- |||||||||| Tabrecta (capmatinib) / Incyte, Novartis, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Symproic (naldemedine) / Shionogi, Collegium Pharma
Journal: Multi-targeted drug repurposing approach for breast cancer via integrated functional network analysis. (Pubmed Central) - Aug 12, 2022 The effect of Pimozide on EMT-induced MDAMB231 and MDAMB468 cells was evident from their IC50 values of 7.85 µM and 6.83 µM, respectively. The potent anti-cancer property of Pimozide has opened up avenues for drug repurposing towards 'multi-targeted therapy' in EMT dynamics.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
Journal: Efficacy Survey of Naldemedine in the Poor-performance Status Group (Pubmed Central) - Jul 6, 2022 Furthermore, results of multivariate analysis showed that "best supportive care" and "body weight (55 kg and above)" reduced Nal efficacy. In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
Retrospective data, Journal: Nalmedine-laxative combination: retrospective inpatient study. (Pubmed Central) - Jun 25, 2022 In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS. The introduction of naldemedine alone or in combination with MgO should be considered.
- |||||||||| Review, Journal: Constipation in Cancer Patients - an Update of Clinical Evidence. (Pubmed Central) - Jun 11, 2022
Naldemedine, naloxegol, and methylnaltrexone are supported by quality evidence for OIC management. Naloxone or naltrexone, taken orally in combined formulations with opioids, may be valuable in preventing or reducing OIC symptoms.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
Retrospective data, Journal: Risk factors for opioid-induced constipation in cancer patients: a single-institution, retrospective analysis. (Pubmed Central) - May 31, 2022 Naloxone or naltrexone, taken orally in combined formulations with opioids, may be valuable in preventing or reducing OIC symptoms. High BMI, chemotherapy including a taxane within 1 month of evaluation of laxative effect, no use of naldemedine, and addition or switching due to insufficient prior laxatives were identified as risk factors for OIC in advanced cancer patients with cancer pain.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
Review, Journal: Update on the role of naldemedine in opioid-induced constipation in patients with chronic noncancer pain. (Pubmed Central) - May 6, 2022 It is generally well tolerated with a higher incidence of gastrointestinal adverse events of mild or moderate severity such as diarrhea, abdominal pain, or vomiting compared to placebo. While there are no randomized, controlled trials that compare head-to-head pharmacological therapies used for treatment of OIC, network meta-analysis shows that naldemedine has an overall good benefit-risk profile compared to the other approved medications.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date: Effects of a Peripherally Acting (clinicaltrials.gov) - Mar 8, 2022 P2/3, N=120, Recruiting, Based on data derived from the anchor method, reductions in PAC-SYM and PAC-QOL scores of >1.0 in patients with chronic non-cancer pain and OIC are clinically meaningful. Not yet recruiting --> Recruiting | Trial completion date: Apr 2023 --> Jun 2023 | Initiation date: Oct 2021 --> Jan 2022 | Trial primary completion date: Apr 2023 --> Jun 2023
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
Journal: Naldemedine for opioid-induced constipation. (Pubmed Central) - Mar 3, 2022 It must be discontinued if treatment with the opioid is discontinued. Cost: £41.72 for 28 tablets Classification: Prescription only medicine subject to additional monitoring (▼).
