatment of Opioid-Induced Constipation: Inducing Laxation and Understanding the Risk of Gastrointestinal Perforation. (PubMed, J Clin Gastroenterol) - "Management of OIC includes treatment with over-the-counter laxatives and peripherally acting μ-opioid receptor antagonists (PAMORAs; methylnaltrexone, naloxegol, naldemedine). Appropriate patient selection during laxation therapy for OIC, regardless of treatment plan, involves consideration of the overall risk versus benefit in patients at increased risk of perforation due to comorbid medical conditions, concurrent medications, or recent gastrointestinal procedures. After initiating treatment for OIC, clinicians should assess the effectiveness of laxation therapy and carefully monitor for signs of gastrointestinal perforation."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Factors for Discontinuation of Naldemedine Therapy in a Palliative Ward. (PubMed, In Vivo) - "A high CAR (≥0.888) was a risk factor for the discontinuation of naldemedine therapy in a palliative ward. Our results suggest that physicians and pharmacists should monitor CAR as a marker of malnutrition and systemic inflammation before initiating naldemedine therapy."

Journal • Cachexia • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain • CRP

Efficacy of Naldemedine in opioid-induced constipation in cancer patients (PubMed, Zhonghua Yi Xue Za Zhi) - "Naldemedine improved QoL. Naldemedine shows promising efficacy and manageable safety in cancer pain patients with OIC."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain

Drug repositioning as a promising approach for the eradication of emerging and re-emerging viral agents. (PubMed, Mol Divers) - "Main repositioned drugs have included chloroquine, ivermectin, dexamethasone, Baricitinib, tocilizumab, Mab114 (Ebanga™), ZMapp (pharming), Artesunate, imiquimod, saquinavir, capmatinib, naldemedine, Trametinib, statins, celecoxib, naproxen, metformin, ruxolitinib, nitazoxanide, gemcitabine, Dorzolamide, Midodrine, Diltiazem, zinc acetate, suramin, 5-fluorouracil, quinine, minocycline, trifluoperazine, paracetamol, berbamine, Nifedipine, and chlorpromazine. This succinct review will delve into the topic of repositioned drugs that have been utilized to combat emerging and re-emerging viral pathogens."

Journal • Review • Chikungunya • Dengue Fever • Ebola Virus Disease • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Timing of Naldemedine Initiation and Occurrence of Diarrhea in Patients Receiving Strong Opioid Analgesics: A Retrospective Study. (PubMed, Pharmacy (Basel)) - "Multivariate logistic regression analysis revealed that the delayed introduction of naldemedine was significantly associated with the development of diarrhea (odds ratio: 6.68, 95% confidence interval: 1.220-36.700, p = 0.028). Our analysis reveals that the simultaneous administration of naldemedine and oxycodone may prevent the development of diarrhea associated with naldemedine use for OIC."

Journal • Retrospective data • Addiction (Opioid and Alcohol) • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Erratum: Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial. (PubMed, J Clin Oncol) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology

Opioid withdrawal syndrome induced by naldemedine administration in a cancer patient without brain metastasis. (PubMed, Palliat Support Care) - "Even in patients without brain metastasis, naldemedine can induce opioid withdrawal symptoms, so caution is required with patients receiving this drug. In addition, when psychiatric symptoms are pronounced, as in this case, withdrawal symptoms may be underdiagnosed."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Hepatology • Liver Cancer • Mood Disorders • Oncology • Pain • Psychiatry • Solid Tumor

Naldemedine Use and Healthcare Resource Utilization in Patients treated with Opioid Analgesics for Chronic Non-Cancer Pain: Results of a Real-world Study in the USA. (PubMed, Pain Ther) - "This real-world study demonstrates that naldemedine is predominantly used in middle-aged adults with comorbidities and polypharmacy. Naldemedine use was associated with reduced HCRU, particularly in older adults, suggesting potential benefits in managing OIC. The findings support the safety and effectiveness of naldemedine in real-world settings, including in older patients with multiple comorbidities."

HEOR • Journal • Real-world evidence • Back Pain • Cardiovascular • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Hypertension • Metabolic Disorders • Musculoskeletal Pain • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • CYP3A4

Drug-associated pancreatic cancer: insights from real-world pharmacovigilance and network pharmacology. (PubMed, Expert Opin Drug Saf) - "Except 4 antineoplastic agents, only 24 drugs indicated pancreatic cancer signals in 33,948 reports including 4 dipeptidyl peptidase-4 (DPP-4) inhibitors, 3 glucagon-like peptide-1 (GLP-1) analogues, 5 compound hypoglycemic agents, 3 hypotensive agents, ranitidine, pancrelipase, fondaparinux, naldemedine, daprodustat, megestrol acetate, leuprorelin, lecanemab, and lorcaserin. GLP1R (glucagon-like peptide 1 receptor) for GLP-1analogues, and PTEN (phosphatase and tensin homolog) for metformin might be a potential cause of pancreatic cancer. Clinicians providing these therapies should stay vigilant to detect pancreatic cancer early."

