{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:49:46Z","timestamp":1792100986001,"version":"4.4.0"},"reference-count":64,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>EA 575, the ivy leaf dry extract of the herbal medicine Prospan, has been widely used for the management of cough associated with various respiratory conditions. Over the past decade, new evidence has emerged from interventional and non-interventional studies offering a more comprehensive understanding of its efficacy, safety, and tolerability. This review provides an updated synthesis of clinical evidence of EA\u2009575 in pediatric and adult patients with respiratory disease. A total of 27 publications were included, covering 13 interventional trials, 13 non-interventional studies, and 1 meta-analysis. These studies collectively enrolled 102\u200a239 patients, of whom 84\u200a022 received EA 575 treatment. The findings consistently demonstrate that EA 575 improves cough symptoms and lung function, as shown by improvements in the Bronchitis Severity Score, spirometry, and body plethysmography, depending on the parameters that have been assessed. Moreover, the tolerability of EA 575 has been increasingly confirmed through large real-world evidence studies that report a low number of non-serious adverse events. These results reinforce the well-established role of EA 575 in the effective and safe treatment of cough in clinical practice.<\/jats:p>","DOI":"10.1055\/a-2745-1130","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T23:42:26Z","timestamp":1769211746000},"page":"774-789","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Safety of Ivy Leaf Dry Extract EA 575 in Cough Management: An Updated Review of Clinical Evidence"],"prefix":"10.1055","volume":"92","author":[{"given":"Inga","family":"Trompetter","sequence":"additional","affiliation":[{"name":"Engelhard Arzneimittel GmbH & Co. KG, Niederdorfelden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1518-4174","authenticated-orcid":false,"given":"Simon","family":"Braun","sequence":"additional","affiliation":[{"name":"Engelhard Arzneimittel GmbH & Co. KG, Niederdorfelden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12875-021-01501-0","article-title":"Prevalence, aetiologies and prognosis of the symptom cough in primary care: A systematic review and meta-analysis","volume":"22","author":"M Bergmann","year":"2021","journal-title":"BMC Fam Pract"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1471-2296-9-10","article-title":"Measuring the financial burden of acute cough in pre-school children: A cost of illness study","volume":"9","author":"S Hollinghurst","year":"2008","journal-title":"BMC Fam Pract"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1185\/03007995.2015.1062355","article-title":"Impact of cough and common cold on productivity, absenteeism, and daily life in the United States: ACHOO survey","volume":"31","author":"P V Dicpinigaitis","year":"2015","journal-title":"Curr Med Res Opin"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1080\/03007995.2021.1982685","article-title":"The financial burden of treating patients presenting with acute and chronic cough","volume":"37","author":"S S Birring","year":"2021","journal-title":"Curr Med Res Opin"},{"key":"ref5","volume-title":"Cough","author":"S Sharma","year":"2023"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1128\/jcm.35.11.2864-2868.1997","article-title":"Frequency and natural history of rhinovirus infections in adults during autumn","volume":"35","author":"E Arruda","year":"1997","journal-title":"J Clin Microbiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1590\/0074-02760150154","article-title":"Viral aetiology of common colds of outpatient children at primary care level and the use of antibiotics","volume":"110","author":"J Kamikawa","year":"2015","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"518","DOI":"10.3390\/children12040518","article-title":"The impact of ivy leaf dry extract EA 575 on subsequent antibiotic use and its therapeutic value in children and adolescents with the common cold: A retrospective prescription database analysis","volume":"12","author":"C Vogelberg","year":"2025","journal-title":"Children"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"c2096","DOI":"10.1136\/bmj.c2096","article-title":"Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: Systematic review and meta-analysis","volume":"340","author":"C Costelloe","year":"2010","journal-title":"BMJ"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.aimed.2020.07.012","article-title":"The effects of Hedera Helix on viral respiratory infections in humans: A rapid review","volume":"7","author":"L A Barnes","year":"2020","journal-title":"Adv Integr Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1055\/s-0035-1545879","article-title":"A valuable option for the treatment of respiratory diseases: Review on the clinical evidence of the ivy leaves dry extract EA 575","volume":"81","author":"C Lang","year":"2015","journal-title":"Planta Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1055\/s-0035-1565974","article-title":"Efeu