prucalopride / Generic mfg. - LARVOL DELTA

ANI Pharmaceuticals Announces the FDA Approval and Launch of Prucalopride Tablets with 180-Day CGT Exclusivity (GlobeNewswire) - "ANI Pharmaceuticals, Inc...today announced that following final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA), the Company has launched Prucalopride Tablets. ANI’s Prucalopride Tablets is the generic version of the reference listed drug (RLD) Motegrity...The FDA has granted our Prucalopride Tablets a Competitive Generic Therapy (CGT) designation, with 180-day exclusivity."

ANDA • Generic launch • Constipation

Single-Center Experience with Concomitant Use of Novel and Off-Label Prescriptions for Chronic Constipation (ACG 2024) - "Charts were reviewed for prescriptions of at least 1 of 8 pharmacotherapies: linaclotide, lubiprostone , plecanatide , prucalopride, tenapanor , tegaserod, pyridostigmine, and colchicine. 405 patients were evaluated for chronic constipation, of which 138 (34%) received one or more prescription-based therapies. The most common diagnoses supporting these prescriptions are listed in Table 1. 110 patients (79.7%) were prescribed monotherapy, 23 (16.67%) given dual therapy simultaneously, 4 (2.8%) given three agents simultaneously, and only 1 (0.7%) given four agents simultaneously."

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

Whole Gut Motility Patterns in Patients with Chronic Nausea and Vomiting. (PubMed, J Clin Med) - "In the patient group, our secondary aim was to explore how symptoms and motility patterns were affected by a serotonin HT4 receptor agonist (Prucalopride)... Patients with chronic N/V syndrome have significantly lower gastric contraction amplitude than HVs and may symptomatically benefit from prokinetics. They do not, however, have evidence of panenteric dysmotility."

Journal • Gastrointestinal Disorder

Human enteric glia diversity in health and disease: new avenues for the treatment of Hirschsprung disease. (PubMed, Gastroenterology) - "Two major enteric glial classes were identified in the pediatric intestine, highlighting the significant postnatal contribution of Schwann-like enteric glia to glial heterogeneity. Crucially, these glial subtypes persist in aganglionic segments of HSCR patients, offering a new target for their treatment using 5-HT agonists."

Journal • Pediatrics • Rare Diseases • RET

Prucalopride for Cognitive Functioning in Schizophrenia (clinicaltrials.gov) - P=N/A | N=34 | Not yet recruiting | Sponsor: University of Pittsburgh | Initiation date: Nov 2024 ➔ Feb 2025

Trial initiation date • CNS Disorders • Psychiatry • Schizophrenia

Efficacy and safety of prucalopride in patients with chronic idiopathic constipation stratified by age, body mass index, and renal function: a post hoc analysis of phase III and IV, randomized, placebo-controlled clinical studies. (PubMed, Therap Adv Gastroenterol) - P3, P4 | "No unexpected safety concerns were identified. ClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT01147926, NCT01424228, NCT01116206, NCT00483886, NCT00485940, NCT00488137."

Journal • P3 data • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder • Obesity • Renal Disease

Comparison of enteral prucalopride versus intravenous metoclopramide for feeding intolerance in patients with critical illness: a randomized double-blinded study. (PubMed, Front Pharmacol) - P1/2 | "The use of prucalopride was found to be tolerable and safe in critically ill patients. clinicaltrials.gov, identifier NCT05496179."

Journal

What Happens in Vagus: A Case Series of Three Pain-Predominant DGBI Managed With Transauricular Vagal Nerve Stimulation (ACG 2024) - "Dietary modification, metoclopramide, mirtazapine, cyproheptadine, pyridostigmine and omeprazole only led to partial improvement in symptoms of nausea and early satiety...She responded partially to duloxetine, pregabalin and CBT therapy...He had tried linaclotide, plecanatide, lubriprostone and prucalopride. Tenapanor was started, leading to improvement in constipation but abdominal pain persisted. Adjunct pharmacological neuromodulators like nortriptyline, duloxetine and gabapentin were not helpful...We share our stimulation parameters and outcomes (Table 1) in management of three pain-predominant DGBIs, including functional dyspepsia, centrally mediated abdominal pain syndrome, and pain-predominant IBS-C. Figure: Table 1: taVNS in DGBI - Parameters of Stimulation and Outcomes"

Clinical • Constipation • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Mood Disorders • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Psychiatry

Endoscopic Intraluminal Electrohydraulic Lithotripsy for the Treatment of a Giant Rectal Fecalith (ACG 2024) - "She was admitted to the hospital for bowel regimen prior to colonoscopy that included enemas, polyethylene glycol (PEG), senna and prucalopride...To prevent the development of serious complications, alternative endoscopic procedures, such as EHL, should be considered after conventional methods fail. Figure: Figure 1: A. Computed tomography of the abdomen and pelvis showing a 58 x 50 mm inspissated, calcified rectal fecal ball; B. Endoscopic image showing the large, calcified fecalith unable to be fragmented with polypectomy snare; C. Endoscopic image showing successful fragmentation of fecalith using electrohydraulic lithrotripsy (EHL) with over 2500 EHL pulses delivered via 2 lithotripsy probes."

CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Multiple Sclerosis

Idiopathic Chronic Intestinal Pseudo-Obstruction Treated With Small Intestinal Transplant (ACG 2024) - "There was no improvement after rifaximin for presumed small intestinal bacterial overgrowth...An NG tube was placed with persistent high output and symptoms despite trials of antiemetics, pyridostigmine, prucalopride, and decompressing GJ-tube...This is a unique case as it demonstrates the disease severity while highlighting the need for research on optimal surgical timing to initiate small bowel transplant evaluation for CIPO patients. Figure: Contrast-enhanced CT Abdomen/Pelvis demonstrating small bowel dilatation, multiple air-fluid levels, and small bowel wall thickening suggesting an obstructive process without mechanical obstruction"

Celiac Disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Pain • Transplantation

A Man With Paraneoplastic Gastrointestinal Dysmotility (ACG 2024) - "In our case the patient was treated with prucalopride and an aggressive osmotic laxative regimen with some clinical improvement...Figure: Figure 1. Endoscopy images"

Constipation • Gastrointestinal Cancer • Gastrointestinal Disorder • Lung Cancer • Oncology • Small Cell Lung Cancer

Genetic Gut Check: Atypical Gastroparesis in an Adult With 10p15.3 Microdeletion Syndrome (ACG 2024) - "Her symptoms were thought to be from GERD and treated over 4 months with escalating doses of omeprazole, with adjunctive famotidine added later, but without improvement...A trial of metoclopramide was unsuccessful. She was then switched to prucalopride which has significantly improved chest pain, emesis, and weight loss...Alternatively, some literature blames anatomic abnormalities that mask GI dysmotility. While further research is necessary to better understand 10p15.3 microdeletion syndrome's pathophysiology, we hope this case raises clinician awareness of atypical GI presentations in such patients and the importance of maintaining a broad differential."

Clinical • Cardiovascular • Celiac Disease • Developmental Disorders • Eosinophilic Esophagitis • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Mental Retardation • Pain • Pediatrics • SMYD3

The Serotonin 5-HT4 Agonist Prucalopride Attenuates Traumatic Brain Injury-Induced Neuroinflammation via the Gut-Brain Axis (ACS-CLINCON 2024) - "Treatment with a 5-HT4 agonist attenuates TBI-induced neuroinflammation, suggesting a novel approach to improve outcomes in patients with TBI by focusing on intestinal serotonin pathways."

CNS Disorders • Gastrointestinal Disorder • Inflammation • Inflammatory Bowel Disease • Vascular Neurology • CHGA • IL1B • TNFA

Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies. (PubMed, Neurobiol Pain) - "Six-hour treatment with the specific Gαs-coupled 5-HT4 receptor agonist, prucalopride, or with the adenylyl cyclase activator forskolin induced long-term hyperexcitability (LTH) in DRG neurons that manifested 12-24 h later as action potential (AP) discharge (ongoing activity, OA) during artificial depolarization to -45 mV, a membrane potential that is normally subthreshold for AP generation...However, the discovery that this prototypical memory induction pathway can induce nociceptor LTH, along with reports that cAMP signaling and CREB activity in DRGs can induce hyperalgesic priming, suggest that early, temporary, cAMP-induced transcriptional and translational mechanisms can induce nociceptor LTH that might last for long periods. The present results also raise the question of whether reactivation of primed signaling mechanisms by re-exposure to inflammatory mediators linked to cAMP synthesis during subsequent challenges to bodily integrity can..."

Journal • Pain

PASSING YOUR PATENCY TEST: DO PRUCALOPRIDE AND FASTING MAKE A DIFFERENCE? (UEGW 2024) - "This study shows that fasting improves patency tests pass rates, but Prucalopride does not. Fasting and subsequent patency capsule ingestion promoting the gastro-ileal reflex is a possible explanation. It is unclear in this study why Prucalopride, a prokinetic and laxative, failed to show an improvement in pass rates despite being shown to improve VCE completion rates in other studies."

Gastrointestinal Disorder

REAL-WORLD EXPERIENCE OF USING PRUCALOPRIDE FOR THE TREATMENT OF DYSPHAGIA IN PATIENTS WITH NEGATIVE GASTROSCOPY AND CHICAGO III OESOPHAGEAL DYSMOTILITY IN CLINICAL PRACTICE (UEGW 2024) - "Our study suggests Prucalopride might be a well-tolerated and useful treatment for dysphagia in patients with dysmotility disorders, mainly in the absence of pathological reflux. However, prospective randomized controlled studies are needed to confirm these data."

Clinical • Real-world • Real-world evidence • Constipation • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Pain

A real-world study of persistence and adherence to prescription medications in patients with chronic idiopathic constipation in the United States. (PubMed, J Manag Care Spec Pharm) - "Inclusion criteria were patients (aged ≥18 years) with at least 1 prescription fill for prucalopride, lubiprostone, linaclotide, or plecanatide on or after April 2, 2019 (commercial availability of prucalopride), and at least 1 constipation-related diagnosis code. The findings of this study indicate that prucalopride has higher treatment persistence and adherence compared with other CIC prescription medications. This research represents the first instance of a real-world claims study showcasing such outcomes."

Adherence • Journal • Observational data • Real-world • Real-world evidence • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder

Enhanced Intestinal Recovery and Reduced Inflammation with Prucalopride Succinate in Minimally Invasive Gastrectomy: A Randomized Clinical Trial (KINGCA Week 2024) - No abstract available

Clinical • Inflammation

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

Prucalopride for Cognitive Functioning in Schizophrenia (clinicaltrials.gov) - P=N/A | N=34 | Not yet recruiting | Sponsor: University of Pittsburgh | Trial completion date: Sep 2025 ➔ Dec 2025 | Initiation date: Aug 2024 ➔ Nov 2024 | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

The impact of long-course chemoradiotherapy on the myenteric plexus, neuromuscular functions and responses to prokinetic drugs in the human rectum. (PubMed, United European Gastroenterol J) - "Several months after chemoradiotherapy, the rectum was not inflamed and myenteric neuron numbers/phenotype unchanged. However, nitrergic activity was increased relative to cholinergic activity, and prokinetic-like drug activity was lost or greatly reduced. Thus, chemoradiotherapy causes long-term changes in neuromuscular functions and markedly reduces the efficacy of drugs for treating constipation."

Journal • Colorectal Cancer • Constipation • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • PTPRC

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial. (PubMed, Br J Psychiatry) - "These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting."

Journal • CNS Disorders • Constipation • Depression • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry

RISK OF CONSTIPATION WITH ANTI-OBESITY MEDICATION AND CURRENT PRESCRIBING PATTERN LANDSCAPE IN MANAGING THE SIDE EFFECT (DDW 2024) - "We then determined whether these patients were prescribed a medication for constipation (plecanatide linaclotide tegaserod lubiprostone polyethylene glycol (PEG) magnesium oxide lactulose bisacodyl senna sodium picosulfate tenapanor prucalopride)...8% (7/145) diethylpropion...Liraglutide and phentermine-topiramate had the highest constipation rates. Black patients had higher rate of new constipation diagnosis and treatment compared to White patients. Semaglutide had the least risk for requiring constipation medication."

Adverse events • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity

IMPLICATIONS OF POPULAR TRENDING ANTI-OBESITY MEDICATIONS - AN INCREASE IN HEALTHCARE COST AND UTILIZATION FOR THE POPULATION WITH CONSTIPATION (DDW 2024) - "Inclusion criteria included obese patients started on an AOM (per the 0 AGA Guideline on the Pharmacological Interventions for Adults with Obesity - semaglutide liraglutide phentermine-topiramate phentermine naltrexone-bupropion diethylpropion) who subsequently developed constipation after one week to twelve months after starting the AOM...The search was then narrowed to patients who were prescribed a constipation medication: plecanatide linaclotide tegaserod lubiprostone polyethylene glycol (PEG) magnesium oxide lactulose bisacodyl senna sodium picosulfate tenapanor prucalopride...Patients on AOM who develop constipation appear to have a threefold increase in ED visits and inpatient admissions. The average annual cost of constipation medication alone is $5 485. 04 per person."

Clinical • HEOR • Constipation • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity

Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies. (PubMed, bioRxiv) - "Six-hour treatment with the specific Gαs-coupled 5-HT4 receptor agonist, prucalopride, or with the adenylyl cyclase activator, forskolin, induced long-term hyperexcitability (LTH) in DRG neurons that manifested 12-24 hours later as action potential (AP) discharge (ongoing activity, OA) during artificial depolarization to -45 mV, a membrane potential that is normally subthreshold for AP generation...An interesting possibility is that these mechanisms can also be reactivated by re-exposure to inflammatory mediators such as serotonin during subsequent challenges to bodily integrity, "reconsolidating" the cellular memory and thereby extending the duration of persistent nociceptor hyperexcitability. Nociceptor long-term hyperexcitability (LTH) can be induced by a 5-HT4R agonist.5-HT4R-induced LTH manifests as ongoing activity during modest depolarization.Enhanced ongoing activity is associated with long-term potentiation of DSFs.Induction of LTH depends upon PKA,..."

Journal • Pain