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1
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Kawai T, Suzuki C, Honda Y, Fernandez JL. Long-term safety and effectiveness of vonoprazan for prevention of gastric and duodenal ulcer recurrence in patients on nonsteroidal anti-inflammatory drugs in Japan: a 12-month post-marketing surveillance study. Expert Opin Drug Saf 2022:1-7. [PMID: 36264125 DOI: 10.1080/14740338.2023.2136163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND This study assessed the safety and effectiveness of vonoprazan for prevention of duodenal and gastric ulcer recurrence in patients on long-term nonsteroidal anti-inflammatory drugs (NSAIDs) in routine clinical practice. RESEARCH DESIGN AND METHODS This 12-month, prospective, observational study (145 sites, Japan, September 2016-April 2020) analyzed patients with a history of gastric or duodenal ulcer who started once-daily vonoprazan and were receiving NSAIDs for pain or low-dose aspirin for thrombosis/embolism suppression. The primary outcome was the incidence of adverse drug reactions (ADRs). RESULTS Most patients (86.7% [1099/1268]) received vonoprazan for at least 6 months. Most patients (98.6% [1250/1268]) received the 10-mg dose of vonoprazan, 38.3% (486/1268) received cyclooxygenase-2 inhibitors, and 61.7% (782/1268) received other NSAIDs. The overall incidence of ADRs was 0.71% (9/1268). Most commonly reported ADRs were gastrointestinal (0.32%), nervous system (0.16%), and hepatobiliary system (0.16%) disorders. The overall incidence of gastric or duodenal ulcer recurrence was 1.04% (95% CI 0.56-1.78). CONCLUSIONS No new safety concerns were reported for vonoprazan for prevention of secondary ulcer or bleeding in patients receiving long-term NSAIDs. Vonoprazan was effective for preventing NSAID-related peptic ulcer recurrence in this real-world study. TRIAL REGISTRATION ClinicalTrials.gov: NCT03214198; Japan Pharmaceutical Information Center Clinical Trials Information: JapicCTI-163436.
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Affiliation(s)
- Takashi Kawai
- Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan
| | - Chihiro Suzuki
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Youichirou Honda
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
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2
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Mousavi T, Nikfar S, Abdollahi M. The pharmacotherapeutic management of duodenal and gastric ulcers. Expert Opin Pharmacother 2021; 23:63-89. [PMID: 34435515 DOI: 10.1080/14656566.2021.1959914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Although the incidence and prevalence of duodenal and gastric ulcers have been declining, it remains challenging for health care systems. Based on the underlying cause, history, and characteristics of ulcers, management is generally provided by administering proton pump inhibitors (PPIs) or antibiotics. AREAS COVERED This article is based on global guidelines and English language literature from the past decade obtained through searches using PubMed, Clinicaltrials.gov, the US FDA, and the Cochrane library. Using a stepwise approach, dose and duration of treatment, drug interactions, warnings and contraindications, adverse effects, and administration points were specified. New drug candidates that may get American and European approvals were also introduced. EXPERT OPINION Despite the wide use of PPIs, their development lags behind the clinical need. There is an absolute requirement to develop third-generation PPIs with higher potency and improved pharmacokinetic and safety profiles. Regarding the antibiotic resistance crisis, including those used against H. pylori, conducting more clinical trials and investigating regional antibiotic resistance are warranted. Potassium competitive acid blockers, ilaprazole, and an H. pylori vaccine all show promise for the future.
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Affiliation(s)
- Taraneh Mousavi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shekoufeh Nikfar
- Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.,Evidence-Based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, Pharmaceutical Sciences Research Center (PSRC), and the Pharmaceutical Management and Economics Research Center (PMERC), the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacoeconomics and Pharmaceutical Administration, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.,Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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3
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Karasawa Y, Kamae I, Nozawa K, Zeniya S, Murata T, Soen S, Sakamoto C. Cost-effectiveness analysis of branded and authorized generic celecoxib for patients with chronic pain in Japan. PLoS One 2021; 16:e0253547. [PMID: 34228745 PMCID: PMC8259992 DOI: 10.1371/journal.pone.0253547] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 06/07/2021] [Indexed: 12/03/2022] Open
Abstract
Objectives The aim of this study was to examine the cost-effectiveness of branded and authorized generic (AG) celecoxib for chronic pain patients with osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain (LBP), using real-world cost information for loxoprofen and pharmacotherapy for gastrointestinal bleeding. Methods This cost-effectiveness analysis was performed as a long-term simulation using the Markov model from the Japanese public healthcare payer’s perspective. The analysis was conducted using loxoprofen with real-world weighted price by branded/generic distribution (hereinafter, loxoprofen with weighted price) as a comparator. In the model, we simulated the prognosis of patients with chronic pain by OA, RA, and LBP treated with loxoprofen or celecoxib, over a lifetime period. Results A cost-increase of 129,688 JPY (1,245.00 USD) for branded celecoxib and a cost-reduction of 6,268 JPY (60.17 USD) for AG celecoxib were recognized per patient in lifetime horizon, compared to loxoprofen with weighted price. No case was recognized to reverse the results of cost-saving by AG celecoxib in one-way sensitivity analysis. The incremental cost-effectiveness ratio of branded celecoxib attained 5,403,667 JPY/QALY (51,875.20 USD/QALY), compared to loxoprofen with the weighted price. Conclusion The current cost-effectiveness analysis for AG celecoxib revealed its good value for costs, considering the patients’ future risk of gastrointestinal injury; also, the impact on costs due to AG celecoxib against loxoprofen will be small. It implies that the disadvantage of AG celecoxib being slightly more expensive than generic loxoprofen could be offset by the good cost-effectiveness during the prognosis.
