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Scientific Reports Feb 2021Proton pump inhibitors (PPIs) were widely used. Observational studies suggested increasing risk of kidney injury in patients with PPIs treatment. We gathered six PPI...
Proton pump inhibitors (PPIs) were widely used. Observational studies suggested increasing risk of kidney injury in patients with PPIs treatment. We gathered six PPI regimens and adverse reports of acute kidney injury (AKI) and chronic kidney disease (CKD) based on US FDA Adverse Event Reporting System (FAERS) database from 2004 to 2019. We employed reporting odds ratio (ROR) to detect signals. Finally, we identified 3187 PPIs-associated AKI cases and 3457 PPIs-associated CKD cases. We detected significant signals between PPIs and AKI as well as CKD. The signal strength was stronger for CKD (ROR = 8.80, 95% CI 8.49-9.13) than AKI (ROR = 3.95, 95% CI 3.81-4.10), while dexlansoprazole performed stronger association for CKD (ROR = 34.94, 95% CI 30.89-39.53) and AKI (ROR = 8.18, 95% CI 7.04-9.51) than the other five PPIs. The median time from PPIs use to event occurrence was 23 days for AKI and 177 days for CKD. PPIs-associated AKI resulted larger proportion of death, life-threatening, hospitalization and disability events than PPIs-associated CKD. By mining the FAERS big data, we provided more information between PPIs use and the AKI and CKD events. PPIs rational use should be repeatedly stressed.
Topics: Acute Kidney Injury; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Data Mining; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Proton Pump Inhibitors; Renal Insufficiency, Chronic; United States; United States Food and Drug Administration; Young Adult
PubMed: 33574396
DOI: 10.1038/s41598-021-83099-y -
Medicine Dec 2020Randomized trials and observation studies have revealed conflicting results regarding the interaction between clopidogrel and proton pump inhibitors (PPIs). The aim of... (Observational Study)
Observational Study
BACKGROUND
Randomized trials and observation studies have revealed conflicting results regarding the interaction between clopidogrel and proton pump inhibitors (PPIs). The aim of our study was to provide laboratory evidence regarding whether PPIs blunt the antiplatelet reactivity of clopidogrel.
METHODS
We included records of Asian patients who received clopidogrel treatment for cardiovascular or cerebrovascular events and the VerifyNow P2Y12 assay for platelet reactivity monitoring. The responsiveness of antiplatelet effect to clopidogrel was analyzed according to 3 criteria:Results: Patients treated without PPIs did not differ significantly from those concomitantly treated with PPIs in terms of levels of PI (25.7% ± 24.3% vs 23.0 ± 25.3%, P = .4315), PRU (187.3 ± 74.0 vs 197.4 ± 77.3, P = .3373), or responsiveness to antiplatelet (adjusted absolute risk, 3.5%; 95% confidence interval, - 10.7 to 17.7%; P = .6297). Patients treated with lansoprazole, esomeprazole, pantoprazole, and rabeprazole exhibited no significant differences in PRU or PI levels compared with those treated without PPIs. By contrast, patients treated with dexlansoprazole exhibited a significantly decreased level of PI (25.7% ± 24.3% vs 14.0% ± 21.6%, P = .0297) and responsiveness to clopidogrel under the criterion PI > 20% (adjusted absolute risk: 10.5%; 95% confidence interval: 2.6% to 43.6%; P = .0274).
CONCLUSION
No robust interaction between clopidogrel and PPIs was found, but caution should be exercised in the concomitant use of dexlansoprazole and clopidogrel in Asians.
Topics: Age Factors; Aged; Aged, 80 and over; Asian People; Clopidogrel; Comorbidity; Drug Interactions; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Receptors, Purinergic P2Y12; Sex Factors
PubMed: 33327360
DOI: 10.1097/MD.0000000000023695 -
Indian Journal of Pharmacology 2020Levofloxacin-based triple therapies are considered the standard regimen for eradication of Helicobacter pylori (H. pylori) due to decreased sensitivity to clarithromycin... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Levofloxacin-based triple therapies are considered the standard regimen for eradication of Helicobacter pylori (H. pylori) due to decreased sensitivity to clarithromycin and the optimal duration of therapy is still controversial. Besides, there is no complete evidence about dexlansoprazole efficacy in the eradication of H. pylori.
