Oral prolonged‐release oxycodone/naloxone for managing pain and opioid‐induced constipation: a review of the evidence

Background: Opioids provide effective relief from moderate‐to‐severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed‐dose oxycodone/naloxone prolonged‐release tablets (OXN PR) were designed to address the opioid class effect of opioid‐induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse‐deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone. Methods: A literature search was conducted to assess the evidence base for OXN PR to treat moderate‐to‐severe pain and its impact on bowel function, based on published clinical trials and observational studies. Results: Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate‐to‐severe cancer‐related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease–related pain. No unanticipated safety concerns have been reported in elderly patients. Conclusions: Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate‐to‐severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day)

Gastric electrical stimulation is safe during pregnancy and delivery: Results from a French cohort

Abstract Background Gastric electrical stimulation (GES) is an effective therapy in medically refractory chronic nausea and vomiting. GES is assumed to be a contraindication for pregnancy. We examined the safety of GES during pregnancy and its clinical impact on vomiting symptoms. Methods A retrospective study was performed in two tertiary centers including all female patients of childbearing age implanted with GES. Patients without pregnancy while on GES were asked about their desire and concerns about pregnancy. Patients who were pregnant while on GES therapy were interviewed about the course of the pregnancy and labor, as well as the health of the children. Key Results Among 91 patients implanted at childbearing age, 54 patients without pregnancy answered the questionnaire. Nine patients (16.7%) reported a desire for pregnancy and five patients (7.4%) reported worries about the safety of GES during pregnancy. Sixteen pregnancies were reported in 10 patients. All pregnancies ended in a live birth with premature birth in 12 pregnancies (75.0%). No health concern was currently noted in these children. No severe GES‐related complications occurred during pregnancy with only pain at the implantation site reported during 3 pregnancies (18.8%). The severity and frequency of nausea and vomiting significantly increased during the first trimester ( p = 0.04 and p = 0.005, respectively) and decreased after the delivery, becoming lower than before the pregnancy ( p = 0.044 and p = 0.011, respectively). Conclusion & Inferences Patients are concerned regarding pregnancy while being treated with GES. No serious maternal or fetal complications related to GES were noted in our cohort

Racecadotril Efficacy in the Symptomatic Treatment of Adult Acute Diarrhoea: A Systematic Review and Meta-Analysis

The efficacy of racecadotril (RC), an intestinal antisecretory drug acting via an enkephalinase inhibition, was reviewed in paediatric acute diarrhoea but not yet in adults. Objective: To estimate the effectiveness of RC in the symptomatic treatment of acute diarrhoea in adults. Data Sources: A systematic review of MedLine, Cochrane Controlled Trials Register, DARE, and Embase (up to November 2013). Additional studies were identified by contacting clinical experts and the manufacturer. Study Selection and Appraisal: Randomized Controlled Trials performed in adults suffering from acute diarrhoea using RC in one treatment arm. Independent extraction of articles using predefined data fields, and methodological quality measurement assessment. All randomised trials performed in adults suffering from acute diarrhoea with RC as the studied group. Statistics: The main efficacy endpoint was diarrhoea duration defined as time to recovery compared between groups by survival techniques and converted into hazard ratio (HR). We exclusively used a random-effect meta-analytic model. Constipation proportion was the main safety endpoint, evaluated between treatments by the Relative Risks (RR). Results: Twelve randomised trials (2619 patients) met inclusion criteria. Duration of diarrhoea was much shorter in the RC group, the proportion of patients having recovered at any time of the treatment period was 65% higher in the RC group, compared with placebo (HR = 1.65 [1.38 - 1.97], p < 0.00001, n= 1001). Duration of diarrhoea was similar in the RC and loperamide groups (HR = 1.08 [0.95 - 1.22], p = 0.24, n = 1618). The proportions of constipated patients were similar in the RC and placebo groups 0.95 [0.24 - 3.68], p = 0.97), however, about 3 times more constipated patients were found in the loperamide group compared with the RC group (RR = 0.34 [0.22 - 0.51], p < 0.0001)

Racecadotril in the Treatment of Acute Diarrhoea in Adults. An Individual Patient Data Based Meta-Analysis