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Affiliation(s)
- Yusuke Karasawa
- Medical Affairs, Viatris Pharmaceuticals Japan Inc., Tokyo, Japan
- * E-mail:
| | - Isao Kamae
- Department of Health Policy and Technology Assessment, Graduate School of Public Policy, The University of Tokyo, Tokyo, Japan
| | - Kazutaka Nozawa
- Medical Affairs, Viatris Pharmaceuticals Japan Inc., Tokyo, Japan
| | | | | | - Satoshi Soen
- Soen Orthopaedics, Osteoporosis and Rheumatology Clinic, Kobe, Japan
| | - Choitsu Sakamoto
- Department of Gastroenterology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
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4
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Kamada T, Satoh K, Itoh T, Ito M, Iwamoto J, Okimoto T, Kanno T, Sugimoto M, Chiba T, Nomura S, Mieda M, Hiraishi H, Yoshino J, Takagi A, Watanabe S, Koike K. Evidence-based clinical practice guidelines for peptic ulcer disease 2020. J Gastroenterol 2021; 56:303-322. [PMID: 33620586 PMCID: PMC8005399 DOI: 10.1007/s00535-021-01769-0] [Citation(s) in RCA: 129] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 02/03/2021] [Indexed: 02/05/2023]
Abstract
The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.
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Affiliation(s)
- Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1, Nakasange, Kita-ku, Okayama, 700-8505, Japan.
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
| | - Kiichi Satoh
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshiyuki Itoh
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masanori Ito
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Junichi Iwamoto
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tadayoshi Okimoto
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takeshi Kanno
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Mitsushige Sugimoto
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshimi Chiba
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Sachiyo Nomura
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Mitsuyo Mieda
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hideyuki Hiraishi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Junji Yoshino
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Atsushi Takagi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Sumio Watanabe
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Peptic Ulcer," the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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5
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Szeto CC, Sugano K, Wang JG, Fujimoto K, Whittle S, Modi GK, Chen CH, Park JB, Tam LS, Vareesangthip K, Tsoi KKF, Chan FKL. Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations. Gut 2020; 69:617-629. [PMID: 31937550 DOI: 10.1136/gutjnl-2019-319300] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 12/06/2019] [Accepted: 12/22/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, but they are associated with a number of serious adverse effects, including hypertension, cardiovascular disease, kidney injury and GI complications. OBJECTIVE To develop a set of multidisciplinary recommendations for the safe prescription of NSAIDs. METHODS Randomised control trials and observational studies published before January 2018 were reviewed, with 329 papers included for the synthesis of evidence-based recommendations. RESULTS Whenever possible, a NSAID should be avoided in patients with treatment-resistant hypertension, high risk of cardiovascular disease and severe chronic kidney disease (CKD). Before treatment with a NSAID is started, blood pressure should be measured, unrecognised CKD should be screened in high risk cases, and unexplained iron-deficiency anaemia should be investigated. For patients with high cardiovascular risk, and if NSAID treatment cannot be avoided, naproxen or celecoxib are preferred. For patients with a moderate risk of peptic ulcer disease, monotherapy with a non-selective NSAID plus a proton pump inhibitor (PPI), or a selective cyclo-oxygenase-2 (COX-2) inhibitor should be used; for those with a high risk of peptic ulcer disease, a selective COX-2 inhibitor plus PPI are needed. For patients with pre-existing hypertension receiving renin-angiotensin system blockers, empirical addition (or increase in the dose) of an antihypertensive agent of a different class should be considered. Blood pressure and renal function should be monitored in most cases. CONCLUSION NSAIDs are a valuable armamentarium in clinical medicine, but appropriate recognition of high-risk cases, selection of a specific agent, choice of ulcer prophylaxis and monitoring after therapy are necessary to minimise the risk of adverse events.