Adverse events • Journal • Real-world evidence • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • PTEN

Prescription Pattern of Laxatives for Opioid-Induced Constipation in Japanese Patients With Chronic Non-cancer Pain: A Retrospective Cohort Study of a Health Insurance Claims Database. (PubMed, Cureus) - "Most were prescribed ≤150 mg tramadol equivalent/day, and 21,405 (50.3%) were on weak opioids for lower back pain...The most common laxatives during the first week were magnesium oxide (2,320 (66.6%)), sennoside (484 (13.9%)), and naldemedine (301 (8.6%)); at 12 weeks, these proportions were 55.2%, 13.1%, and 13.8%, respectively.​ The amount of weak opioids prescribed to patients without laxatives was lower than the standard dosage and was also lower than the amount prescribed to patients with laxatives. Conclusions This study showed that the actual prescription patterns of laxatives after initiating weak opioids in patients with chronic non-cancer pain were variable, depending on the duration after initiating weak opioids. The association between laxative use and weak opioid dosage indicates that OIC management may have a potential impact on pain management."

Journal • Reimbursement • Retrospective data • US reimbursement • Back Pain • Constipation • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Oncology • Pain

Post-marketing safety assessment of constipation drugs: a real-world pharmacovigilance study based on FAERS database. (PubMed, Expert Opin Drug Saf) - "We conducted a pharmacovigilance analysis based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database to analyze the adverse events of six constipation drugs (linaclotide, lubiprostone, prucalopride, naloxegol, naldemedine, and plecanatide) and to search for clinically meaningful adverse reaction signals. The adverse reactions of constipation drugs were mainly gastrointestinal symptoms such as diarrhea, abdominal pain and abdominal distension. Linaclotide has the highest safety, and more studies are needed to analyze the cardiovascular safety of lubiprostone."

Adverse events • Journal • P4 data • Real-world evidence • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Breaking the Phalanx: Overcoming Bacterial Drug Resistance with Quorum Sensing Inhibitors that Enhance Therapeutic Activity of Antibiotics. (PubMed, bioRxiv) - "Amongst explored drug combinations, 31 exhibited a synergistic effect, including mixtures involving naldemedine and telotristat, two drugs predicted by our model with previously undescribed QSI activity. Although no mixture inhibiting all the strains was found, piperacillin combined with curcumin, ketoprofen, indomethacin, and piroxicam demonstrated the broadest antimicrobial action. We anticipate that further preclinical investigation of these combinations of novel repurposed QSIs with a known antibiotic may lead to novel clinical candidates."

Journal • Infectious Disease

Safety of Naldemedine for Opioid-Induced Constipation - A Systematic Review and Meta-Analysis. (PubMed, J Pain Palliat Care Pharmacother) - "This analysis confirms naldemedine's overall safety in treating opioid-induced constipation, with manageable gastrointestinal side effects. However, the higher adverse events in cancer patients require further investigation to ensure safe use in this population."

Journal • Retrospective data • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain

Naldemedine Without Rescue Laxatives Versus Either Laxatives or Naloxegol in the Treatment of Opioid Induced Constipation Among Adults With Chronic Non-Cancer Pain (ISPOR-EU 2024) - "In patients with OIC and chronic non-cancer pain, naldemedine proved superior to not only rescue laxatives when used either as monotherapy or in combination with an established laxative regimen but also to naloxegol 25mg monotherapy in LIR patients."

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain

A multicenter study of naldemedine in cancer patients with opioid-induced constipation consisting of a placebo-controlled study period followed by an open study period (ChiCTR) - P3 | N=120 | Completed | Sponsor: The Second Hospital of Anhui Medical University; Ping An-Shionogi Co., Ltd.

New P3 trial • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology

Characteristics of Patients Prescribed Naldemedine in United Kingdom Primary Care: An Observational Retrospective Cohort Study (ISPOR-EU 2024) - "This study profiles naldemedine use in UK primary care. The majority of patients had received opioids before the initial naldemedine prescription. Over half had a record of cancer in the previous 12 months, and almost a third had a code indicative of surgery in the previous month."

Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology

Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Shionogi | Trial completion date: Aug 2024 ➔ Jun 2026 | Trial primary completion date: Aug 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

Effect of add-on naldemedine treatment in patients with cancer and opioid-induced constipation insufficiently responding to magnesium oxide: a pooled, subgroup analysis of two randomized controlled trials. (PubMed, Jpn J Clin Oncol) - "The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment."

Clinical • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology