dexlansoprazole and Gastroesophageal-Reflux

The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease.. We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score.. We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated.. Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.

Topics: Adult; Alginates; Dexlansoprazole; Endoscopy, Gastrointestinal; Gastroesophageal Reflux; Gastrointestinal Agents; Heartburn; Humans; Network Meta-Analysis; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome

Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anticoagulants; Asia, Eastern; Asian People; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Dexlansoprazole; Drug Interactions; Drug Therapy, Combination; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Humans; Isoenzymes; Pantoprazole; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Proton Pump Inhibitors; Rabeprazole; Ticlopidine

The prevalence of gastroesophageal reflux disease continues to increase with the aging population and the obesity epidemic. Therapeutic failures can have significant detrimental effects in patients. Recently, dexlansoprazole MR and esomeprazole strontium were introduced to the class of proton pump inhibitors (PPIs).. This article will review the pharmacodynamics and pharmacokinetics of dexlansoprazole MR and esomeprazole strontium. Using the keywords 'dexlansoprazole MR' and 'esomeprazole strontium' in the search engines of PubMed, Cochrane Reviews and Google, we were able to identify peer-reviewed publications, abstracts and presentations at national society educations meetings and present a balanced view of the available data.. Dexlansoprazole MR and esomeprazole strontium offer an innovative delivery mechanism compared to conventional PPIs. Further trials are necessary in order to establish superiority.

Topics: Administration, Oral; Animals; Clinical Trials as Topic; Dexlansoprazole; Drug Evaluation, Preclinical; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Treatment Outcome

Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a novel system, the dual delayed release formulation. The drug has been shown to be efficacious in healing erosive esophagitis as compared with lansoprazole. When compared to placebo, dexlansoprazole provided significantly higher maintenance rates for healed esophageal mucosa in patients with erosive esophagitis and symptom control in patients with non-erosive reflux disease. Dexlansoprazole could be taken without regard to food. Overall, dexlansoprazole is well tolerated and has a comparable side-effect profile to lansoprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Delayed-Action Preparations; Dexlansoprazole; Esophagitis; Gastroesophageal Reflux; Humans; Lansoprazole; Mucous Membrane; Proton Pump Inhibitors; Stereoisomerism

Dexlansoprazole modified release (MR; Dexilant™), the R-enantiomer of lansoprazole, was approved in the USA in 2009 for the management of erosive esophagitis and nonerosive reflux disease. Dexlansoprazole MR has a unique dual delayed-release delivery system that was designed to address unmet needs that may accompany the use of single-release proton pump inhibitors (PPIs), specifically, their short plasma half-life and requirement for meal-associated dosing. The delivery technology of dexlansoprazole MR is designed to release the drug in two separate pH-dependent phases, the first in the proximal duodenum and the second in the more distal small intestine. This extends plasma concentration and pharmacodynamic effects of dexlansoprazole MR beyond those of single-release PPIs and allows for dosing at any time of the day without regard to meals. This added convenience, along with excellent healing of esophagitis and symptom relief, substantiate its use in patients with gastroesophageal reflux disease requiring PPI treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Delayed-Action Preparations; Dexlansoprazole; Esophagitis; Gastroesophageal Reflux; Humans; Lansoprazole; Treatment Outcome; United States

To describe the pharmacology, pharmacokinetics, and efficacy of dexlansoprazole in the treatment of heartburn associated with nonerosive gastroesophageal reflux disease (GERD) and healing and maintenance of healing of all grades of erosive esophagitis (EE).. Literature searches were conducted using MEDLINE Ovid (1950-December 2009, week 4) and EMBASE (1980-2009, week 53) using the term dexlansoprazole. References from articles obtained from the search were evaluated for other relevant citations.. All articles published in English evaluating the pharmacology, pharmacokinetics, efficacy, and adverse effect profile of dexlansoprazole were selected for inclusion.. Dexlansoprazole is the newest addition to the proton pump inhibitor (PPI) class and is approved for the treatment of heartburn associated with nonerosive GERD, healing of all grades of EE, as well as maintenance of healing of EE. Dexlansoprazole has a unique dual delayed-release formulation, which releases drug at 2 points in time; the first peak occurs 1-2 hours after administration and the second occurs within 4-5 hours after administration. In Phase 3 trials conducted in adults, researchers found that dexlansoprazole increases rates of healing of EE, as well as the maintenance of healing, compared to lansoprazole. Relief of heartburn symptoms was comparable among the dexlansoprazole and lansoprazole treatment groups. Common adverse effects of dexlansoprazole are similar to those of the other PPIs, including diarrhea, abdominal pain, nausea, upper respiratory infection, vomiting, and flatulence.. Dexlansoprazole provides another treatment option for the management of EE and symptoms of heartburn. Considering that the cost of dexlansoprazole is not favorable, further studies evaluating potential advantages over other agents are necessary to define the role of dexlansoprazole in the treatment of these conditions.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Dexlansoprazole; Drug Interactions; Esophagitis; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Treatment Outcome

