{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:08:13Z","timestamp":1767841693332,"version":"3.49.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013207","name":"Reckitt Benckiser Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013207","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Oral non-steroidal anti-inflammatory drugs (NSAIDs) are known to be associated with an increased risk of bleeding. The NSAID, flurbiprofen, in the form of 8.75\u00a0mg lozenge or oromucosal spray is indicated for the symptomatic relief of sore throat. Despite the low dose as compared to alternative flurbiprofen preparations, concerns have been raised regarding its safety in terms of haemorrhagic events. This systematic review was conducted to identify existing evidence on the risk of haemorrhagic events with flurbiprofen 8.75\u00a0mg dose (any formulation), particularly where this may be due to potential interactions with other medicinal products. The systematic review examined studies reporting haemorrhagic events in patients receiving flurbiprofen 8.75\u00a0mg dose. Six individual electronic databases were searched up to 28th April 2020. Records were initially screened for relevance followed by further review of potentially eligible studies. Data extraction was performed for eligible studies and risk of bias in studies was assessed. The search strategy identified 1093 individual records. Of these, 1038 records were excluded after initial review; the majority of these records related to flurbiprofen in alternative formulations with alternative doses (e.g., eye drops, skin patches, oral tablets) thus were not considered relevant for further review. The 55 remaining records related to flurbiprofen 8.75\u00a0mg dose (any formulation) or flurbiprofen lozenge\/oromucosal spray where the dose was not specified. After further review, 52 of these records were not considered eligible. Thus, only three records were included in this systematic review. The three studies reported a total of five haemorrhagic events in patients taking flurbiprofen 8.75\u00a0mg lozenge; the corresponding risk in each of the studies was 8.33, 1.98 and 1.96%. Where possible, comparison of flurbiprofen 8.75\u00a0mg lozenge to placebo produced risk ratios of 0.96 (95% CI 0.07, 13.25) and 2.00 (95% CI 0.10, 118.0). This systematic review found limited evidence on the risk of haemorrhagic events with flurbiprofen when used at a dose of 8.75\u00a0mg. Counts were low across all studies and results comparing flurbiprofen and placebo treatment arms were non-significant. However, scarcity of studies and low certainty of evidence for the outcome of haemorrhagic events limits the conclusions of this systematic review.<\/jats:p>","DOI":"10.3389\/fphar.2021.726141","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T05:54:43Z","timestamp":1628056483000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["A Systematic Review of Flurbiprofen 8.75\u00a0mg Dose and Risk of Haemorrhagic Events"],"prefix":"10.3389","volume":"12","author":[{"given":"Sandeep","family":"Dhanda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Evans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debabrata","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicki","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Townsley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gra\u00e7a","family":"Coutinho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuradha","family":"Kulasekaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Shakir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.jclinepi.2010.07.015","article-title":"Grade Guidelines: 3. Rating the Quality of Evidence","volume":"64","author":"Balshem","year":"2011","journal-title":"J. Clin. Epidemiol."},{"key":"B2","unstructured":"Nct01048866. A Repeat-Dose, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Study to Determine the Safety and Efficacy of Flurbiprofen 8.75mg Lozenge Compared to its Vehicle Control Lozenge in Patients with Painful Pharyngitis"},{"key":"B3","volume-title":"Nct01049334. A Randomized, Double-Blind, Placebo-Controlled Multiple-Dose Study to Determine the Efficacy, Onset, and Duration of Action of Flurbiprofen 8.75 Mg Lozenge Compared to its Vehicle Control Lozenge in Patients with Painful Pharyngitis","year":""},{"key":"B4","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1177\/0091270004265703","article-title":"Analgesic Effect of Sustained-Release Flurbiprofen Administered at the Site of Tissue Injury in the Oral Surgery Model","volume":"44","author":"Dionne","year":"2004","journal-title":"J. Clin. Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"E006245","DOI":"10.1136\/bmjopen-2014-006245","article-title":"Continued High Rates of Antibiotic Prescribing to Adults with Respiratory Tract Infection: Survey of 568 Uk General Practices","volume":"4","author":"Gulliford","year":"2014","journal-title":"Bmj Open"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1002\/9781119536604","volume-title":"Cochrane Handbook for Systematic Review of Interventions","author":"Higgins","year":"2019"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1002\/jper.17-0381","article-title":"Oral Flurbiprofen Spray for Mucosal Graft Harvesting at the Palatal Area: A Randomized Placebo-Controlled Study","volume":"89","author":"Isler","year":"2018","journal-title":"J. Periodontol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"B2700","DOI":"10.1136\/bmj.b2700","article-title":"The Prisma Statement for Reporting Systematic Reviews and Meta-Analyses of Studies that Evaluate Healthcare Interventions: Explanation and Elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"Bmj"},{"key":"B9","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1159\/000336767","article-title":"A Randomised, Two-Period, Cross-Over, Open-Label Study to Evaluate the Pharmacokinetic Profiles of Single Doses of Two Different Flurbiprofen 8.75-Mg Lozenges in Healthy Volunteers","volume":"89","author":"Matzneller","year":"2012","journal-title":"Pharmacology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.2147\/TCRM.S79135","article-title":"Adverse Drug Reactions and Drug-Drug Interactions with Over-the-counter Nsaids","volume":"11","author":"Moore","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"key":"B11","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1136\/bmjebm-2017-110853","article-title":"Methodological Quality and Synthesis of Case Series and Case Reports","volume":"23","author":"Murad","year":"2018","journal-title":"Bmj Ebm"},{"key":"B12","volume-title":"Nice Guideline [Ng84]. Sore Throat (Acute): Antimicrobial Prescribing","year":"2018"},{"key":"B13","doi-asserted-by":"publisher","first-page":"N71","DOI":"10.1136\/bmj.n71","article-title":"The Prisma 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"Bmj"},{"key":"B14","doi-asserted-by":"publisher","first-page":"81s","DOI":"10.18433\/j3t886","article-title":"Evolution of Nonsteroidal Anti-inflammatory Drugs (Nsaids): Cyclooxygenase (Cox) Inhibition and beyond","volume":"11","author":"Rao","year":"2008","journal-title":"J. Pharm. Pharm. Sci."},{"key":"B15","article-title":"Summary of Product Characteristics","year":"2016"},{"key":"B16","article-title":"Summary of Product Characteristics","volume":"8","year":"2018","journal-title":"Strefen Direct"},{"key":"B17","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/atvbaha.110.207449","article-title":"Prostaglandins and Inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Atvb"},{"key":"B18","doi-asserted-by":"publisher","first-page":"L4898","DOI":"10.1136\/bmj.l4898","article-title":"Rob 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials","volume":"366","author":"Sterne","year":"2019","journal-title":"Bmj"},{"key":"B19","doi-asserted-by":"publisher","first-page":"I4919","DOI":"10.1136\/bmj.i4919","article-title":"Robins-I: A Tool for Assessing Risk of Bias in Non-randomised Studies of Interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"Bmj"},{"key":"B20","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1111\/coa.13058","article-title":"The Effect of Flurbiprofen Oral Spray and Ibuprofen vs Ibuprofen Alone on Postoperative Tonsillectomy Pain: An Open, Randomised, Controlled Trial","volume":"43","author":"T\u00fcrk","year":"2018","journal-title":"Clin. Otolaryngol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.726141\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T05:54:47Z","timestamp":1628056487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.726141\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,4]]},"references-count":20,"alternative-id":["10.3389\/fphar.2021.726141"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.726141","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,4]]},"article-number":"726141"}}