in der p\u00e4diatrischen Praxis: Anwendung von EA 575 in der Therapie der akuten Bronchitis bei Schulkindern","volume":"36","author":"C Lang","year":"2015","journal-title":"Z Phytother"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"105939","DOI":"10.1016\/j.rmed.2020.105939","article-title":"German respiratory society guidelines for diagnosis and treatment of adults suffering from acute, subacute and chronic cough","volume":"170","author":"P Kardos","year":"2020","journal-title":"Respir Med"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1055\/a-2550-3738","article-title":"S2\u2009k-Leitlinie Fach\u00e4rztliche Diagnostik und Therapie von erwachsenen Patienten mit Husten","volume":"79","author":"P Kardos","year":"2025","journal-title":"Pneumologie"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.pupt.2014.09.002","article-title":"A systematic study on the influence of the main ingredients of an ivy leaves dry extract on the \u03922-adrenergic responsiveness of human airway smooth muscle cells","volume":"31","author":"C Greunke","year":"2015","journal-title":"Pulm Pharmacol Ther"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10787-018-0494-9","article-title":"Anti-inflammatory effects of ivy leaves dry extract: Influence on transcriptional activity of NF\u03baB","volume":"27","author":"J Schulte-Michels","year":"2019","journal-title":"Inflammopharmacology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"6190","DOI":"10.1021\/bi035928t","article-title":"Dynamics of beta2-adrenergic receptor\u2212ligand complexes on living cells","volume":"43","author":"O Hegener","year":"2004","journal-title":"Biochemistry"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1021\/bi802036b","article-title":"\u03b1-hederin, but not hederacoside C and hederagenin from Hedera Helix, affects the binding behavior, dynamics, and regulation of \u03922-adrenergic receptors","volume":"48","author":"A Sieben","year":"2009","journal-title":"Biochemistry"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.phymed.2010.05.010","article-title":"Pre-treatment with \u03b1-hederin increases \u03b2-adrenoceptor mediated relaxation of airway smooth muscle","volume":"18","author":"A Wolf","year":"2011","journal-title":"Phytomedicine"},{"key":"ref21","first-page":"19","article-title":"In vitro studies: An article on the mechanism of action of ivy","volume":"150","author":"F Runkel","year":"2005","journal-title":"Pharm Ztg"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"153645","DOI":"10.1016\/j.phymed.2021.153645","article-title":"Ivy leaves dry extract EA 575 mediates biased \u03922-adrenergic receptor signaling","volume":"90","author":"F Meurer","year":"2021","journal-title":"Phytomedicine"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.3390\/biomedicines13071673","article-title":"Efficacy of EA575 as an antitussive and mucoactive agent in preclinical in vivo models","volume":"13","author":"M Hufnagel","year":"2025","journal-title":"Biomedicines"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1080\/03007995.2023.2258777","article-title":"Ivy leaf dry extract EA 575 for the treatment of acute and chronic cough in pediatric patients: Review and expert survey","volume":"39","author":"G Seifert","year":"2023","journal-title":"Curr Med Res Opin"},{"key":"ref26","first-page":"26","article-title":"Therapie des Asthma Bronchiale mit Efeubl\u00e4tter-Trockenextrakt","volume":"14","author":"H J Mansfeld","year":"1998","journal-title":"Munch Med Wochenschr"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.phymed.2014.05.006","article-title":"Tolerance and effect of an add-on treatment with a cough medicine containing ivy leaves dry extract on lung function in children with bronchial asthma","volume":"21","author":"S Zeil","year":"2014","journal-title":"Phytomedicine"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"504","DOI":"10.31083\/ph.2016.6712","article-title":"A randomized, controlled, double-blind, multi-center trial to evaluate the efficacy and safety of a liquid containing ivy leaves dry extract (EA 575) vs. placebo in the treatment of adults with acute cough","volume":"9","author":"A Schaefer","year":"2016","journal-title":"Pharmazie"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"00019","DOI":"10.1183\/23120541.00019-2019","article-title":"Efficacy of two dosing schemes of a liquid containing ivy leaves dry extract EA 575 versus placebo in the treatment of acute bronchitis in adults","volume":"5","author":"A Schaefer","year":"2019","journal-title":"ERJ Open Res"},{"key":"ref30","first-page":"61","article-title":"Efeu versus Ambroxol bei Chronischer Bronchitis","volume":"69","author":"J Meyer-Wegener","year":"1993","journal-title":"Z Allg Med"},{"key":"ref31","first-page":"291","article-title":"Consequent therapy of chronic obstructive respiratory tract illnesses in children","volume":"5","author":"A Gulyas","year":"1997","journal-title":"Atemw Lungenkrkh"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.phymed.2011.06.014","article-title":"Acute bronchitis therapy with ivy leaves extracts in