AIM
Our study aimed to determine the effectiveness of triple therapy based on levofloxacin-dexlansoprazole as a standard treatment for H. pylori infection and estimate the effect of H. pylori on lipid profile and hemoglobin (Hb).
MATERIALS AND METHODS
A pilot prospective randomized trial of a triple therapy based on levofloxacin-dexlansoprazole for H. pylori eradication was conducted at Damanhour Medical National Institute, Egypt; 66 participants with H. pylori infection received levofloxacin (500 mg/day) plus amoxicillin (1 g/12 h) plus dexlansoprazole (60 mg/day). All medications administrated orally for either 7 days or 10 days. Four weeks after treatment, the eradication was assessed by the stool antigen test.
RESULTS
The rate of eradication was 63.6% in levofloxacin, amoxicillin, and dexlansoprazole (LAD) 7-day group, and 90.9% in LAD 10-day group. In addition, laboratory test results showed a significant difference in Hb, low-density lipoprotein, high-density lipoprotein, triglyceride, and total cholesterol levels before and after treatment (P < 0.05).
CONCLUSION
LAD 10 days is the least duration that provides maximum efficacy for H. pylori in Egyptian participants. In addition, successful treatment of H. pylori infection may reduce the risk of anemia and dyslipidemia. Furthermore, all members of the patient's family should be screened for H. pylori to prevent recurrent infection.
Topics: Adolescent; Adult; Amoxicillin; Anti-Bacterial Agents; Dexlansoprazole; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Male; Middle Aged; Pilot Projects; Prospective Studies; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Young Adult
PubMed: 33283766
DOI: 10.4103/ijp.IJP_364_19 -
Clinical and Translational Science Jan 2021There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic...
There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on the indications for each actionable drug listed in Lexicomp. Among patients with an actionable gene-drug-diagnosis group, 49.3% had a diagnosis where the drug was a therapeutic option and PGx could be used to guide treatment selection. Among patients with an associated diagnosis, 30.9% had a prescription for the actionable drug allowing PGx guided dosing. Three genes (CYP2C19, CYP2D6, and CYP3A5) accounted for all the gene-drug-diagnosis groups with matching diagnoses and prescriptions. The most common gene-drug-diagnosis groups with matching diagnoses and prescriptions were CYP2C19-citalopram-escitalopram-depression 3.3% of patients tested; CYP2C19-dexlansoprazole-gastritis-esophagitis 3.1%; CYP2C19-omeprazole-gastritis-esophagitis 2.4%; CYP2D6-atomoxetine-attention deficit hyperactivity disorder 2.2%; and CYP2C19-citalopram-escitalopram-obsessive-compulsive disorder 1.5%. PGx could be used to guide selection of current treatment options or medication dosing in almost half (48.7%) of pediatric patients tested. Mood disorders and gastritis/esophagitis are promising targets for future study of PGx testing because of the high prevalence of these diagnoses and associated actionable gene-drug pairs in the pediatric population.
Topics: Academic Medical Centers; Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Clinical Decision-Making; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Depression; Dose-Response Relationship, Drug; Drug Prescriptions; Esophagitis; Feasibility Studies; Female; Gastritis; Hospitals, Pediatric; Humans; Male; Obsessive-Compulsive Disorder; Pharmacogenomic Testing; Pharmacogenomic Variants; Prescription Drugs; Retrospective Studies
PubMed: 33048453
DOI: 10.1111/cts.12895 -
Journal of Veterinary Internal Medicine Sep 2020Proton pump inhibitors (PPIs) are among the most commonly prescribed medications for esophagitis and upper gastrointestinal erosion and ulceration in cats. Newer PPIs...
BACKGROUND
Proton pump inhibitors (PPIs) are among the most commonly prescribed medications for esophagitis and upper gastrointestinal erosion and ulceration in cats. Newer PPIs such as lansoprazole and esomeprazole are believed to be effective in cats, but the effect of many of these PPIs on gastric pH in cats has not been explored.