Racecadotril is an antidiarrhoeal drug with a pure intestinal antisecretory mechanism of action. Aim: To assess racecadotril efficacy, whatever its dose, versus placebo in adult acute diarrhoea. Methods: Individual Patient Data meta-analysis following multilevel mixed models testing of the significance of the treatment effect adjusted for baseline covariates. Diarrhoea duration was the common main criteria. Results: Four randomized clinical trials (n = 669) were identified with raw data. The clinical global impression evaluated at baseline by the physician was found to be the essential predictor influencing the outcome. As compared to placebo, the 100 mg dose, the minimum effective dose, induced a 80% increase of the recovered patient proportion at anytime (Hazard Ratio = 1.8 [1.3, 2.5], p < 0.001), a 60% increase of the responder proportion i.e. recovery within 3 days (p < 0.001), a 47% reduction of abdominal pain and nausea and an overall 33% decrease of sick days (p < 0.001). In conclusion, as compared to placebo, racecadotril induced several significant effects, such as reducing the diarrhoea duration, the number of stools and associated symptoms, leading to less lost productivity

Oral Prolonged-Release Oxycodone/Naloxone for Managing Pain and Opioid-Induced Constipation: A Review of the Evidence

Opioids provide effective relief from moderate-to-severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed-dose oxycodone/naloxone prolonged-release tablets (OXN PR) were designed to address the opioid class effect of opioid-induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse-deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone.status: accepte

Maintenance of a Gastric Pacemaker in the Excluded Stomach During a Roux-en-Y Gastric Bypass Procedure in a Patient with Obesity, Type 1 Diabetes and Refractory Gastroparesis

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Functional Digestive Symptoms and Quality of Life in Patients with Ehlers-Danlos Syndromes: Results of a National Cohort Study on 134 Patients

<div><p>Background and Objectives</p><p>Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders. Gastrointestinal manifestations in EDS have been described but their frequency, nature and impact are poorly known. We aimed to assess digestive features in a national cohort of EDS patients.</p> <p>Methods</p><p>A questionnaire has been sent to 212 EDS patients through the French patient support group, all of which had been formally diagnosed according to the Villefranche criteria. The questionnaire included questions about digestive functional symptoms, the GIQLI (Gastrointestinal Quality of Life Index), KESS scoring system and the Rome III criteria.</p> <p>Results</p><p>Overall, 135 patients (64% response rate) completed the questionnaire and 134 were analyzable (123 women; 91%). Mean age and Body Mass Index were respectively 35±14.7 years and 24.3±6.1 kg/m². The most common EDS subtype was hypermobility form (n=108; 80.6%). GIQLI and KESS median values were respectively 63.5 (27-117) and 19 [13.5-22]. Eighty four percent of patients had functional bowel disorders (FBD) according to the Rome III criteria. An irritable bowel syndrome according to the same criteria was observed in 64 patients (48%) and 48 patients (36%) reported functional constipation. A gastro-esophageal reflux disease (GERD) was reported in 90 patients (68.7%), significantly associated with a poorer GIQLI (60.5±16.8 <i>versus</i> 75.9±20.3; p<0.0001). GIQLI was also negatively impacted by the presence of an irritable bowel syndrome or functional constipation (p=0.007). There was a significant correlation between FBD and GERD.</p> <p>Conclusions</p><p>Natural frequency of gastrointestinal manifestations in EDS seems higher than previously assessed. FBD and GERD are very common in our study population, the largest ever published until now. Their impact is herein shown to be important. A systematic clinical assessment of digestive features should be recommended in EDS.</p> </div

GIQLI score (individual spot and means) according to the presence of Ehlers-Danlos syndrome.

<p>GIQLI score (individual spot and means) according to the presence of Ehlers-Danlos syndrome.</p

Subscales of the GIQLI between patients with EDS (box with white lines) and control population (filled box) and results of the Student comparison.

<p>Subscales of the GIQLI between patients with EDS (box with white lines) and control population (filled box) and results of the Student comparison.</p

Flow Chart of the functional bowel disorders among the population of Ehlers-Danlos syndrome.

<p>Flow Chart of the functional bowel disorders among the population of Ehlers-Danlos syndrome.</p