Ambroxol for the treatment of children with acute and chronic respiratory diseases: an overview of efficacy and safety
Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine), an over-thecounter product, is a mucoactive agent and has been used widely to treat both acute and chronic respiratory diseases since 1978. This review aims to provide an overview of the clinical evidence available on the use of ambroxol in children with acute and chronic respiratory diseases. Data for this review were obtained from both published and unpublished clinical studies, and real-world evidence studies. Although conducted prior to the introduction of Good Clinical Practice (GCP), these studies, representing almost 1,300 pediatric patients, report strong clinical outcomes following the use of ambroxol in pediatric patients. Furthermore, efficacy findings were consistent irrespective of age, including for patients as young as 1 month old. Additionally, the majority of studies found ambroxol to be well tolerated in children. Taken together, the clinical evidence for ambroxol shows treatmenteffects that offer significant benefits to pediatric patients for its licensed use as a secretolytic therapy in acute and chronic bronchopulmonary disorders associated with abnormal mucus secretion and impaired mucus transport. The findings from this review indicate that ambroxol, for its intended over-the-counter indications, is both efficacious and well tolerated in children and that the favorable benefit/risk profile of ambroxol reported in adults extends to the pediatric population, starting from early infancy, with acute and chronic respiratory diseases.
Morice A, Kardos P. Comprehensive evidence-based review on European antitussives. BMJ Open Respir Res 2016;3:e000137. DOI: https://doi.org/10.1136/bmjresp-2016-000137
Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest 2006;S129:95-103. DOI: https://doi.org/10.1378/chest.129.1_suppl.95S
Thompson M, Cohen HD, Vodicka TA, Blair PS, Buckley DI, Henegan C, et al. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 2013;347:f7027. DOI: https://doi.org/10.1136/bmj.f7027
Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chest 2006;129:S260-83. DOI: https://doi.org/10.1378/chest.129.1_suppl.260S
Schroeder K, Fahey T. Should we advise parents to administer over the counter cough medicines for acute cough? Systematic review of randomised controlled trials. Arch Dis Child 2002;86:170-5. DOI: https://doi.org/10.1136/adc.86.3.170
Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev 2014:CD001831. DOI: https://doi.org/10.1002/14651858.CD001831.pub5
Balsamo R, Lanata L, Egan CG. Mucoactive drugs. Eur Respir Rev 2010;19:127-33. DOI: https://doi.org/10.1183/09059180.00003510
European Medicine Agencies. Revised assessment report: Ambroxol and bromhexine containing medicinal products 2015. Available from: https://www.ema.europa.eu/en/documents/referral/ambroxol-bromhexine-article-31-referral-prac-assessment-report_en.pdf
Zanasi A, Mazzolini M, Kantar A. A reappraisal of the mucoactive activity and clinical efficacy of bromhexine. Multidiscip Respir Med 2017;12:7. DOI: https://doi.org/10.1186/s40248-017-0088-1
Gupta PR. Ambroxol - Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India 2010;27:46-8. DOI: https://doi.org/10.4103/0970-2113.63603
Paleari D, Rossi GA, Nicolini G, Olivieri D. Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov 2011;6:1203-14. DOI: https://doi.org/10.1517/17460441.2011.629646
Zhang ZQ, Wu QQ, Huang XM, Lu H. Prevention of respiratory distress syndrome in preterm infants by antenatal ambroxol: a meta-analysis of randomized controlled trials. Am J Perinatol 2013;30:529-36. DOI: https://doi.org/10.1055/s-0032-1329684
Cazan D, Klimek L, Sperl A, Plomer M, Kolsch S. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert Opin Drug Saf 2018;17:1211-24. DOI: https://doi.org/10.1080/14740338.2018.1533954
Sanofi-Aventis. Ambroxol - Summary of Product Characteristics 2019. Available from: https://www.mucosolvan.de
Disse BG. The pharmacology of ambroxol -review and new results. Eur J Respir Dis Suppl 1987;153:255-62.