HYPOTHESIS/OBJECTIVES
To evaluate the efficacy of PO esomeprazole, dexlansoprazole, and lansoprazole on intragastric pH in healthy cats. We hypothesized that esomeprazole and lansoprazole would provide superior acid suppression compared to dexlansoprazole and reach pH goals extrapolated from people for the treatment of esophagitis and duodenal ulceration.
ANIMALS
Twelve healthy research cats.
METHODS
Randomized, 3-way crossover study. Cats were given esomeprazole and lansoprazole at a dosage of 1 mg/kg PO q12h or dexlansoprazole at 6 mg/kg PO q12h. Intragastric pH was recorded at baseline and for 4 days of treatment. Mean pH and the mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were compared among and within treatment groups.
RESULTS
Cats treated with lansoprazole had a lower MPT ± SD of intragastric pH ≥3 (8.8 ± 6.8%) and mean ± SD pH (1.6 ± 0.5) than did cats treated with dexlansoprazole (41.2 ± 34.6% and 3.11 ± 1.6, respectively) or esomeprazole (54 ± 33.8% and 4.1 ± 3.9, respectively;P ≤ .04). Esomeprazole was the only treatment that achieved the goals defined for people for the treatment of duodenal ulceration by Day 4 of treatment (MPT ± SD of intragastric pH ≥4 of 77.1 ± 29.2%).
CONCLUSIONS AND CLINICAL IMPORTANCE
Orally administered esomeprazole might be a superior acid suppressant in cats compared to PO lansoprazole or dexlansoprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Ulcer Agents; Cats; Cross-Over Studies; Esomeprazole; Female; Hydrogen-Ion Concentration; Pilot Projects; Veterinary Drugs
PubMed: 32885499
DOI: 10.1111/jvim.15887 -
Estimating the Use of Potentially Inappropriate Medications Among Older Adults in the United States.Journal of the American Geriatrics... Dec 2020Inappropriate prescribing of medications is common in health care, and is an important safety concern, especially for older adults, who have a high burden of comorbidity...
OBJECTIVES
Inappropriate prescribing of medications is common in health care, and is an important safety concern, especially for older adults, who have a high burden of comorbidity and are at greater risk for medication-related adverse events. This study aims to estimate the extent and cost of potentially inappropriate prescribing of medications to older adults in the United States.
DESIGN
A cross-sectional study.
SETTING
Medicare Part D Prescription Drug Program data set (2014-2018).
PARTICIPANTS
Older adults who were enrolled in Medicare Part D Prescription Drug Program between 2014 and 2018.
MEASUREMENTS
Potentially inappropriate medications were identified using the 2019 American Geriatrics Society Beers Criteria®.
RESULTS
In 2018, 7.3 billion doses of potentially inappropriate medications were dispensed. The most common medications by number of doses dispensed were proton pump inhibitors, benzodiazepines, and tricyclic antidepressants, and the top five unique medications by reported spending were dexlansoprazole, esomeprazole, omeprazole, dronedarone, and conjugated estrogens. From 2014 to 2018, 43 billion doses of potentially inappropriate medications were dispensed, with a reported spending of $25.2 billion.
CONCLUSION
Potentially inappropriate medication use among older adults is both common and costly. Careful attention to potentially inappropriate medication use and deprescribing when clinically appropriate could reduce costs and potentially improve outcomes among older adults.
Topics: Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Benzodiazepines; Comorbidity; Cross-Sectional Studies; Female; Geriatrics; Humans; Inappropriate Prescribing; Male; Medicare Part D; Polypharmacy; Potentially Inappropriate Medication List; Proton Pump Inhibitors; United States
PubMed: 32841366
DOI: 10.1111/jgs.16779 -
Therapeutic Advances in Gastroenterology 2020Whether adjunctive -acetylcysteine (NAC) may improve the efficacy of triple therapy in the first-line treatment of infection remains unknown. Our aim was to compare the...
BACKGROUND
Whether adjunctive -acetylcysteine (NAC) may improve the efficacy of triple therapy in the first-line treatment of infection remains unknown. Our aim was to compare the efficacy of 14-day triple therapy with or without NAC for the first-line treatment of .