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Affiliation(s)
- Cheuk-Chun Szeto
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, New Territories, Hong Kong.,Asian Pacific Society of Nephrology (APSN), Hong Kong, Hong Kong
| | - Kentaro Sugano
- Jichi Medical University, Shimotsuke, Tochigi, Japan.,Asian Pacific Association of Gastroenterology (APAGE), Tochigi, Japan
| | - Ji-Guang Wang
- Shanghai Institute of Hypertension, Shanghai, Shanghai, China.,Asia Pacific Society of Hypertension (APSH), Shanghai, China
| | - Kazuma Fujimoto
- Saga University, Saga, Japan.,Asia-Pacific Society for Digestive Endoscopy (APSDE), Saga, Japan
| | - Samuel Whittle
- The University of Adelaide, Adelaide, South Australia, Australia.,Asia Pacific League of Associations for Rheumatology (APLAR), Adelaide, South Australia, Australia
| | - Gopesh K Modi
- Asian Pacific Society of Nephrology (APSN), Hong Kong, Hong Kong.,Samarpan Kidney Institute and Research Center, Bhopal, India
| | - Chen-Huen Chen
- National Yang-Ming University, Taipei, Taiwan.,Pulse of Asia (PoA), Taipei, Taiwan
| | - Jeong-Bae Park
- Pulse of Asia (PoA), Taipei, Taiwan.,JB Lab and Clinic and Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Lai-Shan Tam
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, New Territories, Hong Kong.,Asia Pacific League of Associations for Rheumatology (APLAR), Adelaide, South Australia, Australia
| | - Kriengsak Vareesangthip
- Asian Pacific Society of Nephrology (APSN), Hong Kong, Hong Kong.,Mahidol University, Nakorn Pathom, Thailand
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6
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Iwamoto J, Murakami M, Monma T, Ueda H, Tamamushi M, Konishi N, Yara SI, Hirayama T, Ikegami T, Honda A, Mizokami Y. Current states of prevention of drug-induced gastroduodenal ulcer in real clinical practice: a cross-sectional study. J Clin Biochem Nutr 2020; 66:158-162. [PMID: 32231413 DOI: 10.3164/jcbn.19-66] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 12/04/2019] [Indexed: 02/06/2023] Open
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA) are the most common causes of drug-induced gastroduodenal ulcer and We investigated preventive treatment with use of concomitant anti-ulcer drugs and the clinical features of gastroduodenal ulcer in cases treated with these drugs. Patients with gastroduodenal ulcer and patients with bleeding were classified into 3 groups: LDA, non-aspirin NSAIDs, and those taking neither aspirin nor NSAIDs. Chronological changes over the past 16 years (1st-5th period) were investigated. The status of prevention of ulcer and clinical features were examined. From January 2002 to December 2018, the ratio of all patients taking NSAIDs and LDA increased significantly until 3rd period (p<0.05), but then started to decrease in 4th period; and the percentage of all patients taking NSAIDs and LDA decreased significantly (p<0.05) until 5th period. Among the 292 patients with gastroduodenal ulcer and the 121 patients with a bleeding ulcer taking NSAIDs and LDA, 16 (5.5%) and 9 (7.4%), respectively, were receiving preventive treatment with concomitant anti-ulcer drugs. The percentages of patients taking LDA and other antiplatelet drugs in patients with bleeding gastroduodenal ulcer were significantly higher than those in patients with non-bleeding. In conclusion, although the percentages of patients with gastroduodenal ulcer taking NSAIDs or LDA have not recently increased in real-world practice, preventive treatment in these patients is still low. This low rate of prevention suggests the need to enlighten physicians about preventive treatment because drug withdrawal of LDA has a high risk of cardiovasculr and cerebrovascular events.
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Affiliation(s)
- Junichi Iwamoto
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Masashi Murakami
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Tadakuni Monma
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Hajime Ueda
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Makoto Tamamushi
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Naoki Konishi
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Sho-Ichiro Yara
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Takeshi Hirayama
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Tadashi Ikegami
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Akira Honda
- Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan.,Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Chuo 3-20-1, Ami, Inashiki, Ibaraki 300-0395, Japan
| | - Yuji Mizokami
- Department of Gastroenterology, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8577, Japan
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Wang CH, Li CH, Hsieh R, Fan CY, Hsu TC, Chang WC, Hsu WT, Lin YY, Lee CC. Proton pump inhibitors therapy and the risk of pneumonia: a systematic review and meta‐analysis of randomized controlled trials and observational studies. Expert Opin Drug Saf 2019; 18:163-172. [DOI: 10.1080/14740338.2019.1577820] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Chih-Hung Wang
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Han Li
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ronan Hsieh
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA
| | - Cheng-Yi Fan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tze-Chun Hsu
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Che Chang
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wan-Ting Hsu
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
| | - Yu-Ya Lin
- Department of Pharmacy, E-Da hospital, Kaohsiung, Taiwan
| | - Chien-Chang Lee
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
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8
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Sugisaki N, Iwakiri R, Tsuruoka N, Sakata Y, Shimoda R, Fujimoto S, Eguchi Y, Fujimoto K. A case-control study of the risk of upper gastrointestinal mucosal injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based on data from the Japanese national claims database of 13 million accumulated patients. J Gastroenterol 2018; 53:1253-1260. [PMID: 29948304 DOI: 10.1007/s00535-018-1483-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 06/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND We aimed to identify the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics on the upper gastrointestinal (GI) mucosa in a clinical setting as a case-control study using a large-scale medical database in Japan. METHODS We evaluated the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotics using the Japan Medical Data Center claims database with data for 13 million accumulated patients, from January 2009 to December 2014. Endoscopically evaluated upper GI mucosal injuries were peptic ulcers (n = 143,271), upper GI bleeding (n = 10,545), and gastroesophageal reflux disease (n = 154,755). For each patient, ten controls were matched by age, sex, and diagnosis month. RESULTS The odds ratio (OR) for peptic ulcers was 1.45, 1.31, 1.50, 1.53, and 1.62; for upper GI bleeding: 1.76, 1.62, 1.96, 1.82, and 2.38; and for gastroesophageal reflux disease: 1.54, 1.41, 1.89, 1.67, and 1.91 for NSAIDs, COX-2 selective inhibitors, low-dose aspirin, antiplatelet drugs, and anticoagulants, respectively (all statistically significant: P < 0.001). Polypharmacy with NSAIDs and antithrombotic drugs increased the risk of upper GI injuries compared with single-drug therapy. The injury risk was also increased by lifestyle-related diseases, including diabetes mellitus and hyperlipidemia. CONCLUSIONS This case-control study using the large organized Japanese claims database provided the risk of upper GI mucosal injuries in patients receiving NSAIDs and antithrombotic drugs.
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Affiliation(s)
- Nobuyuki Sugisaki
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
| | - Ryuichi Iwakiri
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Nanae Tsuruoka
- Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Yasuhisa Sakata
- Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Ryo Shimoda
- Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Shun Fujimoto
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.,Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Yuichiro Eguchi
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.,Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
| | - Kazuma Fujimoto
- Graduate School of Medical Science, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.,Department of Internal Medicine, Saga University, Saga, 849-8501, Japan
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9
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Liapikou A, Cilloniz C, Torres A. Drugs that increase the risk of community-acquired pneumonia: a narrative review. Expert Opin Drug Saf 2018; 17:991-1003. [PMID: 30196729 DOI: 10.1080/14740338.2018.1519545] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Community-acquired pneumonia (CAP), a major cause of morbidity and mortality, is the leading infectious cause of death in the developed world. Population-based studies and systematic reviews have identified a large number of risk factors for the development of pneumonia in adults. In addition to age, lifestyle habits, and comorbidities, some forms of pharmacotherapy may also increase the risk for CAP. AREAS COVERED MEDLINE, CENTRAL, and Web of Science were used in 2017 to search for case-control, cohort studies, as well as randomized controlled trials and meta-analysis that involved outpatient proton pump inhibitors (PPIs), inhaled corticosteroids (ICSs), antipsychotics, oral antidiabetics, and CAP diagnosis in patients aged >18 years. EXPERT OPINION Our review confirmed that the use of ICSs, PPIs or antipsychotic drugs was independently associated with an increased risk for CAP. We also identified a positive association between specific oral antidiabetics and the development of pneumonia.
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Affiliation(s)
- Adamantia Liapikou
- a 6th Respiratory Department , Sotiria Chest Diseases Hospital , Athens , Greece
| | - Catia Cilloniz
- b Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , University of Barcelona (UB) - SGR 911 - Ciber de Enfermedades Respiratorias (Ciberes) , Barcelona , Spain
| | - Antoni Torres
- b Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , University of Barcelona (UB) - SGR 911 - Ciber de Enfermedades Respiratorias (Ciberes) , Barcelona , Spain
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Oshima T, Miwa H. Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases. J Neurogastroenterol Motil 2018; 24:334-344. [PMID: 29739175 PMCID: PMC6034668 DOI: 10.5056/jnm18029] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/03/2018] [Accepted: 04/17/2018] [Indexed: 12/13/2022] Open
Abstract
Conventional proton pump inhibitors (PPIs) are used as a first-line therapy to treat acid-related diseases worldwide. However, they have a number of limitations including slow onset of action, influence by cytochrome P450 polymorphisms, unsatisfactory effects at night, and instability in acidic conditions. Alternative formulations of conventional PPIs have been developed to overcome these problems; however, these drugs have only introduced small advantages for controlling acid secretion compared to conventional PPIs. Potassium-competitive acid blockers (P-CABs) were developed and have beneficial effects including rapid, long-lasting, and reversible inhibition of the gastric hydrogen potassium ATPase, the proton pump of the stomach. Vonoprazan was recently innovated as a novel, orally active P-CAB. It is currently indicated for the treatment of gastric and duodenal ulcers, reflux esophagitis, and prevention of low-dose aspirin- or nonsteroidal anti-inflammatory drug-related gastric and duodenal ulcer recurrence in Japan. Vonoprazan does not require enteric coating as it is acid-stable, and it can be taken without food because it is quickly absorbed. Vonoprazan accumulates in parietal cells under both acidic and neutral conditions. It does not require an acidic environment for activation, has long-term stability at the site of action, and has satisfactory safety and tolerability. Thus, vonoprazan may address the unmet medical need for the treatment of acid-related diseases.
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Affiliation(s)
- Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
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Mizokami Y, Oda K, Funao N, Nishimura A, Soen S, Kawai T, Ashida K, Sugano K. Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study. Gut 2018; 67:1042-1051. [PMID: 28988197 PMCID: PMC5969369 DOI: 10.1136/gutjnl-2017-314010] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 09/08/2017] [Accepted: 09/08/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS NCT01452750, NCT01456260; Results.
