High Economic Burden Yet Low Clinical Value: Why is So Much Sucralfate Prescribed?

High Economic Burden Yet Low Clinical Value: Why is So Much Sucralfate Prescribed? | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Basic & Clinical Pharmacology & Toxicology This is a preprint and has not been peer reviewed. Data may be preliminary. 31 March 2025 V1 Latest version Share on High Economic Burden Yet Low Clinical Value: Why is So Much Sucralfate Prescribed? Authors : Neha Wadhavkar 0000-0002-1084-304X [email protected] , Laura Varnum , and Steven F. Moss Authors Info & Affiliations https://doi.org/10.22541/au.174342434.45470421/v1 Published Basic & Clinical Pharmacology & Toxicology Version of record Peer review timeline 627 views 286 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Sucralfate is a commonly prescribed medication in use for decades. Despite the availability of more effective medications for acid-dyspeptic conditions, including proton pump inhibitors and histamine H2-receptor antagonists, sucralfate continues to be utilized for upper gastrointestinal symptoms. We reviewed the limited evidence base supporting the approval and ongoing usage of sucralfate and performed a cost analysis using the ClinCalc database. The financial impact of sucralfate was comparable to famotidine, lansoprazole, and ranitidine. We encourage further studies to accurately gauge the true clinical efficacy of sucralfate and to question its ongoing prescription until then. High Economic Burden Yet Low Clinical Value: Why is So Much Sucralfate Prescribed? Neha Wadhavkar, MD 1 , Laura Varnum, PharmD 2 , Steven F. Moss, MD 3 1 Department of Internal Medicine, Brown University, Providence, RI 2 Lifespan Specialty Pharmacy, Providence, RI 3 Division of Gastroenterology, Brown University, Providence, RI Conflicts of Interest: SFM: Consultant to Phathom Pharmaceuticals, American Molecular Labs, Redhill Biopharma, Meridian Biosciences. Other authors disclose no conflicts. Author Contributions: NW: Conception, design, literature review, writing, editing. LV: Literature review, editing. SM: Conception, design, editing. Financial Disclosures: None Corresponding author: Neha Wadhavkar Address for Correspondence: Neha Wadhavkar, MD. Rhode Island Hospital, Dept Internal Medicine, 593 Eddy St, Providence, RI 02903 Telephone number: 401-444-7474 e-mail address: [email protected] Co-author email addresses: [email protected] | [email protected] Word Count: 1,127 Key Words: Functional Dyspepsia, GERD, Peptic Ulcer Disease, Clinical Pharmacology, Health Economics Abstract Sucralfate is a commonly prescribed medication in use for decades. Despite the availability of more effective medications for acid-dyspeptic conditions, including proton pump inhibitors and histamine H2-receptor antagonists, sucralfate continues to be utilized for upper gastrointestinal symptoms. We reviewed the limited evidence base supporting the approval and ongoing usage of sucralfate and performed a cost analysis using the ClinCalc database. The financial impact of sucralfate was comparable to famotidine, lansoprazole, and ranitidine. We encourage further studies to accurately gauge the true clinical efficacy of sucralfate and to question its ongoing prescription until then. Introduction and Background Sucralfate is a commonly prescribed medication that has been widely used for several decades since its first development in Japan in the 1960s. 1 Though the exact mechanism of action is not well understood, it is thought to act as a mucosal protectant against gastric acid and pepsin, with the aluminum salt binding to positively charged proteins to create a thick, viscous ulcer-adherent complex. 2 Sucralfate has an onset of action of 1-2 hours, duration of action up to 6 hours, and is primarily excreted in the feces within 48 hours. 2 Sucralfate is well-tolerated, remaining largely unabsorbed systemically and with little toxicity. 1-3 The tablet form of sucralfate was approved by the Food & Drug Administration (FDA) in 1981, and the oral suspension in 1993. 1,2 Sucralfate was specifically approved for the short-term treatment of active duodenal ulcers for up to 8 weeks. 1-3 First-generation histamine receptor antagonists (H2RAs) were approved around the same time (cimetidine in 1977 and ranitidine in 1981). 1,4 Sucralfate 1g four times daily was found to be superior to placebo for acute duodenal ulcer healing and recurrence prevention by approximately 10-20% at both 4 and 8 weeks. 1,3 The double-blind placebo-controlled trials that are cited in the FDA approval contain few methodological details and with follow-up only to one year. Moreover, none take H. pylori infection and treatment into account. Sucralfate is commonly used off-label, both alone and as an adjunct for other upper gastrointestinal conditions, including gastric ulcers, non-ulcer or functional dyspepsia, and reflux esophagitis. 