a two-arm study. A double-blind, randomised study vs. an other ivy leaves extract","volume":"18","author":"U Cwientzek","year":"2011","journal-title":"Phytomedicine"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"754","DOI":"10.3390\/ph18050754","article-title":"Efficacy and safety of a single ivy extract versus two herbal extract combinations in patients with acute bronchitis: A multi-center, randomized, open-label clinical trial","volume":"18","author":"P Kardos","year":"2025","journal-title":"Pharmaceuticals"},{"key":"ref34","first-page":"155","article-title":"Sekretolyse und Bronchospasmolyse","volume":"10","author":"H J Mansfeld","year":"1997","journal-title":"TW P\u00e4diatr"},{"key":"ref35","first-page":"1","article-title":"Bronchitis bei Kindern: Klinische Studie mit Efeubl\u00e4tter-Trockenextrakt","volume":"4","author":"M Unkauf","year":"2000","journal-title":"Bayer Internist"},{"key":"ref37","first-page":"1","article-title":"Efficacy of prospan application in children\u02bcs diseases of respiratory tract","volume":"4","author":"V Maidannik","year":"2003","journal-title":"Pediatr Tocol Gynecol"},{"key":"ref38","first-page":"1","article-title":"Comparing the efficacy and safety of high-concentrate (5\u20137.5: 1) ivy leaves extract and acetylcysteine for treatment of children with acute bronchitis","volume":"11","author":"Y Bolbot","year":"2004","journal-title":"Drugs Ukr"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1055\/s-0034-1377332","article-title":"Assessment of the effect of pharmacotherapy in common cold\/acute bronchitis \u2013 the Bronchitis Severity Scale (BSS)","volume":"68","author":"P Kardos","year":"2014","journal-title":"Pneumologie"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"20041","DOI":"10.1038\/s41598-022-24393-1","article-title":"Ivy leaves extract EA 575 in the treatment of cough during acute respiratory tract infections: Meta-analysis of double-blind, randomized, placebo-controlled trials","volume":"12","author":"A V\u00f6lp","year":"2022","journal-title":"Sci Rep"},{"key":"ref41","first-page":"489","article-title":"Wirksamkeit und Vertr\u00e4glichkeit Efeuhaltiger Hustenmittel","volume":"9","author":"W L\u00e4ssig","year":"1996","journal-title":"TW P\u00e4diatr"},{"key":"ref42","first-page":"28","article-title":"Wirksamkeit und Vertr\u00e4glichkeit von Efeuextrakt bei Patienten mit Atemwegserkrankungen","volume":"14","author":"M Hecker","year":"1999","journal-title":"Nat Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000057269","article-title":"Behandlung Chronischer Bronchitis mit einem Spezialextrakt aus Efeubl\u00e4ttern \u2013 Multizentrische Anwendungsbeobachtung mit 1350 Patienten","volume":"9","author":"M Hecker","year":"2002","journal-title":"Complement Med Res"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.phymed.2006.05.003","article-title":"Tolerance, safety and efficacy of Hedera Helix extract in inflammatory bronchial diseases under clinical practice conditions: A prospective, open, multicentre postmarketing study in 9657 patients","volume":"16","author":"S Fazio","year":"2009","journal-title":"Phytomedicine"},{"key":"ref45","first-page":"276","article-title":"Treatment of acute respiratory infections in Slovenian children with ivy leaf extract syrup","volume":"80","author":"A Beden","year":"2011","journal-title":"Slov Med J"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.phymed.2010.11.009","article-title":"Observational study on the tolerability and safety of film-coated tablets containing ivy extract (prospan cough tablets) in the treatment of colds accompanied by coughing","volume":"18","author":"M Stauss-Grabo","year":"2011","journal-title":"Phytomedicine"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1910656","DOI":"10.1155\/2020\/1910656","article-title":"Assessment of the efficacy and safety of ivy leaf (Hedera Helix) cough syrup compared with acetylcysteine in adults and children with acute bronchitis","volume":"2020","author":"E Kruttschnitt","year":"2020","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref48","first-page":"632","article-title":"The treatment of chronic-obstructive bronchitis in children","volume":"14","author":"A Gulyas","year":"1992","journal-title":"Sozialp\u00e4diatrie"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/00325481.2022.2015220","article-title":"Association between ivy leaves dry extract EA 575 prescriptions and antibiotic use, sick leave duration, and repeated infections in adult patients","volume":"134","author":"K Kostev","year":"2022","journal-title":"Postgrad Med"},{"key":"ref50","first-page":"179","article-title":"Vertr\u00e4glichkeit von Efeubl\u00e4ttertrockenextrakt im Kindesalter","volume":"25","author":"K Kraft","year":"2004","journal-title":"Z Phytother"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"781","DOI":"10.15446\/rcciquifa.v52n2.106481","article-title":"Clinical evolution of acute bronchitis in colombian children between 2 and 14 years treated with Hedera Helix EA575 syrup","volume":"52","author":"D Madero-Or\u00f3stegui","year":"2024","journal-title":"Rev Colomb Cienc