dexlansoprazole and Esophagitis

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

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

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

Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole.. To assess the efficacy and safety of dexlansoprazole MR in healing erosive oesophagitis (EO).. Patients in two identical double-blind, randomized controlled trials (n = 4092) received dexlansoprazole MR 60 or 90 mg or lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing procedure--first for non-inferiority, then superiority, vs. lansoprazole. Secondary endpoints included week 4 healing and week 8 healing in patients with moderate-to-severe disease (Los Angeles Classification grades C and D). Life-table and crude rate analyses were performed. Symptoms and tolerability were assessed.. Dexlansoprazole MR achieved non-inferiority to lansoprazole, allowing testing for superiority. Using life-table analysis, dexlansoprazole MR healed 92-95% of patients in individual studies vs. 86-92% for lansoprazole; the differences were not statistically significant (P > 0.025). Using crude rate analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies and 60 mg was superior in one study. Week 4 healing was > 64% with all treatments in both studies. In an integrated analysis of 8-week healing in patients with moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All treatments effectively relieved symptoms and were well tolerated.. Dexlansoprazole MR is highly effective in healing EO and offers benefits over lansoprazole, particularly in moderate-to-severe disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Aged, 80 and over; Delayed-Action Preparations; Dexlansoprazole; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis; Female; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome; Young Adult

Dexlansoprazole MR heals all grades of erosive oesophagitis (EO).. To assess efficacy and safety of dexlansoprazole MR in maintaining healed EO and heartburn relief.. In this randomized, double-blind trial, 445 patients with healed EO received dexlansoprazole MR 30 mg or 60 mg or placebo once daily for 6 months. This trial assessed maintenance of endoscopic healing (primary endpoint) and continued symptom relief based on daily diaries (secondary endpoints).. Dexlansoprazole MR 30 mg and 60 mg were superior to placebo for maintaining healed EO (P < 0.0025; Hochberg's). By life-table analysis, maintenance rates were 75%, 83% and 27% for dexlansoprazole MR 30 mg, 60 mg and placebo respectively. Crude maintenance rates were 66% for both dexlansoprazole MR doses and 14% for placebo. Dexlansoprazole MR controlled heartburn (medians of 91-96% for 24-h heartburn-free days, 96-99% for heartburn-free nights). The only more common adverse event occurring at a significantly higher rate in dexlansoprazole MR groups than placebo when analysed per patient-months of exposure was upper respiratory tract infection.. Dexlansoprazole MR effectively maintained EO healing and symptom relief; most patients were heartburn-free for >90% of days. Both doses were well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Delayed-Action Preparations; Dexlansoprazole; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis; Female; Gastric Mucosa; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Patient Satisfaction; Proton Pump Inhibitors; Quality of Life; Secondary Prevention; Treatment Outcome

Dexlansoprazole MR, a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, effectively heals erosive oesophagitis.. To assess dexlansoprazole MR in maintaining healed erosive oesophagitis.. Patients (n = 451) with erosive oesophagitis healed in either of two dexlansoprazole MR healing trials randomly received dexlansoprazole MR 60 or 90 mg or placebo once daily in this double-blind trial. The percentage of patients who maintained healing at month 6 was analysed using life table and crude rate methods. Secondary endpoints were percentages of nights and of 24-h days without heartburn based on daily diaries.. Dexlansoprazole MR 60 and 90 mg were superior to placebo for maintaining healing (P < 0.0025). Maintenance rates were 87% and 82% for the 60 and 90 mg doses, respectively, vs. 26% for placebo (life table), and 66% and 65% vs. 14%, respectively (crude rate). Both doses were superior to placebo for the percentage of 24-h heartburn-free days (60 mg, 96%; 90 mg, 94%; placebo, 19%) and nights (98%, 97%, and 50%, respectively). Diarrhoea, flatulence, gastritis (symptoms) and abdominal pain occurred more frequently with dexlansoprazole MR than placebo, but were not dose-related.. Dexlansoprazole MR effectively maintained healed erosive oesophagitis and symptom relief compared with placebo, and was well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Dexlansoprazole; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis; Female; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Treatment Outcome

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

Withdrawal of proton pump inhibitors (PPIs) may induce symptoms in healthy volunteers, suggesting that discontinuing PPI therapy induces acid-peptic disease. Similar assessments in patients with documented acid-related disorders are lacking.. We performed a retrospective analysis of data from 287 Helicobacter pylori-negative erosive esophagitis (EE) patients healed after 4 or 8 weeks of therapy with dexlansoprazole modified release (MR) or lansoprazole, and then randomized to placebo in 6-month maintenance trials. We compared serum gastrin levels and 24-h heartburn severity before enrollment in the healing trials (baseline) and after receiving placebo in the 6-month maintenance trials.. Mean gastrin values at maintenance months 1 and 3 were essentially unchanged (median changes, 1.0 and -1.0 pg/ml), showing that gastrin normalized within 1 month of discontinuing PPIs and remained flat. Mean heartburn severity at maintenance month 1 was <1 on a 5-point scale (1=mild) and significantly lower than at baseline (median decrease, 0.41 points; P≤0.001). Heartburn severity in patients healed at week 4 or 8 with either PPI was generally similar, suggesting that neither longer exposure nor more potent therapy was associated with rebound. In those with month 2 data, mean heartburn severity at months 1 and 2 was significantly lower than baseline (median decrease, 0.54 and 0.58 points; both P<0.001), indicating an ongoing symptom response for 2 months after PPI withdrawal.. In H. pylori-negative EE patients, there was no indication of recurring heartburn symptom worsening beyond baseline levels within 2 months of discontinuing 4-8 weeks of PPI therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Dexlansoprazole; Esophagitis; Female; Gastric Acid; Gastrins; Heartburn; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index; Withholding Treatment

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