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Affiliation(s)
- Yuji Mizokami
- Endoscopic Center, University of Tsukuba Hospital, Tsukuba, Japan
| | - Kazunori Oda
- Takeda Development Center, Takeda Pharmaceutical Company Ltd, Osaka, Japan
| | - Nobuo Funao
- Takeda Development Center, Takeda Pharmaceutical Company Ltd, Osaka, Japan
| | - Akira Nishimura
- Takeda Development Center, Takeda Pharmaceutical Company Ltd, Osaka, Japan
| | - Satoshi Soen
- Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan
| | - Takashi Kawai
- Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan
| | - Kiyoshi Ashida
- Department of Gastroenterology, Rakuwakai Otowa Hospital, Kyoto, Japan
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
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12
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Kinoshita Y, Ishimura N, Ishihara S. Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use. J Neurogastroenterol Motil 2018; 24:182-196. [PMID: 29605975 PMCID: PMC5885718 DOI: 10.5056/jnm18001] [Citation(s) in RCA: 142] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 01/28/2018] [Accepted: 02/09/2018] [Indexed: 12/13/2022] Open
Abstract
Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.
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Affiliation(s)
- Yoshikazu Kinoshita
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane,
Japan
| | - Norihisa Ishimura
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane,
Japan
| | - Shunji Ishihara
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane,
Japan
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13
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Wang C, Li Q, Ye P, Zeng S, Li GH, Chen YX, Zhou XJ, Lv NH. Value of Raw Rhubarb Solution in the Precaution of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Patients with High-Risk Factors: A Predictive Random Compared Research in One Center. Dig Dis Sci 2017; 62:1043-1050. [PMID: 28194668 DOI: 10.1007/s10620-017-4464-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 01/16/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIMS Post-ERCP pancreatitis and hyperamylasemia are common complications of endoscopic retrograde cholangiopancreatography (ERCP), especially in high-risk patients. The aim of this study is to evaluate whether a raw rhubarb solution can reduce the incidence of PEP and post-ERCP hyperamylasemia. METHODS From October 2012 to October 2013, 2100 patients received ERCP in our Endoscopic Center. Five hundred patients with high-risk factors were enrolled randomly into the raw rhubarb group (RG, 250 cases drank a raw rhubarb soak solution per 3 h until defecation after ERCP) and the control group (CG, 250 cases drank water after ERCP) in the study. The serum amylase concentration was measured. The abdominal pain, purge time and symptoms of patients were observed in the two groups. RESULTS There were no differences in patient demographics, medical history, ERCP procedure, and patient- and procedure-related high-risk factors between the two groups. PEP incidence was 2% (5/250) in the RG group, which was lower than that in the CG group (7.6%, 19/250) (P < 0.01). The rate of post-ERCP hyperamylasemia was 5.2% (13/250) and 16.8% (42/250) in the RG group and CG group, respectively. The incidence of hyperamylasemia in the RG group was significantly lower than that in the CG group (P < 0.01). The incidence of abdominal pain 24 h after ERCP in the RG group was lower than that in the CG group (P < 0.01). No side effects were observed for raw rhubarb solution. CONCLUSIONS A raw rhubarb solution is safe and effective in preventing the incidence of PEP and hyperamylasemia in high-risk patients.
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Affiliation(s)
- Chong Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Qirui Li
- Medical College of Nanchang University, Nanchang, Jiangxi Province, China
| | - Peng Ye
- Department of Gastroenterology, The People Hospital of Ganzhou City, Ganzhou, Jiangxi Province, China
| | - Sheng Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Guo-Hua Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
| | - You-Xiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Xiao-Jiang Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Nong-Hua Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
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Sakurai Y, Shiino M, Horii S, Okamoto H, Nakamura K, Nishimura A, Sakata Y. Pharmacokinetic Drug-Drug Interactions Between Vonoprazan and Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drugs: A Phase 2, Open-Label, Study in Healthy Japanese Men. Clin Drug Investig 2017; 37:39-49. [PMID: 27581248 PMCID: PMC5209422 DOI: 10.1007/s40261-016-0455-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background Gastroprotective agents are recommended for patients receiving low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs). Vonoprazan is a potassium-competitive acid blocker recently approved for the prevention of peptic ulcer recurrence in patients receiving LDA or NSAIDs. Methods This phase 2, open-label, single-center study in healthy Japanese males evaluated drug–drug interactions between vonoprazan 40 mg and LDA (100 mg) or NSAIDs [loxoprofen sodium (60 mg), diclofenac sodium (25 mg), or meloxicam (10 mg)] and vice versa. Subjects were allocated to one of eight cohorts and received their orally administered treatment regimen (to assess the effect of vonoprazan vs. NSAID or LDA, or vice versa) once daily. Endpoints were the pharmacokinetics of plasma concentrations of the study drugs alone and in combination (primary), safety (secondary), and vonoprazan effects on aspirin-mediated inhibition of platelet-aggregation. Results Of 109 subjects screened, 64 were assigned to one of eight cohorts (n = 8 per cohort) and received treatment, one subject discontinued due to a treatment-emergent adverse event (TEAE), and 63 completed the study. There were few differences in the pharmacokinetics of vonoprazan when administered with LDA or NSAIDs, and few differences in the pharmacokinetics of LDA or NSAIDs when administered with vonoprazan. The differences were small and not clinically meaningful. Inhibition of arachidonic-induced platelet aggregation by LDA was not influenced by vonoprazan. Six patients experienced a TEAE, all were mild and were deemed unrelated to study drugs. One subject withdrew due to infection (tonsillitis). Conclusions No clinically meaningful drug–drug interactions were observed and vonoprazan was well tolerated when administered with LDA or NSAIDs. Study registration JapicCTI-153100 Electronic supplementary material The online version of this article (doi:10.1007/s40261-016-0455-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yuuichi Sakurai
- Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan.