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
Retrospective data, Journal: Factors affecting the effect of naldemedine for opioid-induced constipation: a single-institution, retrospective analysis. (Pubmed Central) - Dec 18, 2021 Multivariate ordered logistic regression analysis was conducted to identify factors affecting the effect of naldemedine. Use of naldemedine within 2 days of opioid initiation [odds ratio (OR) =0.346, 95% confidence interval (CI) =0.173-0.693; P = 0.003], concomitant use of anticholinergics (OR = 2.033, 95% CI = 1.150-3.594; P = 0.015), tramadol (OR = 0.488, 95% CI = 0.250-0.953; P =0.036), and chronic non-cancer pain (OR = 0.429, 95% CI = 0.197-0.937; P = 0.034) were identified as significant factors related to the effect of naldemedine.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
Journal: Naldemedine for the Use of Management of Opioid Induced Constipation. (Pubmed Central) - Dec 16, 2021 Naldemedine is an FDA-approved, once-daily oral tablet that counteracts this side effect by antagonizing mu, kappa, and delta-opioid receptors and has been shown to be safe and effective. Further investigation including head-to-head clinical trials are required to evaluate the relative efficacy of naldemedine compare with other peripheral opiate receptor antagonists.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
Biomarker, Journal: Analysis of Predictive Factors for Diarrhea after the Administration of Naldemedine. (Pubmed Central) - Dec 16, 2021 Therefore, the development of diarrhea needs to be considered in patients with these risk factors. Furthermore, diarrhea may be controlled by the initiation of NAL within 7 d of opioid analgesics and, where possible, the discontinuation of or change in the combination of moderate or strong CYP3A4 inhibitors.
- |||||||||| lumacaftor (VX-809) / Vertex, Symproic (naldemedine) / Shionogi, BDSI, Promacta (eltrombopag) / Novartis
Biomarker, Journal: Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke. (Pubmed Central) - Oct 30, 2021 Several potential therapeutic compounds corresponding to MAP1LC3B, PTGS2, and TLR4 were also identified for ischemic stroke, including Zinc12503187 (Conivaptan), Zinc3932831 (Avodart), Zinc64033452 (Lumacaftor), Zinc11679756 (Eltrombopag), Zinc100378061 (Naldemedine), and Zinc3978005 (Dihydroergotamine). Our results suggested MAP1LC3B, PTGS2, and TLR4 as potential diagnostic biomarkers for ischemic stroke, providing more evidence about the vital role of ferroptosis in ischemic stroke.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI, Movantik (naloxegol) / AstraZeneca, RedHill, Kyowa Kirin, Relistor (methylnaltrexone bromide) / Ono Pharma, Progenics, Bausch Health
Reimbursement, Journal, Medicare: Use of Peripheral μ-Opioid Receptor Antagonists for Treating Opioid-Induced Constipation among US Medicare Beneficiaries from 2014 to 2018. (Pubmed Central) - Aug 12, 2021 Three PAMORAs are U.S. Food and Drug Administration approved for managing OIC-methylnaltrexone (FDA approved in 2008), naloxegol (in 2014), and naldemedine (in 2017). Our findings-significant and increasing expenditure on PAMORAs, and broad use across specialties-serve as a call for defining and implementing appropriate use of PAMORAs.
- |||||||||| Review, Journal: Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel. (Pubmed Central) - Aug 7, 2021
Second-line treatment with a peripherally acting μ opioid receptor antagonist (PAMORA), such as methylnaltrexone, naloxegol or naldemedine, should be considered in patients with OIC that has not responded to combination laxative treatment. Prokinetics or intestinal secretagogues, such as lubiprostone, may be appropriate in the third-line setting, but their use in OIC is off-label in Italy, and should therefore be restricted to settings such as specialist centres and clinical trials.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
New P2/3 trial: Effects of a Peripherally Acting (clinicaltrials.gov) - Jul 18, 2021 P2/3, N=130, Not yet recruiting,
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI, Relistor (methylnaltrexone bromide) / Ono Pharma, Progenics, Bausch Health
Clinical, Review, Journal, HEOR: Opioid-Induced Constipation: A Review of Health-Related Quality of Life, Patient Burden, Practical Clinical Considerations, and the Impact of Peripherally Acting μ-Opioid Receptor Antagonists. (Pubmed Central) - Jul 16, 2021 PAMORAs provide effective relief of OIC while also improving QOL. To augment the pharmacologic management of OIC, proactive counseling approaches between physicians and patients may help relieve some of the patient burden associated with OIC and lead to improved outcomes.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
Journal, Adverse events: Naldemedine: Peripherally-acting Opioid Receptor Antagonist for Treating Opioid-induced Adverse Effects. (Pubmed Central) - Jul 3, 2021 Further improvement in the potency and pharmacokinetic profiles of the lead compound led to the discovery of naldemedine, which showed anti-constipation and anti-emetic effects against these adverse events that were induced by morphine without influencing morphine's analgesic effect. Naldemedine was launched in Japan and the USA in 2017 and in the EU in 2019 for treating opioid-induced constipation.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
[VIRTUAL] EFFICACY AND SAFETY OF NALDEMEDINE IN CANCER PATIENTS NEEDING PALLIATIVE CARE () - Jun 29, 2021 - Abstract #MASCCISOO2021MASCC_ISOO_614; Subgroup analyses were performed for naldemedine monotherapy (Group N) versus combined naldemedine and stimulant laxatives (Group C). Group C showed a non-significant tendency toward being older than Group N. No significant differences were seen in opioid use, BM frequency before taking naldemedine, or duration of opioid administration between Groups N and C. Conclusion Naldemedine is useful in the management of OIC among advanced cancer patients, but combination therapy with stimulant laxatives is sometimes required.
