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Pharmacotherapy Feb 2024Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs).
METHODS
To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA).
RESULTS
Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB.
CONCLUSIONS
This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.
Topics: Humans; Adult; Pharmaceutical Preparations; Network Meta-Analysis; Proton Pump Inhibitors; Rabeprazole; Histamine H2 Antagonists; Benzene Derivatives; Imidazoles; Pyrroles; Sulfonamides
PubMed: 38049205
DOI: 10.1002/phar.2899 -
Cureus Oct 2023Current practice for patients with suspected or confirmed upper gastrointestinal bleeding (GIB) is to utilize a proton pump inhibitor (PPI) bolus followed by a...
Comparison Between Pantoprazole Intermittent Dosing and Continuous Infusion in Suspected Upper Gastrointestinal Bleeding Prior to Endoscopy: Impact of a Pharmacist-Driven Protocol to Reduce Utilization of Pantoprazole Continuous Infusion.
BACKGROUND
Current practice for patients with suspected or confirmed upper gastrointestinal bleeding (GIB) is to utilize a proton pump inhibitor (PPI) bolus followed by a continuous infusion for 72 hours. Literature has shown similar outcomes with intermittent bolus dosing compared to continuous infusion. Substitution would lead to reduced costs and utilization of resources.
METHODS
This was a retrospective case-control study conducted via chart review. Utilizing electronic healthcare record reports, patients in the control arm were screened for inclusion if they received a pantoprazole continuous infusion from December 1, 2020, to March 31, 2021. A total of 38 patients were included in the control arm. Patients in the experimental arm were screened for inclusion with pantoprazole intermittent therapy from January 1, 2022, to June 30, 2022. A total of 60 patients were included in the experimental arm. The primary outcome was a 30-day GIB recurrence. Secondary outcomes included 30-day hospital readmission, 30-day (), hospital length of stay (LOS), and number of pantoprazole vials utilized.
RESULTS
There was a 65% reduction in the 30-day GIB recurrence in the intermittent bolus arm compared to the continuous infusion arm. Thirty-day hospital readmission was 57% lower in the intermittent bolus arm compared to the continuous infusion arm. The LOS between the two arms was almost identical with the median being five days for the intermittent bolus arm and the median being four days for the continuous infusion arm. The 30-day infection rate had 5% of patients acquiring in the intermittent bolus arm and 2.5% in the continuous infusion arm. The intermittent bolus arm used 55% fewer pantoprazole vials than the continuous infusion arm.
CONCLUSION
In hospitalized patients, the utilization of pantoprazole intermittent bolus is not only comparably efficacious but potentially represents a safer and economically advantageous alternative compared to the current guideline recommendation of a 72-hour pantoprazole continuous infusion. Further studies could provide more robust data to support our findings and challenge the current recommendation for patients who meet the indication criteria.
PubMed: 38046478
DOI: 10.7759/cureus.48056 -
Critical Care and Resuscitation :... Jun 2022Medications prescribed for indications or at doses, frequencies or durations not approved by the Australian Therapeutic Goods Administration are considered "off- label"....
Medications prescribed for indications or at doses, frequencies or durations not approved by the Australian Therapeutic Goods Administration are considered "off- label". Critical illness makes seeking consent for off-label medication use impractical. We aimed to characterise the extent of off-label medication use in a tertiary medical- surgical intensive care unit (ICU) by auditing the electronic health records of all patients admitted over a one-month period. We found 25.4% of 2292 prescriptions made for 142 patients were off-label. Eighty-one (37.2%) of the total of 218 different prescribed medications were used at least once for an off-label indication. Medications commonly prescribed off-label included antacids (pantoprazole, esomeprazole), analgesics (fentanyl, morphine, ketamine, pregabalin), anticonvulsants (levetiracetam), antibiotics (cefazolin, erythromycin), antipsychotics (quetiapine, haloperidol), and cardiovascular agents (metoprolol, clonidine). Nearly all patients (88.0%) received at least one off-label medication during their ICU stay. Most off- label medications were used for conventional (albeit not licensed) reasons, but nine out of 81 (11.1%) were not; for example, acetazolamide for hypertension, aminophylline for oliguria, and dexmedetomidine for seizures. Recognising the challenges of formally registering an indication with the Therapeutic Goods Administration, but also the value of reducing the incidence of medications used for potentially incorrect purposes, we suggest guideline endorsement of what constitutes standard critical care practice as an alternative to regulatory control.