Fois G, Hobi N, Felder E, Ziegler A, Miklavc P, Walther P, et al. A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca(2)(+) release from acidic Ca(2)(+) stores. Cell Calcium 2015;58:628-37. DOI: https://doi.org/10.1016/j.ceca.2015.10.002
Glowania A MR, Böhm M, Knopf A, Klimek L. The surfactant system – a new approach for treating the upper respiratory tract mucosa. Atemwegs Lungenkrankh 2011;37:S1-5. DOI: https://doi.org/10.5414/ATX01743
K Morgenroth JB. Morphological features of the interaction between mucus and surfactant on the bronchial mucosa. Respiration 1985;47:225-31. DOI: https://doi.org/10.1159/000194774
Disse BG, Ziegler HW. Pharmacodynamic mechanism and therapeutic activity of ambroxol in animal experiments. Respiration 1987;51:S15-22. DOI: https://doi.org/10.1159/000195270
Hasegawa I, Niisato N, Iwasaki Y, Marunaka Y. Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia. Biochem Biophys Res Commun 2006;343:475-82. DOI: https://doi.org/10.1016/j.bbrc.2006.03.009
Muroi Y, Undem BJ. Targeting voltage gated sodium channels NaV1.7, Na V1.8, and Na V1.9 for treatment of pathological cough. Lung 2014;192:15-20. DOI: https://doi.org/10.1007/s00408-013-9533-x
Yang B, Yao DF, Ohuchi M, Ide M, Yano M, Okumura Y, et al. Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels. Eur Respir J 2002;19:952-8. DOI: https://doi.org/10.1183/09031936.02.00253302
Li F, Yu J, Yang H, Wan Z, Bai D. Effects of ambroxol on alginate of mature Pseudomonas aeruginosa biofilms. Curr Microbiol 2008;57:1-7. DOI: https://doi.org/10.1007/s00284-008-9142-8
Deretic V, Timmins GS. Enhancement of lung levels of antibiotics by ambroxol and bromhexine. Expert Opin Drug Metab Toxicol 2019;15:213-8. DOI: https://doi.org/10.1080/17425255.2019.1578748
Basabe-Burgos O, Zebialowicz J, Stichtenoth G, Curstedt T, Bergman P, Johansson J, et al. Natural derived surfactant preparation as a carrier of polymyxin E for treatment of Pseudomonas aeruginosa pneumonia in a near-term rabbit model. J Aerosol Med Pulm Drug Deliv 2019;32:110-8. DOI: https://doi.org/10.1089/jamp.2018.1468
Vijayananthan A, Nawawi O. The importance of good clinical practice guidelines and its role in clinical trials. Biomed Imaging Interv J 2008;4:e5. DOI: https://doi.org/10.2349/biij.4.1.e5
Principi N, Zavattini G, Daniotti S. Possibility of interaction among antibiotics and mucolytics in children. Int J Clin Pharmacol Res 1986;6:369-72.
Careddu P, Zavattini G. Mucosolvan® (Ambroxol) in paediatric use - Controlled clinical trial vs. acetylcysteine. Asthma Bronch Emphys 1984;4:23-26.
Berni M, Collina A, Zavattini G. [Ambroxol in bronchopulmonary pathology in children].[Article in Italian]. Clin Ter 1983;106:351-5.
Baldini G, Gucci M, Tarò D, Memmini C. [Controlled clinical study of a new ambroxol formulation in the treatment of infantile spastic bronchitis in children].[Article in Italian]. Min Ped 1989;41:91-5.
Boehringer Ingelheim International GmbH. Data on file (U86-0347). 1983.
Boehringer Ingelheim International GmbH. Data on file (U86-0348). 1983.
Weinmann HM. Ambroxol (Mucosolvan) in paediatrics. Clinical results with different forms of administration. Therapiewoche 1981;31:7940-7.
Boehringer Ingelheim International GmbH. Data on file (U75-0124). 1985.
Huizar Lara H, Ortega Guzman S, Quiroga Garza S. [Ambroxol, a new bronchosecretolytic in paediatric bronchopulmonary conditions].[Article in Spanish]. Invest Med Int 1985;11:83-90.
Boehringer Ingelheim International GmbH. Data on file (U84-0264). 1983.
Kardos P, Beeh KM, Sent U, Mueck T, Grater H, Michel MC. Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations. BMC Pharmacol Toxicol 2018;19:40. DOI: https://doi.org/10.1186/s40360-018-0229-y
Schulz M, Hammerlein A, Hinkel U, Weis G, Gillissen A. Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study. Int J Clin Pharmacol Ther 2006;44:409-21. DOI: https://doi.org/10.5414/CPP44409
Baranwal AK, Murthy AS, Singhi SC. High-dose oral ambroxol for early treatment of pulmonary acute respiratory distress syndrome: an exploratory, randomized, controlled pilot trial. J Trop Pediatr 2015;61:339-50. DOI: https://doi.org/10.1093/tropej/fmv033
Cataldi M, Sblendorio V, Leo A, Piazza O. Biofilm-dependent airway infections: a role for ambroxol? Pulm Pharmacol Ther 2014;28:98-108. DOI: https://doi.org/10.1016/j.pupt.2013.11.002
- Abstract views: 1879
- PDF: 3254
- HTML: 11
Copyright (c) 2020 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.