- |||||||||| imatinib / Generic mfg.
Preclinical, Journal: Antiviral drug design based on the opening mechanism of spike glycoprotein in SARS-CoV-2. (Pubmed Central) - Jun 16, 2021 FDA approved drug molecules were screened by their capabilities of blocking the formation of the key pair of salt bridges, achieved by their positional stabilities in the cavity containing the side chains of K537 and E619 formed in the interface between SD1 and SD2. Simeprevir, imatinib, and naldemedine were identified to possess the desired capability with the most favorable interaction energies.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI
Clinical, PK/PD data, Journal: The Influence of Renal or Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Naldemedine. (Pubmed Central) - May 29, 2021 In subjects with hepatic impairment compared with healthy subjects with normal hepatic function, the geometric mean ratio of AUC ranged from 82.8% (90%CI 65.7% to 104.5%) to 105.2% (90%CI 83.4% to 132.6%). Naldemedine was well tolerated in both healthy subjects and subjects with renal or hepatic impairment, and reported adverse events were generally consistent with the known safety profile.
- |||||||||| Symproic (naldemedine) / Shionogi, BDSI, Movantik (naloxegol) / AstraZeneca, RedHill, Kyowa Hakko Kirin, Relistor (methylnaltrexone bromide) / Ono Pharma, Progenics, Bausch Health
Clinical, Review, Journal: Opioid-Induced Constipation in Advanced Cancer Patients. (Pubmed Central) - Apr 16, 2021 Pharmacological treatments involve the use of traditional laxatives and newer agents like peripherally acting mu-opioid receptor agonists (PAMORAs), including naldemedine, naloxegol, and methylnaltrexone. More novel treatments for OIC that target the pathophysiology are still needed and should be studied carefully for safety and efficacy.
- |||||||||| Symproic (naldemedine) / Shionogi, Collegium Pharma
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Surgery: A Study of Naldemedine in Participants Undergoing Surgeries That Include a Bowel Resection or Bowel Transection (clinicaltrials.gov) - Feb 2, 2021 P2, N=2, Terminated, The aim of this narrative review to update the current status of PAMORAs for treating OIC in terms of safety and efficacy. N=340 --> 2 | Trial completion date: Jan 2022 --> Jan 2021 | Recruiting --> Terminated | Trial primary completion date: Nov 2021 --> Jan 2021; This study was terminated before the planned sample size was enrolled due to very slow enrollment.
- |||||||||| Clinical, Review, Journal: Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols. (Pubmed Central) - Jan 5, 2021
These include 5HTR agonists (Prucalopride and TAK 954), vagus nerve stimulation of the ENS-macrophage nAChR cholinergic pathway, acupuncture, herbal medications, peripheral acting opioid antagonists (Alvimopen, Methlnaltexone, Naldemedine), anti-bloating/flatulence drugs (Simethiocone), a ghreline prokinetic agonist (Ulimovelin), drinking coffee, and nicotine chewing gum. A better understanding of the pathogenic mechanisms for short and long-term outcomes is necessary before we can develop better prophylactic and treatment strategies.
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