| | - Madoka Shiino
- Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan
| | - Sayako Horii
- Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan
| | - Hiroyuki Okamoto
- Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan
| | - Koki Nakamura
- Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan
| | - Akira Nishimura
- Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan
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Satoh K, Yoshino J, Akamatsu T, Itoh T, Kato M, Kamada T, Takagi A, Chiba T, Nomura S, Mizokami Y, Murakami K, Sakamoto C, Hiraishi H, Ichinose M, Uemura N, Goto H, Joh T, Miwa H, Sugano K, Shimosegawa T. Evidence-based clinical practice guidelines for peptic ulcer disease 2015. J Gastroenterol 2016; 51:177-194. [PMID: 26879862 DOI: 10.1007/s00535-016-1166-4] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Accepted: 01/06/2016] [Indexed: 02/05/2023]
Abstract
The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti-inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID-related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pylori-positive patients with no indication for eradication therapy, non-eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse.
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Affiliation(s)
- Kiichi Satoh
- Department of Gastroenterology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara-shi, Tochigi, 329-2763, Japan.
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan.
| | - Junji Yoshino
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Taiji Akamatsu
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Toshiyuki Itoh
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Mototsugu Kato
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Tomoari Kamada
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Atsushi Takagi
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Toshimi Chiba
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Sachiyo Nomura
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Yuji Mizokami
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Kazunari Murakami
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Choitsu Sakamoto
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Hideyuki Hiraishi
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Masao Ichinose
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Naomi Uemura
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Hidemi Goto
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Takashi Joh
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Hiroto Miwa
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Kentaro Sugano
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for creating and evaluating the "Evidence-based clinical practice guidelines for peptic ulcer", the Japanese Society of Gastroenterology (JSGE), K-18 Building 8F, 8-9-13, Ginza, Chuo, Tokyo, 104-0061, Japan
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Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One 2015; 10:e0128004. [PMID: 26042842 PMCID: PMC4456166 DOI: 10.1371/journal.pone.0128004] [Citation(s) in RCA: 237] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Accepted: 04/21/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults. METHODS We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy. RESULTS Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31). DISCUSSION Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain.
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Affiliation(s)
- Allison A. Lambert
- Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD, United States of America
| | - Jennifer O. Lam
- Department of International Health, Johns Hopkins University, Baltimore, MD, United States of America
| | - Julie J. Paik
- Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, United States of America
| | - Cesar Ugarte-Gil
- Department of International Health, Johns Hopkins University, Baltimore, MD, United States of America
- Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - M. Bradley Drummond
- Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD, United States of America
| | - Trevor A. Crowell
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD, United States of America
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Liu D, Guo M, Hu Y, Liu T, Yan J, Luo Y, Yun M, Yang M, Zhang J, Guo L. Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimulation on the treatment of rheumatoid arthritis with peptic ulcer: a randomized controlled study. J TRADIT CHIN MED 2015; 35:273-80. [PMID: 26237830 DOI: 10.1016/s0254-6272(15)30097-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To observe the efficacy and safety of oral sanhuangwuji powder, anti-rheumatic drugs (ARDs), and ginger-partitioned acupoint stimulation at zusanli (ST 36) on the treatment of rheumatoid arthritis (RA) complicated by peptic ulcer. METHODS This prospective randomized controlled study included 180 eligible inpatients and outpatients randomly assigned to an ARD treatment (n.= 60), ginger-partitioned stimulation (n = 60), or combination treatment (n = 60). Patients assigned to the ARD group were given oral celecoxib, methotrexate, and esomeprazole. Patients assigned to the ginger-partitioned stimulation group were given ginger-partitioned acupoint stimulation at zusanli (ST 36) in addition to the ARDs. Patients in the combination treatment group were given oral sanhuangwuji powder, ginger-partitioned acupoint stimulation at susanli (ST 36), and ARDs. All patients were followed up for 2 months to evaluate clinical effects and safety. The study was registered in the World Health Organization database at the General Hospital of Chengdu Military Area Command Chinese People's Liberation Army (ChiCTR-TCC12002824). RESULTS The combination treatment group had significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal symptom scores, compared with the other groups (P < 0.05). The peptic ulcer healing rate in the combination treatment group was significantly greater than that in the ARD treatment group (χ2= 16.875, P < 0.05) and the ginger-partitioned stimulation group (χ2= 6.171, P < 0.05). CONCLUSION Combination treatment with ginger-partitioned acupoint stimulation at zusanli (ST 36), oral sanhuangwuji powder, and ARDs had a better clinical effect for RA with complicated peptic ulcer, compared with ARD treatmentalone or in combination with ginger-partitioned acupoint stimulation.