Qu\u00edm-Farm"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1017\/S1463423611000193","article-title":"The natural history of acute upper respiratory tract infections in children","volume":"12","author":"A Mitra","year":"2011","journal-title":"Prim Health Care Res Dev"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0140-6736(03)12162-9","article-title":"The common cold","volume":"361","author":"T Heikkinen","year":"2003","journal-title":"The Lancet"},{"key":"ref54","first-page":"PA4388","article-title":"Responder rates in patients with acute cough treated with ivy leaves dry extract clearly exceed placebo response","volume":"62","author":"R M\u00f6sges","year":"2023","journal-title":"Eur Respir J"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/ppul.20161","article-title":"Do NHLBI lung function criteria apply to children? A cross\u2010sectional evaluation of childhood asthma at national Jewish medical and research center, 1999\u20132002","volume":"39","author":"K Paull","year":"2005","journal-title":"Pediatr Pulmonol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1164\/rccm.200308-1178OC","article-title":"Classifying asthma severity in children: Mismatch between symptoms, medication use, and lung function","volume":"170","author":"L B Bacharier","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jpeds.2007.05.004","article-title":"Value of the bronchodilator response in assessing controller na\u00efve asthmatic children","volume":"151","author":"S P Galant","year":"2007","journal-title":"J Pediatr"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jaci.2010.05.016","article-title":"Forced expiratory flow between 25\u200a% and 75\u200a% of vital capacity and FEV1\/forced vital capacity ratio in relation to clinical and physiological parameters in asthmatic children with normal FEV1 values","volume":"126","author":"M R Simon","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3109\/02770903.2012.690481","article-title":"The utility of forced expiratory flow between 25\u200a% and 75\u200a% of vital capacity in predicting childhood asthma morbidity and severity","volume":"49","author":"D R Rao","year":"2012","journal-title":"J Asthma"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1800904","DOI":"10.1183\/13993003.00904-2018","article-title":"Immediate bronchodilator response in FEV1 as a diagnostic criterion for adult asthma","volume":"53","author":"L E Tuomisto","year":"2019","journal-title":"Eur Respir J"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41598-025-85341-3","article-title":"Validation and accuracy of the Hyfe cough monitoring system: A multicenter clinical study","volume":"15","author":"C Chaccour","year":"2025","journal-title":"Sci Rep"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s41669-020-00221-y","article-title":"Real-world evidence: Bridging gaps in evidence to guide payer decisions","volume":"5","author":"M H Roberts","year":"2021","journal-title":"PharmacoEconomics Open"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1111\/all.15506","article-title":"Real\u2010world evidence for the long\u2010term effect of allergen immunotherapy: Current status on database\u2010derived european studies","volume":"77","author":"C Vogelberg","year":"2022","journal-title":"Allergy"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.3346\/jkms.2018.33.e213","article-title":"Real-world evidence versus randomized controlled trial: Clinical research based on electronic medical records","volume":"33","author":"H S Kim","year":"2018","journal-title":"J Korean Med Sci"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00228-021-03090-4","article-title":"Ivy leaf (Hedera Helix) for acute upper respiratory tract infections: An updated systematic review","volume":"77","author":"E Sierocinski","year":"2021","journal-title":"Eur J Clin Pharmacol"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s00134-018-5333-3","article-title":"Financial conflicts of interest in clinical research","volume":"44","author":"J Savovi\u0107","year":"2018","journal-title":"Intensive Care Med"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"1423250","DOI":"10.3389\/fped.2025.1423250","article-title":"Phytotherapy for acute respiratory tract infections in children: A systematically conducted, comprehensive review","volume":"13","author":"W Kamin","year":"2025","journal-title":"Front Pediatr"}],"container-title":["Planta Medica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2745-1130.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:30:39Z","timestamp":1783636239000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2745-1130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":64,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2026,7,9]]},"published-print":{"date-parts":[[2026,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2745-1130","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0032-0943","1439-0221"],"issn-type":[{"value":"0032-0943","type":"print"},{"value":"1439-0221","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1,23]]},"published":{"date-parts":[[2026,1,23]]}}}