Dexlansoprazole modified release (dexlansoprazole MR) is an orally administered delayed-release formulation of the R-enantiomer of the proton pump inhibitor lansoprazole that is effective in improving the healing of all grades of erosive oesophagitis, maintaining the healing of erosive oesophagitis and in the treatment of symptomatic non-erosive reflux disease (NERD). In two large, identical, 8-week, randomized, double-blind, multicentre phase III trials, dexlansoprazole MR 60 mg once daily achieved complete healing in >or=92% of patients with all grades of erosive oesophagitis (primary endpoint) and was noninferior to lansoprazole 30 mg once daily using life-table analysis. Moreover, in a randomized, double-blind, multicentre phase III trial in patients with healed erosive oesophagitis, dexlansoprazole MR 30 mg once daily was significantly more effective than placebo in maintaining healing following 6 months' treatment (primary endpoint). In addition, the proportion of 24-hour heartburn-free days (primary endpoint) was significantly greater in recipients of dexlansoprazole MR 30 mg once daily than in recipients of placebo following 4 weeks' treatment in a large, randomized, double-blind, multicentre phase III trial in patients with NERD. Dexlansoprazole MR 30 or 60 mg once daily was generally well tolerated in a pooled analysis of clinical trials of up to 12 months' duration.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Delayed-Action Preparations; Dexlansoprazole; Esophagitis; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors

Dexlansoprazole, the dextrorotatory enantiomer of lansoprazole, is a proton pump inhibitor (PPI) formulated to have dual delayed-release properties. It is indicated for healing all grades of esophagitis, maintaining the healing of erosive esophagitis (EE), and treating heartburn associated with nonerosive gastroesophageal reflux disease.. This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of dexlansoprazole, as well as its clinical efficacy and tolerability.. MEDLINE (1966-April 2010) and International Pharmaceutical Abstracts (1970-April 2010) were searched for original research and review articles published in English using the terms dexlansoprazole and TAK-390MR. The reference lists of identified articles were reviewed for additional pertinent publications. Abstracts from 2007-2009 American College of Gastroenterology and Digestive Disease Week meetings were searched using the same terms.. By irreversibly binding to H(+)K(+)-ATPase, dexlansoprazole inhibits acid production by the parietal cell. Its dual delayed-release formulation provides 2 distinct releases of medication, prolonging the mean residence time compared with lansoprazole (5.56-6.43 vs 2.83-3.23 hours, respectively). In 2 identical Phase III trials of the healing of EE, there were no significant differences in rates of complete healing after 8 weeks between dexlansoprazole 60 and 90 mg once daily and lansoprazole 30 mg once daily. In 2 studies of the maintenance of healing of EE, rates of healing at 6 months were significantly higher with dexlansoprazole 30, 60, and 90 mg once daily compared with placebo (P < 0.001). Patients with nonerosive reflux disease who received dexlansoprazole 30 or 60 mg once daily had significantly more 24-hour heartburn-free days compared with those who received placebo (P < 0.001). Dexlansoprazole was well tolerated compared with placebo or lansoprazole in all studies.. In the studies reviewed, dexlansoprazole was well tolerated and effective in the healing and maintenance of EE, and in the treatment of nonerosive reflux disease. However, most of the available evidence involved comparisons with placebo, making it difficult to draw meaningful conclusions about the place of dexlansoprazole among PPIs. More head-to-head comparative trials with other PPIs are needed to determine whether the unique formulation of dexlansoprazole translates into a clinically meaningful improvement in outcomes.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Delayed-Action Preparations; Dexlansoprazole; Esophagitis; Gastroesophageal Reflux; Heartburn; Humans; Lansoprazole; Proton Pump Inhibitors; Treatment Outcome

Proton pump inhibitors (PPIs) have been used for more than two decades to control symptoms of gastroesophageal illnesses. Studies have shown that most PPIs do not provide 24-h symptom control, and that can be the reason for treatment failure. Recently, dexlansoprazole dual delayed release (DDR) (Takeda Pharmaceuticals North America, Inc., USA) under the trade name of Kapidex (Takeda Pharmaceutical Company Limited, Japan) came onto the market to provide longer duration of action and more effective acid suppression.. The purpose of this paper is to discuss the pharmacology of dexlansoprazole DDR and to provide a concise review of all available studies showing its efficacy. The combination of the slower metabolism of the R-enantiomer and novel dual release pharmacokinetics is impressive.. This manuscript is based on a review of all currently available medical literature on dexlansoprazole DDR.. Dexlansoprazole DDR has the potential to outperform traditional PPIs based on the metabolism and novel pharmacokinetics. It is currently FDA approved for the treatment of erosive esophagitis (acute, maintenance) and symptomatic gastroesophageal reflux disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acute Disease; Anti-Ulcer Agents; Delayed-Action Preparations; Dexlansoprazole; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Treatment Outcome