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Liu YH, Zhang ZB, Zheng YF, Chen HM, Yu XT, Chen XY, Zhang X, Xie JH, Su ZQ, Feng XX, Zeng HF, Su ZR. Gastroprotective effect of andrographolide sodium bisulfite against indomethacin-induced gastric ulceration in rats. Int Immunopharmacol 2015; 26:384-91. [PMID: 25916678 DOI: 10.1016/j.intimp.2015.04.025] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 04/07/2015] [Accepted: 04/13/2015] [Indexed: 02/07/2023]
Abstract
Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of andrographolide has been shown to possess anti-inflammatory, antipyretic and analgesic activities. However, there is no report on the gastroprotective effect of ASB against indomethacin-induced gastric ulcer. Here we investigated the possible anti-ulcerogenic potential of ASB and the underlying mechanism against indomethacin-induced gastric ulcer in rats. The ulcer area, histopathological assessment, contents of gastric mucosal glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malonaldehyde (MDA) and prostaglandin E2 (PGE2) were examined. In addition, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) mRNA expression and immunohistochemical evaluation of HSP70, Bcl-2 and Bax proteins were also investigated. Results indicated that ASB pre-treatment significantly reduced the ulcer areas induced by indomethacin compared with the vehicle group. The gastric levels of GSH, CAT and SOD were markedly increased by ASB while the level of MDA was decreased. In addition, ASB pretreatment significantly promoted the gastric PGE2 levels and up-regulated the COX-1 and COX-2 mRNA expression in comparison with the vehicle group. Immunohistochemistry analysis showed obvious up-regulation of HSP70 and Bcl-2 protein expression while suppression of Bax protein in the gastric tissue of ASB-pretreated group. Taken together, these findings indicated that the gastroprotective effect of ASB might be associated with the improvement of antioxidative status, activation of COX-mediated PGE2 synthesis, down-regulation of Bax proteins and up-regulation of Bcl-2 and HSP70 proteins. ASB might have the potential for further development as a promising alternative for antiulcer treatment.
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Affiliation(s)
- Yu-Hong Liu
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Zhen-Biao Zhang
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Yi-Feng Zheng
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Hai-Ming Chen
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xiu-Ting Yu
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China
| | - Xiao-Ying Chen
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xie Zhang
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Jian-Hui Xie
- The Second Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China
| | - Zu-Qing Su
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Xue-Xuan Feng
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China
| | - Hui-Fang Zeng
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
| | - Zi-Ren Su
- School of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, PR China.
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Wu LL, Yang YS, Cai FC, Wang SF. Gastric body diaphragm-like stricture as a rare complication of nonsteroidal anti-inflammatory drugs. World J Gastroenterol 2013; 19:3703-3706. [PMID: 23801876 PMCID: PMC3691042 DOI: 10.3748/wjg.v19.i23.3703] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 03/01/2013] [Accepted: 04/04/2013] [Indexed: 02/06/2023] Open
Abstract
Increased risk due to nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been observed in patients. Although diaphragm-like stricture in the small bowel and colon induced by NSAIDs therapy has been rarely reported, gastric body diaphragm-like stricture has not been reported. We describe the first case of gastric body diaphragm-like stricture due to NSAIDs in a 44-year-old male patient who was successfully treated by an endoscopic approach to avoid complicated surgery. This case highlights new insight into the disadvantages of NSAIDs and provides new data for future clinical studies.
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20
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Fei F, Zhou Z. New substituted benzimidazole derivatives: a patent review (2010 – 2012). Expert Opin Ther Pat 2013; 23:1157-79. [DOI: 10.1517/13543776.2013.800857] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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21
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Sugano K, Kinoshita Y, Miwa H, Takeuchi T. Safety and efficacy of long-term esomeprazole 20 mg in Japanese patients with a history of peptic ulcer receiving daily non-steroidal anti-inflammatory drugs. BMC Gastroenterol 2013; 13:54. [PMID: 23530709 PMCID: PMC3623652 DOI: 10.1186/1471-230x-13-54] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2012] [Accepted: 03/18/2013] [Indexed: 12/26/2022] Open
Abstract
Background Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan. Methods This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive. Results A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year. Conclusion Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer. Trial registration ClinicalTrials.gov identifier NCT00595517.
