Naproxen 500mg / Esomeprazole 20mg modified-release tablets

PURPOSE: Most of the previous meta-analyses examining the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on preventing heterotopic ossification (HO) following total hip arthroplasty (THA) have separately analyzed Brooker's classification I, II, III, and IV which may misrepresent their ordinal nature. We therefore applied a Bayesian network meta-regression that incorporates the ordinal nature of Brooker's classification to more robustly assess NSAID efficacy and determine the optimal regimen. METHODS: We searched the Cochrane Library, Embase, and PubMed for randomized controlled trials (RCTs). Cumulative regressions were conducted for ordinal variants to generate Napierian Logarithm odds ratios (lnOR) and the standard error of lnOR (selnOR) for each study. Subsequently these data were used to conduct Bayesian network meta-analysis and further network meta-regression to generate pairwise ORs, showing pairwise effect sizes (ESs). RESULTS: 17 studies (5436 patients,14 regimens) were eligible. In the raw data analysis, celecoxib 400 mg/d, etoricoxib 90 mg/d, ibuprofen 1200 mg/d, indomethacin 75 mg/d, indomethacin 100 mg/d, indomethacin 150 mg/d, meloxicam 7.5 mg/d, meloxicam 15 mg/d, and naproxen 750 mg/d were conspicuously effective (OR: 0.048 ~ 0.351) compared with placebo. The ESs were comparable among these regimens except for ibuprofen 1200 mg/d, which was inferior to indomethacin 100 mg/d (OR = 0.382, 95%CI: 0.171 to 0.887) and indomethacin 150 mg/d (OR = 0.136, 95%CI: 0.020 to 0.970). In the network meta-regression analysis, after adjusting for follow-up time, the significance of diclofenac 150 mg/d (OR = 0.102, 95%CI: 0.013 to 0.835) emerged compared with placebo. The results of effective regimens aforementioned resembled the initial findings (OR: 0.039 ~ 0.249). All the effective agents, including diclofenac 150 mg/d, were comparable in ESs. CONCLUSIONS: Considering the efficacy of preventing HO following THA observed in our research, together with analgesic effect and gastrointestinal tract safety from previous literature, etoricoxib 90 mg/d is recommended as the optimal choice for patient undergoing THA. More head-to-head and long-term studies are needed.

Abstract licence: CC BY-NC-ND

Background/Objectives: Celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), is widely prescribed for pain management due to its efficacy and improved gastrointestinal safety profile compared to traditional NSAIDs. Understanding prescription trends and their comparison to other NSAIDs provides valuable insight into prescribing behaviors in clinical settings. Methods: This retrospective study analyzed celecoxib prescriptions written by three pain management physicians in a single institution over a 16-month period from 1 January 2023 to 30 April 2024. Prescription data were collected and grouped into four 4-month intervals to assess temporal trends. Additionally, we compared celecoxib prescriptions to other commonly prescribed NSAIDs, including ibuprofen, meloxicam, naproxen, and diclofenac. Results: A total of 143 celecoxib prescriptions were identified during the study period, with a steady increase observed across consecutive intervals: 8 prescriptions from January–April 2023, 22 from May–August 2023, 46 from September–December 2023, and 67 from January–April 2024. In comparison, a total of 165 prescriptions were written for other NSAIDs over the same period, with 26 prescriptions from January–April 2023, 41 from May–August 2023, 45 from September–December 2023, and 53 from January–April 2024. While prescriptions for both celecoxib and other NSAIDs increased over time, the rate of celecoxib prescriptions showed a steeper rise. Conclusions: The findings demonstrate a notable increase in celecoxib prescriptions in this pain management clinic, outpacing the growth of other NSAIDs. This trend may reflect increasing provider preference for COX-2 selective inhibitors due to their favorable safety profile and efficacy. Further research is warranted to explore the underlying factors driving these prescribing patterns.

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BACKGROUND AND OBJECTIVES: There are currently no treatments that can halt or slow the progression of Parkinson disease (PD). The aim of this study was to identify new drug repurposing candidates for PD among existing prescription drugs that could be used to modify the disease course. METHODS: This nationwide observational cohort study (2004-2020) used Norwegian health registries and was conducted as a high-throughput drug screen using an emulated target trial design. All individuals who met our prescription-based classification criteria for PD, were older than 25 years at the time of diagnosis, and were not prescribed the target drug in the past 2 years were included. We emulated a target trial for any drug filled by a minimum of 100 individuals at any pharmacy in Norway, which amounted to a total of 219 drugs. Mortality was used as an outcome to indicate disease progression. We estimated the effect of drug initiation, an observational analog of the intention-to-treat effect, on the 8-year risk of death, comparing initiators of the target drug with initiators of drugs within the same Anatomical Therapeutic Chemical classification system level 1 group. Inverse probability of treatment weighting was used to adjust for potential confounders. RESULTS: The study included 14,289 individuals with PD (mean age 72 at diagnosis, 59% male) and identified 23 drugs associated with reduced mortality risk at 8 years. These drugs included ranitidine (histamine-2 blocker); pantoprazole and esomeprazole (proton pump inhibitors); losartan (angiotensin receptor blocker); atorvastatin (for high cholesterol); tadalafil (for erectile dysfunction); levothyroxine sodium (thyroid hormone); phenoxymethylpenicillin, erythromycin, and azithromycin (antibiotics); 4 nonsteroidal anti-inflammatory drugs; combined codeine/paracetamol and tramadol (opioid analgesics); zopiclone and melatonin (sleep aids); mianserin (antidepressant); mometasone (nasal corticosteroid); 2 opium-derived cough medicines; and dexamethasone (ophthalmologic corticosteroid). DISCUSSION: Our study identified several drugs with potential disease-modifying properties that could be candidates for future clinical trials. It highlights the potential of repurposing existing medications to advance drug development. While these findings are exploratory and, therefore, insufficient to justify immediate clinical application, they warrant further investigation and potential inclusion in clinical trials.