The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD).. Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups.. There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all < 0.05 by intention-to-treat). Multivariate logistic regression analysis showed that the use of dexlansoprazole, presence of dyslipidemia, and typical GERD symptoms (acid reflux and heartburn) were predictors for symptom response for cough; the use of dexlansoprazole and presence of erosive esophagitis were predictors for symptom response for globus (P all < 0.05). No predictor for therapy response to hoarseness was noted.. There is a higher response rate for cough and globus symptoms in patients with atypical GERD after the 8-week PPI therapy with dexlansoprazole rather than lansoprazole.

Topics: Aged; Cough; Dexlansoprazole; Dyslipidemias; Esophagitis; Female; Gastroesophageal Reflux; Globus Sensation; Hoarseness; Humans; Lansoprazole; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Time Factors; Treatment Outcome

In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump inhibitor, dexlansoprazole, is approved for healing EE of all grades, maintenance of healed EE, relief of heartburn, and treatment of symptomatic non-erosive GERD in patients ≥ 12 years.. To assess safety and efficacy of dexlansoprazole dual delayed-release capsule in healing of EE and maintenance of healed EE in adolescents.. A multicenter, phase 2, 36-week study was conducted in 62 adolescents (12-17 years) with endoscopically confirmed EE. Patients received dexlansoprazole 60 mg once daily (QD) during open-label healing phase. Those with confirmed healing at week 8 were randomized to dexlansoprazole 30 mg QD or placebo during 16-week, double-blind maintenance phase, with subsequent treatment-free follow-up of ≥ 12 weeks. Primary endpoints were treatment-emergent adverse events (TEAEs) in ≥ 5% of patients during treatment. Secondary endpoints included percentages of patients with healing of EE and with maintenance of healed EE.. 88% of patients achieved EE healing, and 61.3% reported a TEAE [headache (12.9%), oropharyngeal pain (8.1%), diarrhea (6.5%), and nasopharyngitis (6.5%)]. During maintenance phase, healing was maintained in 82% and 58% of dexlansoprazole and placebo groups, respectively. 72.0% of dexlansoprazole-treated patients reported TEAEs, which included headache (24.0%), abdominal pain (12.0%), nasopharyngitis (12.0%), pharyngitis (12.0%), sinusitis (12.0%), bronchitis (8.0%), upper respiratory tract infection (8.0%), and insomnia (8.0%); 61.5% experienced a TEAE with placebo.. Dexlansoprazole is safe and efficacious for healing EE and maintenance of healed EE in adolescents.

Topics: Abdominal Pain; Adolescent; Child; Delayed-Action Preparations; Dexlansoprazole; Diarrhea; Double-Blind Method; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Headache; Humans; Maintenance Chemotherapy; Male; Nasopharyngitis; Oropharynx; Pain; Pharyngitis; Proton Pump Inhibitors; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Proton pump inhibitors are effective at reducing heartburn. No studies have evaluated their efficacy in Ramadan. Dexlansoprazole has a unique active formulation independent of time-of-day dosing or food. The aim is to investigate the efficacy of dexlansoprazole 60 mg during Ramadan in patients with symptomatic heartburn.. Subjects recruited using poster, radio, and SMS advertisements completed a diary using a mobile-friendly application and received daily SMS reminders. Dexlansoprazole was started on day 8 for 3 weeks. No placebo arm was used in this trial. Primary endpoint was relief of heartburn expressed as mean 24-h free heartburn percentage (24FH%) per weekly period.. A total of 32 patients were enrolled. During week 1, only 1 person (3.1%) was heartburn-free and mean 24FH% was 41.1 ± 24.8%. On dexlansoprazole, mean 24FH% rose to 63.4 ± 23.8 and 81.6 ± 24.5% in weeks 2 and 4, respectively (p < 0.001 for both). Median 24FH% increased from 35.7% in week 1 to 71.4 and 85.7% in weeks 2 and 4, respectively. Mean Gastroesophageal Reflux Disease Questionnaire (GERDQ) scores decreased from 10.0 ± 3.2 in week 1 to 6.53 ± 2.2 in week 2 (p < 0.001) and 5.87 ± 2.1 in week 4 (p < 0.001). Mean heartburn severity score decreased from 2.5 ± 1.0 to 1.7 ± 0.8 (p = 0.001). Early response was higher in patients with GERDQ scores ≥8 (p = 0.012).. Dexlansoprazole is effective in the treatment of heartburn during Ramadan. Clinicaltrials.gov number: NCT03079050.