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Affiliation(s)
- Kentaro Sugano
- Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
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22
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Adherence to the preventive strategies for nonsteroidal anti-inflammatory drug- or low-dose aspirin-induced gastrointestinal injuries. J Gastroenterol 2013; 48:559-73. [PMID: 23460386 PMCID: PMC3654181 DOI: 10.1007/s00535-013-0771-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 01/30/2013] [Indexed: 02/04/2023]
Abstract
As the aging of the population advances, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or low-dose aspirin (LDA) is increasing. Their use is accompanied by a risk of serious complications, such as hemorrhage or perforation of the gastrointestinal tract. Therefore, gastroprotective strategies upon the prescription of NSAIDs/LDA are outlined in several guidelines or recommendations. Because all NSAIDs including cyclooxygenase (COX)-2 inhibitors have cardiovascular (CV) toxicity, recent guidelines are based on not only GI risks but also CV risks of NSAID users. Assessment of the adherence to evidence-based guidelines or recommendations for the safe prescription of NSAIDs/LDA in clinical practice is an important issue. Here, we summarize randomized controlled trials (RCTs) on the preventive effects of antisecretory drugs for NSAID- or LDA-induced peptic ulcers. Then, we describe preventive strategies upon the prescription of NSAIDs/LDA outlined in several guidelines or recommendations, and describe studies on adherence and outcomes of adherence to these preventive strategies. Finally, we discuss strategies to increase the adherence rate, and changing pattern of GI events associated with NSAIDs/LDA. In Japan, the preventive strategies upon the prescription of NSAIDs/LDA are expected to spread rapidly because the use of proton pump inhibitors for the prevention of recurrence of NSAID- or LDA-induced peptic ulcers and the use of COX-2 for the palliation of acute pain were recently approved under the national health insurance system. Further studies on adherence to the preventive strategies and the outcomes of adherence, which include both GI events and CV events, in the Japanese population are required.
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23
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Sugano K, Kinoshita Y, Miwa H, Takeuchi T. Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti-inflammatory drug-related peptic ulcers in Japanese patients. Aliment Pharmacol Ther 2012; 36:115-25. [PMID: 22591121 DOI: 10.1111/j.1365-2036.2012.05133.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 03/06/2012] [Accepted: 04/24/2012] [Indexed: 12/30/2022]
Abstract
BACKGROUND The use of proton pump inhibitors for prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse events is well documented. However, data regarding the efficacy and safety of this approach in Japan are scarce. AIM To evaluate the efficacy and tolerability of esomeprazole in preventing NSAID-induced peptic ulcers in Japanese at-risk patients. METHODS Male and female Japanese adult patients (aged ≥ 20 years) with endoscopically confirmed history of peptic ulcers who required long-term oral NSAID therapy for a chronic inflammatory condition were randomised to 24 weeks' treatment with esomeprazole 20 mg once daily or matching placebo. The primary end point was the Kaplan-Meier estimated proportion of ulcer-free patients. RESULTS Overall, 343 patients were randomised to treatment (esomeprazole, n = 175; placebo, n = 168). The Kaplan-Meier estimated ulcer-free rate over the 24-week treatment period was significantly higher (log-rank P < 0.001) in esomeprazole-treated patients (96.0%; 95% CI 92.8, 99.1) than in placebo recipients (64.4%; 95% CI 56.8, 71.9). Esomeprazole was effective at preventing peptic ulcers in both Helicobacter pylori-positive and -negative patients (96.3% vs. 95.5% of patients ulcer-free, respectively); however, in the placebo group, the proportion of ulcer-free patients at 24 weeks was markedly lower among H. pylori-positive than -negative patients (59.7% vs. 69.9%). The NSAID type did not seem to affect the estimated ulcer-free rate with esomeprazole. Treatment with esomeprazole was well tolerated. CONCLUSION Esomeprazole 20 mg once daily is effective and safe in preventing ulcer recurrence in Japanese patients with a definite history of peptic ulcers who were taking an NSAID (ClinicalTrials.gov identifier: NCT00542789).
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Affiliation(s)
- K Sugano
- Department of Medicine, Jichi Medical University, Shimotsuke, Japan
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Seo KA, Lee SJ, Kim KB, Bae SK, Liu KH, Kim DH, Shin JG. Ilaprazole, a new proton pump inhibitor, is primarily metabolized to ilaprazole sulfone by CYP3A4 and 3A5. Expert Opin Ther Pat 2011. [PMID: 22022918 DOI: 10.1517/13543776.2013.741121] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Ilaprazole is a new proton pump inhibitor, designed for treatment of gastric ulcers, and developed by Il-Yang Pharmaceutical Co (Seoul, Korea). It is extensively metabolised to the major metabolite ilaprazole sulfone. In the present study, several in vitro approaches were used to identify the cytochrome P450 (CYP) enzymes responsible for ilaprazole sulfone formation. Concentrations of ilaprazole sulfone were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Incubation of ilaprazole with cDNA-expressed recombinant CYPs indicated that CYP3A was the major enzyme that catalyses ilaprozole to ilaprazole sulfone. This reaction was inhibited significantly by ketoconazole, a CYP3A inhibitor, and azamulin, a mechanism-based inhibitor of CYP3A, while no substantial effect was observed using selective inhibitors for eight other P450s (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1). In addition, the formation of ilaprazole sulfone correlated well with CYP3A-catalysed testosterone 6β-hydroxylation and midazolam 1'-hydroxylation in 20 different human liver microsome panels. The intrinsic clearance of the formation of ilaprazole sulfone by CYP3A4 was 16-fold higher than that by CYP3A5. Collectively, these results indicate that the formation of the major metabolite of ilaprazole, ilaprazole sulfone, is predominantly catalysed by CYP3A4/5.
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Affiliation(s)
- Kyung-Ah Seo
- Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea
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