PubMed: 38045597
DOI: 10.51893/2022.2.OA8 -
Qatar Medical Journal 2023Methotrexate (MTX) is a folic acid antagonist used to treat different immunological or proliferative illnesses because of its anti-proliferative and anti-inflammatory...
INTRODUCTION
Methotrexate (MTX) is a folic acid antagonist used to treat different immunological or proliferative illnesses because of its anti-proliferative and anti-inflammatory effects. MTX Toxicity is considered a severe problem. Although acute toxicity related to high-dose administration (doses ≥500 mg/m) can be predicted based on the given dose, chronic toxicity still has no specific factors to predict it, so treatment depends on the history and symptoms of toxicity. MTX was initially used for oncology indications with high cyclic doses, then expanded to non-oncology indications with different low doses and frequencies. This significant change in doses resulted in dosing errors that contributed to MTX toxicity reports. Measures to prevent the toxicity of MTX should be implemented.
CASE
A 66-year-old female patient ingested 10 mg of MTX daily for one month instead of the once-toxicity symptoms. The serum level of MTX was requested, and treatment with folinic acid was initiated until the patient improved with the discontinuation of MTX.
DISCUSSION
There is limited literature about the lack the total cumulative dose, duration of intake, or serum level of MTX. All this information was provided in this case report, but drug-drug interactions were not reviewed, although aspirin and pantoprazole were identified as having interactions with methotrexate in this patient. Minimum total cumulative dose identification may help assess the toxicity risk in such patients.
CONCLUSION
Low-dose MTX chronic toxicity still needs further information to guide the patient's risk of toxicity and when to initiate treatment. Safety-practical measures should be implemented to prevent such administration errors.
PubMed: 38026729
DOI: 10.5339/qmj.2023.31 -
Caspian Journal of Internal Medicine 2023() infection is strongly related to peptic ulcer disease, chronic gastritis, and gastric malignancies. Therefore, eradication is necessary in these cases. This study...
BACKGROUND
() infection is strongly related to peptic ulcer disease, chronic gastritis, and gastric malignancies. Therefore, eradication is necessary in these cases. This study was aimed to compare the efficacy of 14-day reverse hybrid therapy with standard 14-day concomitant regimen for eradication in Iran.
METHODS
Of the 317 patients with dyspepsia and infection enrolled in the study, 153 and 164 patients were randomly assigned to reverse hybrid and concomitant groups, respectively. The reverse hybrid regimen containing pantoprazole, amoxicillin, clarithromycin, and metronidazole was taken every 12 hours in the first 7 days, however, Clarithromycin and Metronidazole were discontinued within the next 7 days. Patients in the concomitant group also received the same drugs for 14-day. Eradication confirmation tests were used 8 weeks after the end of treatments.
RESULTS
A crowd of 281 patients continued the trial until the end. eradication rates based on intention to treat analysis were 71.2% (109/153) and 83.5% (137/164) in reverse hybrid and concomitant groups, respectively ( = 0.007). By the per-protocol analysis, rates of eradication were 85.8% (109/127) and 89% (137/154), respectively ( = 0.428). Severe side effects were few in both groups. More side effects were observed in concomitant group ( < 0.001), however, the severity of side effects was not statistically different between the two regimens ( = 0.314). Reverse hybrid regimen was better tolerated (98% vs. 91.5%, = 0.009).
CONCLUSION
Both 14-day reverse hybrid and concomitant regimens have a fair response rate in Iran.
PubMed: 38024170
DOI: 10.22088/cjim.14.4.68 -
Caspian Journal of Internal Medicine 2023() has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma.
BACKGROUND
() has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma.
METHODS
This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate eradication, fecal antigen test was performed 8 weeks after treatment.
RESULTS
The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects.
CONCLUSION
Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.
PubMed: 38024162
DOI: 10.22088/cjim.14.4.676 -
Medicine Nov 2023Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile...
RATIONALE
Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile pustules with erythema. However, its pathogenesis is not fully understood. Hydroxychloroquine is widely used for the treatment of autoimmune diseases. Some patients presenting with AGEP have IL36RN and CARD14 gene mutations. Our report describes a patient with rheumatoid arthritis and AGEP associated with hydroxychloroquine and a newly discovered CARD14 gene mutation.