Topics: Adult; Dexlansoprazole; Fasting; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Proton Pump Inhibitors; Religion; Surveys and Questionnaires; Treatment Outcome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dexlansoprazole; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Severity of Illness Index; Structure-Activity Relationship; Time Factors; Young Adult

Proton pump inhibitors are commonly used to treat gastro-esophageal reflux disease (GERD) and nonerosive GERD (NERD) in adolescents and adults. Despite the efficacy of available medications, many patients have persisting symptoms, indicating a need for more effective agents.. To assess the safety and efficacy of dexlansoprazole dual delayed-release capsules in adolescents for treatment of symptomatic NERD.. A phase 2, open-label, multicenter study was conducted in adolescents aged 12-17 years. After a 21-day screening period, adolescents with endoscopically confirmed NERD received a daily dose of 30-mg dexlansoprazole for 4 weeks. The primary endpoint was treatment-emergent adverse events (TEAEs) experienced by ≥5% of patients. The secondary endpoint was the percentage of days with neither daytime nor nighttime heartburn. Heartburn symptoms and severity were recorded daily in patient electronic diaries and independently assessed by the investigator, along with patient-reported quality of life, at the beginning and end of the study.. Diarrhea and headache were the only TEAEs reported by ≥5% of patients. Dexlansoprazole-treated patients (N = 104) reported a median 47.3% of days with neither daytime nor nighttime heartburn. Symptoms such as epigastric pain, acid regurgitation, and heartburn improved in severity for 73-80% of patients. Pediatric Gastroesophageal Symptom and Quality of Life Questionnaire-Adolescents-Short Form symptom and impact subscale scores (scaled 1-5) each decreased by an average of 0.7 units at week 4.. Use of 30-mg dexlansoprazole in adolescent NERD was generally well tolerated and had beneficial effects on improving heartburn symptoms and quality of life.. This study has the ClinicalTrials.gov identifier NCT01642602.

Topics: Administration, Oral; Adolescent; Age of Onset; Capsules; Child; Delayed-Action Preparations; Dexlansoprazole; Europe; Female; Gastroesophageal Reflux; Heartburn; Humans; Latin America; Male; North America; Proton Pump Inhibitors; Quality of Life; Remission Induction; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome

To compare the one-week clinical effects of single doses of dexlansoprazole and esomeprazole on grades A and B erosive esophagitis.. We enrolled 175 adult patients with gastroesophageal reflux disease (GERD). The patients were randomized in a 1:1 ratio into two sequence groups to define the order in which they received single doses of dexlansoprazole (. Thirteen patients were lost to follow-up, resulting in 81 patients in each group for the per-protocol analysis. The CSRs for both groups were similar at days 1, 3 and 7. In the subgroup analysis, the female patients achieved higher CSRs in the dexlansoprazole group than in the esomeprazole group at day 3 (38.3%. The overall CSR for GERD patients was similar at days 1-7 for both the dexlansoprazole and esomeprazole groups, although a higher incidence of CSR was observed on day 3 in female patients who received a single dose of dexlansoprazole.

Topics: Adult; Dexlansoprazole; Esomeprazole; Esophagitis, Peptic; Feeding Behavior; Female; Gastroesophageal Reflux; Humans; Intention to Treat Analysis; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors; Sex Factors; Treatment Outcome

Gastro-oesophageal reflux disease (GERD) is characterised by symptomatic heartburn and regurgitation. Treatment with proton pump inhibitors (PPI) effectively decreases heartburn symptoms, but their effects on symptomatic regurgitation are less clear.. To determine the impact of PPI therapy on heartburn and regurgitation severity in patients with either non-erosive GERD (NERD) or erosive oesophagitis (EE).. Endoscopically-confirmed NERD patients received dexlansoprazole 30 or 60 mg or placebo in a randomised, blinded, 4-week study. Endoscopically-confirmed EE patients received dexlansoprazole 60 mg or lansoprazole 30 mg in two 8-week, randomised, blinded healing studies. The Patient Assessment of Upper Gastrointestinal Symptom Severity questionnaire, which includes a heartburn/regurgitation subscale, was administered to assess symptom severity at baseline, and at weeks 2 and 4 of the NERD study and at weeks 4 and 8 during the EE trials. We defined separate subscales for heartburn and regurgitation for this post-hoc analysis. Among patients with both symptoms at baseline, improvements in individual heartburn and regurgitation subscales along with the original combined heartburn/regurgitation subscale were determined.. In the NERD and EE studies, 661 and 1909 patients, respectively, had both heartburn and regurgitation at baseline. NERD patients receiving dexlansoprazole 30 and 60 mg experienced significantly greater improvements in symptom severity for both heartburn and regurgitation compared with placebo. EE patients receiving dexlansoprazole 60 mg had significantly greater improvements in heartburn/regurgitation and heartburn-only subscales at week 4 compared with those receiving lansoprazole.. Dexlansoprazole appears to be effective in improving both heartburn and regurgitation, and this improvement is maintained for the duration of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dexlansoprazole; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis; Female; Gastroesophageal Reflux; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Young Adult