Abstract licence: CC BY

PURPOSE: Clopidogrel, an antiplatelet agent used to prevent ischemic events, may interact with proton pump inhibitors (PPIs), especially omeprazole and esomeprazole, and reduce its effectiveness. The evidence surrounding this interaction remains controversial. This study investigates whether co-prescribing clopidogrel with PPIs is associated with a higher incidence of major adverse cardiovascular events (MACEs) compared to clopidogrel monotherapy. METHODS: We conducted a retrospective cohort study analyzing data from the Real-world Evidence Research Network in Saudi Arabia from 2016 to 2023. Patients were followed from their initial clopidogrel prescription until the occurrence of MACEs or the end of follow-up. We employed stabilized inverse probability of treatment weighting (SIPTW) to adjust for potential confounders and the Cox proportional hazards model to assess risks. RESULTS: A total of 29 572 patients were included, with 21 480 in the clopidogrel + PPI group and 8092 in the clopidogrel-only group. Baseline characteristics were balanced post SIPTW, with similar mean ages (clopidogrel + PPI: 65.9 years; clopidogrel only: 66.1 years) and 64% male representation. The incidence rate of MACE was 3.22 versus 2.92 per 10 000 person-days in the clopidogrel + PPI and clopidogrel-only groups, respectively. The weighted hazard ratio for MACE was 1.20 (95% CI, 1.01-1.43). CONCLUSIONS: In this large real-world cohort study, we observed a modest but statistically significant increase in the risk of MACEs among patients who received concomitant clopidogrel and proton pump inhibitor therapy. Given the widespread use of these medications, these findings emphasize the need for individualized risk assessments when co-prescribing PPIs and clopidogrel.

Abstract licence: CC BY-NC

Background: Proton pump inhibitors (PPIs) and potassium competitive acid blockers (P-CABs) are widely used to treat acid-related diseases (ARDs). Precisely quantifying their plasma levels is crucial for clinical pharmacokinetic assessments and therapeutic drug monitoring. Aim: This study aimed to establish a generic and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for the determination of five PPIs (esomeprazole, rabeprazole, ilaprazole, lansoprazole, and pantoprazole) and the P-CAB (vonoprazan) in human plasma. Methods: The six analytes were extracted from human plasma via protein precipitation and a single dilution step. Detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization. Chromatographic separation was achieved on the ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) using gradient elution. The mobile elution was composed of 0.2% formic acid in acetonitrile (mobile phase A), 0.1% ammonium hydroxide and 10 mmol/L ammonium formate in deionized water (mobile phase B). The flow rate was 0.4 mL/min, the run time was 4.5 minutes, and the injection volume was 20 µL. Results & Conclusions: The method exhibited excellent linearity across the ranges of 0.2-200 ng/mL for PPIs and 0.5-500 ng/mL for the P-CAB. Both intra- and inter-day precision and accuracy were within the acceptance criteria, with precision ranging from 1.1% to 14.6% and accuracy ranging from 0.0% to 14.7%. Extraction recoveries were consistent, ranging from 88.1% to 96.7%, with no significant matrix effects observed. The stability of the six analytes under diverse storage and processing conditions was also confirmed, with both precision and accuracy falling within the acceptable range of 15%. The UPLC-MS/MS assay provided an efficient and reliable approach for the simultaneous determination of six acid-suppressing medications in a single analytical run. It has been successfully applied to the pharmacokinetic studies of PPIs and P-CABs, offering a valuable tool for clinical research and therapeutic drug monitoring.

Abstract licence: CC BY-NC

This study presents an innovative, structurally engineered, pulsatile oral drug delivery platform that enables programmable, sequential drug release by integrating a structurally engineered three-dimensional (3D)-printed capsular device with conventional immediate-release (IR) tablets. Unlike coating-based or multilayer systems, which suffer from complex manufacturing and inconsistent release profiles, the multi-compartment capsule provides precise and reproducible control over the release timing through simple structural modifications. Each compartment accommodated intact IR tablets, allowing immediate release from the open-window sections and delayed release from the barrier-enclosed compartments. The lag time (Tlag) before drug release can be predictably tuned by adjusting the barrier wall thickness. The system was optimized for esomeprazole and naproxen, for which gastroprotection requires temporally separated exposure. The in vitro dissolution displayed immediate release of esomeprazole and delayed release of naproxen with Tlag of 11.33 ± 1.37 h. Both immediate absorption of esomeprazole and delayed absorption of naproxen were observed following oral administration in beagle dogs. The time to maximum plasma concentration (Tmax) of esomeprazole was 0.67 ± 0.67 h, whereas the Tmax of naproxen was 9.83 ± 2.40 h with a Tlag of 4.75 ± 1.17 h. These findings demonstrate that this modular 3D-printed platform, combined with conventional tablets, provides controlled and sequential drug delivery, thereby supporting patient-tailored therapeutic regimens.

Abstract licence: CC BY-NC-ND