PATIENT CONCERNS
A 28-year-old woman with rheumatoid arthritis, treated with leflunomide therapy without marked relief of joint pain, developed multiple rashes with pruritis covering the body 5 days after switching to hydroxychloroquine treatment.
DIAGNOSES
Based on the patient's history, symptoms, and histopathological findings, AGEP was diagnosed.
INTERVENTIONS
Whole-exome sequencing and Sanger validation revealed no mutations in the IL36RN gene; however, a CARD14 gene mutation was present. The patient was treated using ketotifen fumarate tablets, dexamethasone sodium phosphate, calcium gluconate injection, methylprednisolone injection, vitamins C and B12, hydrocortisone butyrate cream, Reed acne cream, potassium chloride tablets, and pantoprazole enteric-coated capsules.
OUTCOMES
The rash improved after 15 days.
LESSONS SUBSECTIONS
There has been little basic research on AGEP-related genetics, and the CARD14 mutation may underlie several pustular rashes, including AGEP and generalized pustular psoriasis. Follow-up studies and further accumulation of patient data are required.
Topics: Female; Humans; Adult; Hydroxychloroquine; Acute Generalized Exanthematous Pustulosis; Skin; Arthritis, Rheumatoid; Exanthema; Mutation; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; Interleukins
PubMed: 38013380
DOI: 10.1097/MD.0000000000036168 -
European Journal of Pharmaceutical... Mar 2024As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the...
As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the brain, which might be limited by the blood-brain barrier (BBB). It is highly possible to combine proton pump inhibitors (PPIs) with sertraline in clinical trials. Nevertheless, the role played by PPIs in regulating the transport of sertraline across the BBB remains unclear. Here, the impact of PPIs on the distribution of sertraline in the brain and the mechanisms involved were investigated. A mouse brain distribution study showed that Omeprazole (OME), Pantoprazole (PAN), Ilaprazole (ILA), and Esomeprazole (ESO) increased the area under the brain concentration-time curves (AUC) for sertraline by 2.02-, 3.18-, 3.04-, and 4.21-fold, respectively, after the 14-day administration of PPIs. Besides, PPIs significantly increased the permeability of sertraline in brain perfusion experiments, with PAN having the highest rank order, followed by ILA, OME, and ESO. In the tail suspension test (TST), co-administration PPI groups showed significantly shorter immobility time than the control group. In vitro, four PPIs inhibited sertraline efflux in breast cancer resistance protein (BCRP)-overexpressing MDCKII cells, and showed a mixed inhibition type. In this study, PPIs were further found to inhibit the mRNA and protein expression of brain BCRP. To sum up, the findings of this study revealed that PPIs could enhance the brain distribution and antidepressant effect of sertraline, which may be attributed to the inhibition of BCRP expression at the BBB by PPIs.
Topics: Animals; Mice; Proton Pump Inhibitors; ATP Binding Cassette Transporter, Subfamily G, Member 2; Sertraline; Blood-Brain Barrier; Neoplasm Proteins; Omeprazole; Esomeprazole; Antidepressive Agents; Pantoprazole; 2-Pyridinylmethylsulfinylbenzimidazoles
PubMed: 38006986
DOI: 10.1016/j.ejps.2023.106653 -
Journal of Clinical and Experimental... 2023Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are...
Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial.
BACKGROUND
Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients.
MATERIAL AND METHODS
We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40 mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL.
RESULTS
Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups ( < 0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan ( < 0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively ( < 0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding.
CONCLUSION
Short course of vonoprazan 20 mg/day is safe and superior to pantoprazole 40 mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.
PubMed: 37975046
DOI: 10.1016/j.jceh.2023.05.008 -
BMJ Open Nov 2023The e-aluating the nhibition of tress rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically...
INTRODUCTION
The e-aluating the nhibition of tress rosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.
METHODS AND ANALYSIS
REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.
ETHICS AND DISSEMINATION
All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to - Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.
TRIAL REGISTRATION NUMBER
NCT03374800.
Topics: Adolescent; Adult; Humans; Gastrointestinal Hemorrhage; Intensive Care Units; Pantoprazole; Pneumonia, Ventilator-Associated; Proton Pump Inhibitors; Respiration, Artificial; Randomized Controlled Trials as Topic
PubMed: 37968012
DOI: 10.1136/bmjopen-2023-075588