Dexlansoprazole MR 30  mg once daily (QD) is approved in adults for the treatment of symptomatic nonerosive gastroesophageal reflux disease (GERD) and maintenance of healed erosive esophagitis (EE); 60  mg is approved for healing EE. The present study assesses the pharmacokinetic (PK) profile and safety of dexlansoprazole MR in adolescent patients.. Phase 1, open-label, parallel-group, multicenter study in male and female adolescents (12-17 years) with GERD. Patients were randomized to receive dexlansoprazole MR (30 or 60  mg, QD) for 7 days. Blood samples to determine dexlansoprazole plasma concentrations were drawn over a 24-hour period after dosing on day 7. Dexlansoprazole plasma concentrations and PK parameters were summarized by dose group. Safety assessments included monitoring of adverse events (AEs).. Thirty-six patients (mean age 14.6 years), 14 boys and 22 girls, were randomized, with PK data available for 35 patients. The overall exposure of dexlansoprazole after administration of the 60-mg capsule was slightly less than double the exposure from the 30-mg capsule. Cmax (691 and 1136  ng/mL) and area under the plasma concentration time curve (2886 and 5120  ng · h/mL) values for the 30- and 60-mg doses, respectively, were similar to results from previous phase 1 studies in healthy adults. Twelve of 36 patients (33.3%) experienced a total of 21 treatment-emergent AEs. All of the AEs were considered to be of mild severity.. The PK data for dexlansoprazole MR 30- and 60-mg capsules in adolescent patients with symptomatic GERD were similar to those in healthy adults. Both doses were well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Area Under Curve; Child; Dexlansoprazole; Esophagitis; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Proton Pump Inhibitors

Many patients with gastroesophageal reflux disease (GERD) take a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily dexlansoprazole modified release (MR) has a dual-delayed release formulation, making it attractive for step-down management of patients whose symptoms are well controlled on twice-daily PPIs. We investigated whether step-down to once-daily dexlansoprazole controls heartburn in patients with GERD who were receiving twice-daily PPI therapy.. Patients 18 years and older taking a twice-daily PPI for symptom control were enrolled (n = 178) in a single-blind, multicenter study; 163 patients completed the study and 142 patients met criteria for the efficacy analysis. During the 6-week screening and treatment periods, patients recorded the presence of heartburn symptoms twice daily in electronic diaries. Patients' heartburn was considered well controlled if they had an average of 1 symptom or fewer per week during the last 4 weeks of screening and treatment. After screening, qualified patients were switched to masked dexlansoprazole MR 30 mg and placebo for 6 weeks. The primary efficacy end point was the proportion of patients whose heartburn remained well controlled after step-down. GERD-related symptoms and quality of life (QOL) also were evaluated using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the PAGI-QOL questionnaires, respectively.. After step-down to once-daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of patients (125 of 142). These patients were able to maintain their GERD-related symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI-QOL total and subscale scores, respectively.. Most patients with GERD who take twice-daily PPI to control heartburn are able to successfully step down to once-daily dexlansoprazole 30 mg.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Dexlansoprazole; Female; Gastroesophageal Reflux; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Quality of Life; Single-Blind Method; Treatment Outcome; Young Adult

Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression.. To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD).. In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs).. Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed.. Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190).