1,2,5-7 Studies from the 1980s reported similar efficacy for gastric ulcer healing between sucralfate and H2RAs, though studies after 2000 observed no difference between sucralfate and placebo. 1,4,5 Similarly, for non-ulcer dyspepsia, recent reviews concluded that sucralfate was not superior to placebo [unlike prokinetic agents, H2RAs, and proton pump inhibitors (PPIs)]. 5 Additionally, double-blind, randomized controlled trials found no difference between sucralfate and placebo for healing of erosive esophagitis or endoscopic “gastritis.” 6-7 The 2022 American College of Gastroenterology (ACG) guidelines on reflux disease state: “we do not recommend sucralfate for therapy except during pregnancy,” a strong recommendation with low level of evidence. 8 Finally, there are case studies and series that have described the efficacy of sucralfate in stress ulcer prophylaxis and radiation proctitis, which are also off-label uses. 1-2 Given the absence of robust clinical data supporting the use of sucralfate and its ongoing common use in practice, we performed a cost analysis to review the total financial impact of its prescription, in comparison to PPIs and H2RAs. Materials and Methods We reviewed the most recent publicly available pharmacologic data in the United States from 2013 to 2021 on the ClinCalc database. 9 Among the top 200 medications prescribed overall, there were 7 medications used for upper gastrointestinal conditions, including four PPIs (omeprazole, lansoprazole, esomeprazole and pantoprazole), two H2RAs (famotidine and ranitidine), and sucralfate. Data for ranitidine was only available through 2020 due to its recall related to concerns over carcinogenicity. We subsequently used this data to investigate trends in utilization and aggregate costs for sucralfate in comparison to the other medications. Specifically, we analyzed total number of prescriptions (in millions USD) between 2013 and 2021, price per prescription for a 30-day supply (in USD), and total annual cost (in millions USD). The study was conducted in accordance with the Basic & Clinical Pharmacology & Toxicology policy for experimental and clinical studies [11]. Results From 2013 to 2021, there was a slight increase in the total annual number of sucralfate prescriptions from 1.8 to 2.6 million (Figure 1). The use of famotidine increased from 4.9 to 11.7 million, whereas ranitidine decreased drastically after 2018 from its peak of 19 million. Omeprazole was the most prescribed medication, though from 2016 to 2021, number of prescriptions declined from 75 to 54 million. Lansoprazole and esomeprazole prescription also drastically declined between 2013 and 2021 (6.3 to 1.9 million and 18 to 4.7 million, respectively). Regarding cost per prescription, sucralfate was second behind esomeprazole for most expensive ($119 versus $195), followed by lansoprazole at $70 (Figure 2A). The least expensive were ranitidine ($16) and omeprazole ($17). Finally, when looking at total annual cost, the three PPIs had the highest cost (Figure 2B). Pantoprazole incurred the highest cost at over $1 billion ($1,000,371,111), and both omeprazole and esomeprazole were over $900 million ($928,644,712 and $911,416,545, respectively). The total annual cost of sucralfate was $312,410,458, which was higher than that of famotidine, lansoprazole, and ranitidine ($291,117,773, $138,261,407, and $51,313,203, respectively). Discussion We found that financial expenditure on sucralfate is comparable to PPIs and H2RAs, despite the paucity of clinical data justifying its usage. Sucralfate is the second most expensive gastroenterological medication based on cost per prescription and had a total annual cost approximately $20 million higher than famotidine and $174 million higher than lansoprazole. Of note, sucralfate is only available by prescription and its actual wholesale price is $7.30 per 1mL of oral suspension and $0.38 per tablet. 9 Famotidine remains the primary H2RA currently available, we suspect largely due to ranitidine’s recall in 2020. As expected, we found that PPIs are widely prescribed and have had a consistently significant financial impact over the past decade. However, we observed decreased PPI utilization in the recent years. This may in part be due to increased over the counter purchases which are not captured by the ClinCalc database. Decreased PPI prescription may also reflect recent negative media on possible long-term negative health effects related to chronic PPI usage. 