MATERIAL AND METHODS
Between 1 January 2014 and 30 June 2018, 680 patients with infection naïve to treatment were enrolled in this multicenter, open-label, randomized trial. Patients were randomly assigned to receive triple therapy with NAC [NAC-T14, dexlansoprazole 60 mg four times daily (q.d.); amoxicillin 1 g twice daily (b.i.d.), clarithromycin 500 mg b.i.d., NAC 600 mg b.i.d.] for 14 days, or triple therapy alone (T14, dexlansoprazole 60 mg q.d.; amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d.) for 14 days. Our primary outcome was the eradication rates by intention to treat (ITT). Antibiotic resistance and gene polymorphism were determined.
RESULTS
The ITT analysis demonstrated eradication rates in NAC-T14 and T14 were 81.7% [276/338, 95% confidence interval (CI): 77.5-85.8%] and 84.3% (285/338, 95% CI 80.4-88.2%), respectively. In 646 participants who adhered to their assigned therapy, the eradication rates were 85.7% and 88.0% with NAC-T14 and T14 therapies, respectively. There were no differences in compliance or adverse effects. The eradication rates in subjects with clarithromycin-resistant, amoxicillin-resistant, or either clarithromycin/amoxicillin resistant strains were 45.2%, 57.9%, and 52.2%, respectively, for NAC-T14, and were 66.7%, 76.9%, and 70.0%, respectively, for T14. The efficacy of NAC-T14 and T14 was not affected by polymorphism.
CONCLUSION
Add-on NAC to triple therapy was not superior to triple therapy alone for first-line eradication [ClinicalTrials.gov identifier: NCT02249546].
PubMed: 32821287
DOI: 10.1177/1756284820927306 -
Chemosphere Dec 2020Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our...
Urgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-approved drugs using a simple assay in the nematode C. elegans and found three compounds that caused morphological changes. While the anticoagulant ticlopidine and the antifungal sertaconazole caused both accumulations that resulted in distinct distortions of pharyngeal anatomy and lethality upon acute exposure, the proton-pump inhibitor dexlansoprazole caused molting defects and required exposure during larval development. Such easily detectable defects in a powerful genetic model system advocate the continued exploration of current medicines using a variety of model organisms to better understand drugs already prescribed to millions of patients.
Topics: Animals; Bioaccumulation; Caenorhabditis elegans; Dexlansoprazole; Drug Approval; Epigenesis, Genetic; Humans; Imidazoles; Larva; Molting; Mutation; Thiophenes; Ticlopidine; United States; United States Food and Drug Administration
PubMed: 32731027
DOI: 10.1016/j.chemosphere.2020.127756 -
Journal of Gastroenterology and... Dec 2020The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of the efficiency of two different proton pump inhibitor formula in treatment of patients with atypical gastroesophageal reflux disease: a prospective randomized study.
BACKGROUND AND AIM
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).
METHODS
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.
RESULTS
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.
CONCLUSIONS
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
PubMed: 32401385
DOI: 10.1111/jgh.15093 -
Critical Reviews in Analytical Chemistry 2021A detailed review to analyze the anti ulcer proton pump inhibitor (PPI) drugs, particularly for determination of their concentration percentage (assay) by analytical... (Review)
Review
A detailed review to analyze the anti ulcer proton pump inhibitor (PPI) drugs, particularly for determination of their concentration percentage (assay) by analytical methods developed on analytical instruments i.e., UV visible Spectrophotometer, High Performance Liquid Chromatography, Ultra Performance Liquid Chromatography, and Hyphenated techniques. The review includes literature survey of PPI drugs namely omeprazole (OPZ), lansoprazole (LPZ), pantoprazole (PPZ) rabeprazole (RPZ), dexlansoprazole (DLPZ), esomeprazole (EPZ), dexrabeprazole (DRPZ), ilaprazole (IPZ), and tenatoprazole (TPZ). The examined literature survey addressed chromatographic (HPLC and UPLC) and UV visible spectrophotometric methods with LC-MS/MS methods used in pure forms, pharmaceutical formulations, and human plasma and other biological fluids for their estimation. In case of validation parameters mostly Linearity, Recovery study, LOD and LOQ was considered and mentioned.
Topics: Chromatography, Liquid; Humans; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Tandem Mass Spectrometry
PubMed: 32312104
DOI: 10.1080/10408347.2020.1750339