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Delayed-Action Preparations; Dexlansoprazole; Dose-Response Relationship, Drug; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Statistics as Topic; Time Factors; Treatment Outcome; Young Adult

Nocturnal heartburn and related sleep disturbances are common among patients with gastroesophageal reflux disease (GERD). This study evaluated the efficacy of dexlansoprazole MR 30 mg in relieving nocturnal heartburn and GERD-related sleep disturbances, improving work productivity, and decreasing nocturnal symptom severity in patients with symptomatic GERD.. Patients (N=305) with frequent, moderate-to-very severe nocturnal heartburn and associated sleep disturbances were randomized 1:1 in a double-blind fashion to receive dexlansoprazole MR or placebo once daily for 4 weeks. The primary end point was the percentage of nights without heartburn. Secondary end points were the percentage of patients with relief of nocturnal heartburn and of GERD-related sleep disturbances over the last 7 days of treatment. At baseline and week 4/final visit, patients completed questionnaires that assessed sleep quality, work productivity, and the severity and impact of nocturnal GERD symptoms.. Dexlansoprazole MR 30 mg (n=152) was superior to placebo (n=153) in median percentage of nights without heartburn (73.1 vs. 35.7%, respectively; P<0.001). Dexlansoprazole MR was significantly better than placebo in percentage of patients with relief of nocturnal heartburn and GERD-related sleep disturbances (47.5 vs. 19.6%, 69.7 vs. 47.9%, respectively; P<0.001), and led to significantly greater improvements in sleep quality and work productivity and decreased nocturnal symptom severity. Adverse events were similar across treatment groups.. In patients with symptomatic GERD, dexlansoprazole MR 30 mg is significantly more efficacious than placebo in providing relief from nocturnal heartburn, in reducing GERD-related sleep disturbances and the consequent impairments in work productivity, and in improving sleep quality/quality of life.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Dexlansoprazole; Double-Blind Method; Drug Administration Schedule; Efficiency; Female; Gastroesophageal Reflux; Health Status; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Quality of Life; Risk Factors; Severity of Illness Index; Sleep Wake Disorders; Surveys and Questionnaires; Treatment Outcome

Lansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus.. 24 recipients who were CYP2C19 EMs were studied.. Oral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured.. Pretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes.. (R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Alleles; Anti-Ulcer Agents; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Asian People; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 CYP2C19; Dexlansoprazole; Female; Gastroesophageal Reflux; Genotype; Half-Life; Humans; Immunosuppressive Agents; Japan; Kidney Transplantation; Lansoprazole; Male; Middle Aged; Mixed Function Oxygenases; Organic Anion Transporters; Polymorphism, Genetic; Tacrolimus

Topics: Dexlansoprazole; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors

Nocturnal acid breakthrough (NAB) may differ based on duration of proton pump inhibitor (PPI) action and Helicobacter pylori (H. pylori) infection; NAB may influence esophageal acidification (EA) and mucosal damage. Dexlansoprazole, a long-acting PPI, was not compared with omeprazole for NAB, gastric acid suppression, and EA in relation to H. pylori infection.. In this prospective open-label comparative observational study, gastroesophageal reflux disease (GERD) patients were evaluated using 24-h dual-channel pH-impedance monitoring while on dexlansoprazole (60 mg, n = 39) and omeprazole (20 mg, n = 41) to study the degree of gastric acid suppression, esophageal acid exposure, and NAB (primary outcome measures). H. pylori was detected by rapid urease test and histology.. NAB tended to be frequent with omeprazole than dexlansoprazole (33/41 [80.5%] vs. 23/39 [59%]; p = 0.06). Though nocturnal mean esophageal pH was comparable between the dexlansoprazole and omeprazole groups, its duration was less with the former (181.5 [15.2-334.2] vs. 283 [158-366] min, p = 0.03). NAB was as frequent in the H. pylori-infected than the non-infected group (11/19 [57.9%] vs. 45/61 [73.8%]; p = 0.1). The nocturnal gastric and esophageal pH in the H. pylori-infected group was higher than in the non-infected group (4.6 ± 1.7 vs. 4 ± 1.6, p = 0.157; 6.1 ± 0.6 vs. 5.8 ± 0.6, p = 0.128). Dexlansoprazole tended to increase 24-h and nocturnal mean gastric pH among H. pylori-infected more than omeprazole (5.9 ± 1.1 vs. 4.2 ± 1.7, p = 0.023; 5.7 ± 1.2 vs. 3.8 ± 1.5, p = 0.006).. Dexlansoprazole is more effective than omeprazole in suppressing gastric acid secretion, resulting in lesser EA and NAB, particularly in the presence of H. pylori.