10 We suspect that PPI usage will continue to decline in coming years over these concerns, and that more patients and providers may turn to alternatives, including sucralfate and famotidine. We hypothesize that our findings may in part be due to providers seeking out alternative therapy after exhausting PPIs or H2RAs for patients with upper gastrointestinal symptoms, such as functional dyspepsia or reflux, and may opt for sucralfate given the little associated harm despite the absence of clinical data. Limitations of this study are that ClinCalc cannot capture non-prescription and over-the-counter usage of PPIs and H2RAs, which may cause an overestimate of sucralfate usage. Furthermore, the database cannot provide insight into the indications for prescription, whether sucralfate is prescribed as monotherapy or adjunct therapy, or the clinical setting of prescription (i.e. outpatient versus inpatient), which may guide future prospective studies in further clarifying the clinical efficacy of sucralfate. Other future directions may include increasing generalizability by assessing trends in sucralfate prescription in other countries and how they compare to the those in the United States. In conclusion, sucralfate is commonly prescribed, despite the absence of robust or recent data to support its use. Sucralfate has a considerable financial impact, similar to PPIs and H2RAs, both of which have a large evidence base to support their use for various gastroenterological conditions. Without high quality clinical evidence to justify the use of sucralfate, providers and patients should question the ongoing prescription of this expensive medication until future studies are pursued. Acknowledgements None. References 1. Sucralfate. Richardson CT. Ann Intern Med. 1982 Aug;97(2):269-72. doi: 10.7326/0003-4819-97-2-269. PMID: 6896615. 2. Kudaravalli P, John S. Sucralfate. [Updated 2022 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551527/ 3. Department of Health and Human Services. (2017, July). Carafate® (sucralfate) oral suspension - accessdata.fda.gov . The United States Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019183s019lbl.pdf 4. Sucralfate. A review of its pharmacodynamic properties and therapeutic use in peptic ulcer disease. Brogden RN, Heel RC, Speight TM, Avery GS. Drugs. 1984 Mar;27(3):194-209. doi: 10.2165/00003495-198427030-00002. PMID: 6368184. 5. Garnett WR. Sucralfate–alternative therapy for peptic-ulcer disease. Clin Pharm. 1982 Jul-Aug;1(4):307-14. PMID: 6764389. 6. Robert M. Williams, Roy C. Orlando, Eugene M. Boyzmski, Randy D. Readling, Donald O. Castell, Walter M. Roufail, Gregory G. Rick, Steven E. Rubin, Dennis R. Sinar. Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis. The American Journal of Medicine. Volume 83, Issue 3, Supplement 2. 1987. Pages 61-66. ISSN 0002-9343. https://doi.org/10.1016/0002-9343(87)90830-8. 7. Skoubo-Kristensen E, Funch-Jensen P, Kruse A, Hanberg-Sørensen F, Amdrup E. Controlled clinical trial with sucralfate in the treatment of macroscopic gastritis. Scand J Gastroenterol. 1989 Aug;24(6):716-20. doi: 10.3109/00365528909093113. PMID: 2683019. 8. Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. doi: 10.14309/ajg.0000000000001538. PMID: 34807007; PMCID: PMC8754510. 9. Sean P. Kane, P. (2022). The Top 200 Drugs of 2021 . ClinCalc. https://clincalc.com/DrugStats/Top200Drugs.aspx 10. Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2018 Nov 19;10:2042098618809927. doi: 10.1177/2042098618809927. PMID: 31019676; PMCID: PMC6463334. 11. Tveden-Nyborg P, Bergmann TK, Jessen N, Simonsen U, Lykkesfeldt J. BCPT 2023 policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol. 2023;133:391-396 Figure 1. Total number of prescriptions for common upper gastrointestinal medications from 2013 to 2021. Figure 2A. Cost per prescription for a 30-day supply of common upper gastrointestinal medications in 2021. Figure 2B. Total annual cost of common upper gastrointestinal medications in 2021 (*for ranitidine, only 2020 data available, due to recall). Information & Authors Information Version history V1 Version 1 31 March 2025 Peer review timeline Published Basic & Clinical Pharmacology & Toxicology Version of Record 13 Jun 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Basic & Clinical Pharmacology & Toxicology Authors Affiliations Neha Wadhavkar 0000-0002-1084-304X [email protected] Brown University View all articles by this author Laura Varnum Brown University View all articles by this author Steven F. Moss Brown University View all articles by this author Metrics & Citations Metrics Article Usage 627 views 286 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Neha Wadhavkar, Laura Varnum, Steven F. Moss. High Economic Burden Yet Low Clinical Value: Why is So Much Sucralfate Prescribed?. Authorea . 31 March 2025. DOI: https://doi.org/10.22541/au.174342434.45470421/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.174342434.45470421/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9febefcf9da409d6',t:'MTc3OTI4NjM1MQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();