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

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

Emerging therapies for opioid-induced constipation: what can we expect? (PubMed, Expert Opin Pharmacother) - "Key topics included the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) such as methylnaltrexone, naloxegol, and naldemedine, which specifically target opioid-induced gut dysfunction. Other treatment options, including intestinal secretagogues like lubiprostone and linaclotide, selective 5-HT receptor agonists such as prucalopride, and emerging adjunctive therapies like transcutaneous electrical nerve stimulation (TENS) and electroacupuncture were mentioned...Emerging therapies and adjunctive treatments offer promising results but require further validation through rigorous studies. Future research should focus on long-term outcomes, cost-effectiveness, and comparative effectiveness to better address the complex needs of patients with OIC and refine treatment protocols."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial. (PubMed, J Clin Oncol) - "Naldemedine prevented constipation and improved constipation-related QOL, with possible preventive effect on OINV in patients with cancer starting regularly dosed opioids therapy."

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

Experience with naldemedine in opioid-induced constipation in oncologic patients with chronic pain. (PubMed, Med Clin (Barc)) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Naldemedine-induced perforation of a diverticulum in the sigmoid colon of a patient with opioid-related constipation: a case report. (PubMed, J Pharm Health Care Sci) - "These results suggest that the effects of OIC may have compressed the intestinal tract, which was followed by naldemedine-activation of peristalsis, which led to the onset of intestinal perforation. In patients with pre-existing diverticular disease, we should monitor for increased WBC counts and CRP levels after the initiation of treatment with naldemedine, and consider performing appropriate tests early in the event of abdominal complaints."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Head and Neck Cancer • Oncology • Oral Cancer • Pain • Solid Tumor • CRP

The prevalence of tapentadol-induced constipation following cancer pain treatment (IASP 2024) - "The present study was performed to clarify the prevalence of OIC caused by tapentadol for cancer pain treatment under the hypothesis that OIC would be reversed by naldemedine, peripheral opioid receptor antagonist. Present study clearly demonstrates that the prevalence of tapentadol-induced constipation was low. More than half patients have not revealed constipation during tapentadol treatment, although the prevalence of chronic constipation since before was 34.8% (8/23). We conclude tapentadol should be prescribed for cancer pain treatment because of a high effectivity and better gastrointestinal tolerability profile."

Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain

Efficacy and Safety of Naldemedine for Opioid-Induced Constipation in Children. (PubMed, J Palliat Med) - "In some patients, grade 2 diarrhea required naldemedine discontinuation, suggesting that it should be used with caution in pediatric patients. Further studies are warranted to determine the optimal naldemedine dose in pediatric patients."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Pediatrics

A peripherally acting μ-opioid receptor antagonist for treating opioid-associated tinnitus: A case report. (PubMed, Palliat Med) - "Although peripheral tinnitus disappeared after discontinuing oxycodone, it reappeared with hydromorphone or tapentadol administration...Based on the presumed mechanism of peripheral tinnitus, the use of peripherally acting μ-opioid receptor antagonists was planned, and 200 μg/day of naldemedine was prescribed for tinnitus relief...The use of peripherally acting μ-opioid receptor antagonists may be an option to treat opioid-associated tinnitus without compromising the analgesic effects. Further clinical data regarding the secondary effect of peripherally acting μ-opioid receptor antagonists on opioid-associated complications other than constipation are required."

Journal • Constipation • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Otorhinolaryngology • Pain • Pancreatic Cancer • Solid Tumor

The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study. (PubMed, Support Care Cancer) - "Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings."

Journal • Metastases • Observational data • Real-world • Real-world evidence • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain • Palliative care • Urology

Preventive effect of naldemedine for opioid-induced constipation in patients with cancer starting opioids: A multicenter, double-blinded, randomized, placebo-controlled, phase 3 trial. (ASCO 2024) - "Naldemedine is a valuable option with proven efficacy in preventing OIC in cancer patients starting regular strong opioids."

Clinical • Late-breaking abstract • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Pain