Topics: Dexlansoprazole; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Urease

Approximately, 20% of patients with heartburn and normal endoscopic findings do not symptomatically improve on proton pump inhibitor (PPI) therapy making diagnosis and treatment uncertain. A biomarker distinguishing PPI-responsive from PPI-refractory heartburn is desirable.. We performed a pilot study assessing whether carboxy(C)-terminal fragments (CTFs) of e-cadherin in esophageal biopsies or amino(N)-terminal fragments (NTFs) of e-cadherin in serum could serve this purpose.. Twenty-nine patients with endoscopy-negative heartburn had esophageal biopsies for CTFs on Western blot and blood for serum NTFs on ELISA. All patients received dexlansoprazole 30 mg daily for 4 weeks, and heartburn was assessed by daily diary entry. Post-treatment blood samples were obtained for serum NTFs. A control group without GERD symptoms (n = 6) had biopsies for CTFs and a second control group (n = 20) blood serum for serum NTFs.. Twenty-seven of 29 patients (93.1%) with endoscopy-negative heartburn, but 0 of 6 controls, were positive for CTFs. All patients and controls had measureable serum NTFs, but mean NTFs were significantly higher in those with PPI-responsive heartburn compared to those with PPI-refractory heartburn and controls. Following treatment, 24 of 29 (82.8) patients had relief of heartburn, which associated with a decline in mean NTFs compared to controls. NTFs in PPI-refractory patients (n = 5) were similar to controls before and after PPI therapy.. When heartburn responds to PPI, elevated serum NTFs decline to normal. These data suggest that cleaved products of e-cadherin may serve as biomarkers of NERD. Further data are needed to assess and confirm this concept.

Topics: Adult; Antigens, CD; Biomarkers; Cadherins; Case-Control Studies; Dexlansoprazole; Esophagus; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Pilot Projects; Proton Pump Inhibitors

Higher body mass index (BMI) is a recognised risk factor for gastro-oesophageal reflux disease (GERD). Data regarding the impact of BMI on proton pump inhibitor (PPI) therapy are conflicting.. To assess the impact of BMI on baseline heartburn symptom severity and frequency and response to PPI therapy in patients with non-erosive GERD (NERD) or erosive oesophagitis (EO).. In post hoc analyses of phase 3 trial data, 621 NERD and 2692 EO patients were stratified by BMI (<25, 25 to <30 and ≥30 kg/m(2) ). NERD patients received either dexlansoprazole MR 30 mg or placebo daily for 4 weeks. EO patients received either dexlansoprazole MR 60 mg or lansoprazole 30 mg for 8 weeks. Symptom frequency and severity were assessed at baseline and subsequently by daily diary.. In both the NERD and EO cohorts, baseline heartburn severity increased with increasing BMI. The impact of PPI therapy on the reduction in heartburn symptom frequency and severity in both NERD and EO patients was similar across BMI categories. EO healing rates in patients treated with dexlansoprazole but not lansoprazole were higher in obese patients compared with those with a BMI <30 kg/m(2) . Differences between the PPIs were small.. The PPIs evaluated in this study reduced the frequency and severity of 24-h heartburn regardless of baseline BMI. In addition, because patients with higher BMI have more severe symptoms at baseline, they may experience greater therapeutic gain with dexlansoprazole (NERD and erosive oesophagitis) and possibly lansoprazole (erosive oesophagitis) treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Clinical Trials as Topic; Dexlansoprazole; Dose-Response Relationship, Drug; Esophagitis; Female; Gastroesophageal Reflux; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Risk Factors; Severity of Illness Index; Treatment Outcome; Young Adult

Dexlansoprazole is a new proton pump inhibitor (PPI) with a dual delayed-release system. Both dexlansoprazole and esomeprazole are an enantiomer of lansoprazole and omeprazole respectively. However, there is no head-to-head trial data or indirect comparison analyses between dexlansoprazole and esomeprazole.. To compare the efficacy of dexlansoprazole with esomeprazole in healing erosive oesophagitis (EO), the maintenance of healed EO and the treatment of non-erosive reflux disease (NERD).. Randomised Controlled Trials (RCTs) comparing dexlansoprazole or esomeprazole with either placebo or another PPI were systematically reviewed. Random-effect meta-analyses and adjusted indirect comparisons were conducted to compare the treatment effect of dexlansoprazole and esomeprazole using a common comparator. The relative risk (RR) and 95% confidence interval (CI) were calculated.. The indirect comparisons revealed significant differences in symptom control of heartburn in patients with NERD at 4 weeks. Dexlansoprazole 30 mg was more effective than esomeprazole 20 mg or 40 mg (RR: 2.01, 95% CI: 1.15-3.51; RR: 2.17, 95% CI: 1.39-3.38). However, there were no statistically significant differences between the two drugs in EO healing and maintenance of healed EO. Comparison of symptom control in healed EO was not able to be made due to different definitions used in the RCTs.. Adjusted indirect comparisons based on currently available RCT data suggested significantly better treatment effect in symptom control of heartburn in patients with NERD for dexlansoprazole against esomeprazole. No statistically significant differences were found in other EO outcomes. However, these study findings need to be interpreted with caution due to small number of studies and other limitations.

Topics: Dexlansoprazole; Dose-Response Relationship, Drug; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome

Occasional acid reflux occurs frequently in the general population but gastroesophageal reflux disease (GERD), a chronic disease that affects millions of adults and children, is diagnosed if persistent reflux occurs more than twice a week. The development of proton pump inhibitors (PPIs) dramatically improved the treatment of GERD; however, the treatment of patients with refractory GERD remains a challenge. Dexlansoprazole (TAK-390MR, Kapidex), a pure enantiomer of lansoprazole, is a PPI that, with a novel dual delayed release formulation, provides prolonged inhibition of gastric acid secretion resulting in marked improvements in symptoms of GERD with high maintenance rates and good tolerability. Dexlansoprazole recently received Food and Drug Administration approval for the once-daily oral treatment of heartburn associated with symptomatic nonerosive GERD, the healing of erosive esophagitis (EE) and the maintenance of healed EE.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Child; Clinical Trials as Topic; Dexlansoprazole; Esophagitis; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors

Dexlansoprazole MR is a novel Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to prolong the plasma concentration-time profile of dexlansoprazole and extend duration of acid suppression with once-daily (QD) dosing.. To assess the pharmacokinetics and pharmacodynamics of dexlansoprazole at different doses of dexlansoprazole MR and delineate the exposure-response relationship following oral administration of dexlansoprazole MR.. Dexlansoprazole MR was evaluated in two prospective randomized studies in healthy subjects. In study 1 (n = 40), subjects received dexlansoprazole MR 60, 90, and 120 mg and lansoprazole 30 mg QD. In study 2 (n = 45), subjects received dexlansoprazole MR 30 and 60 mg and lansoprazole 15 mg QD. Data from these trials were pooled and analyzed to describe the relationship between intragastric pH and dexlansoprazole systemic exposure.. Data from 83 subjects were analyzed. The dexlansoprazole plasma concentration-time profile following administration of dexlansoprazole MR was characterized by two distinct peaks and a prolonged drug exposure during the 24-h dosing interval. Approximate dose proportionality was observed for mean peak plasma concentration and area under the plasma-concentration time curve after administration of dexlansoprazole MR. In each study, doses of dexlansoprazole MR generally produced greater gastric acid suppression than lansoprazole. Based on the exposure-response analysis using combined data from these two trials, the predicted mean 24-h intragastric pH values were 4.06 and 4.35 for the dexlansoprazole MR 30- and 90-mg doses, respectively. The percent of time pH > 4 over 24 h values were 59.2% and 66.7% for dexlansoprazole MR 30 and 90 mg, respectively. No appreciable additional gain in the pharmacodynamic response was predicted for dexlansoprazole MR 120 mg. Despite combining data from two studies to evaluate a broader dose range, this analysis provided a reasonable estimate of the pharmacodynamic parameters and a good characterization of the dexlansoprazole MR exposure-response relationship.. Dexlansoprazole MR, a proton pump inhibitor that uses Dual Delayed Release technology, produced a pharmacokinetic profile with a plasma concentration-time curve characterized by two distinct peaks and an extended duration of pharmacologically active dexlansoprazole concentration in plasma. Exposure-response analysis indicated a progressive increase in the pharmacodynamic response as dexlansoprazole MR doses increased from 30 to 90 mg.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Area Under Curve; Dexlansoprazole; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Clinical Trials as Topic; Delayed-Action Preparations; Dexlansoprazole; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Lansoprazole; Proton Pump Inhibitors; Treatment Outcome

Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole.. To assess safety of dexlansoprazole MR in phase 3 clinical trials.. Data from 4270 patients receiving dexlansoprazole MR 30 mg (n = 455), 60 mg (n = 2311) or 90 mg (n = 1864); lansoprazole 30 mg (n = 1363); or placebo (n = 896) in six randomized controlled trials and a 12-month safety study were pooled. Safety was assessed via adverse events, vital signs, electrocardiograms, clinical laboratory results and gastric biopsies. Adverse events were summarized per 100 patient-months of exposure to account for imbalances in study drug exposure.. The number of patients with > or =1 treatment-emergent adverse event per 100 patient-months was higher in placebo (24.49) and lansoprazole (21.06) groups than in any dexlansoprazole MR (15.64-18.75) group. Fewer patients receiving dexlansoprazole MR discontinued therapy because of an adverse event (P < or = 0.05 vs. placebo). Seven patients died of events considered unrelated to study drug. Mean serum gastrin rose in all groups except placebo; increases were not dose-related. No clinically concerning trends were seen in gastric biopsy results. Endocrine cell hyperplasia, dysplasia and neoplasia were not observed.. Dexlansoprazole MR 30-90 mg has a safety profile comparable to that of lansoprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Clinical Trials as Topic; Delayed-Action Preparations; Dexlansoprazole; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome