How to choose an appropriate drug dosage form for the treatment of respiratory infections in children: Facts and tips
Abstract
The treatment of respiratory infections in children requires special attention, since the paediatric population has rather specific characteristics and consists of heterogenous subgroups. In this context, the choice of a suitable drug dosage form is of particular importance, depending on the active substance properties, along with the age and general condition of a paediatric patient. Тhe most commonly used pharmaceutical products for respiratory infections in children include oral, parenteral and inhalation dosage forms, although a large number of drugs are not available in a suitable dosage form and/or strength for paediatric age, leading to the frequent use of unauthorized drugs (i.e., unlicensed use). Other important issues that should be considered when choosing the appropriate paediatric dosage form and/or compounding procedure are related to the careful considerations of the pharmaceutical product composition (safety of excipients) and the choice of administration/dosing device in relation to a child’s age. This paper provides an overview of paediatric dosage forms used in the treatment of respiratory infections in children, their benefits and limitations. The review includes examples of various pharmaceutical products, along with the considerations regarding administration/dosing devices. Specific characteristics of paediatric populations affecting the decision on the choice of age-appropriate paediatric formulation are also addressed.
References
Ghimire P, Gachhadar R, Piya N, Shrestha K, Shrestha K. Prevalence and factors associated with acute respiratory infection among under-five children in selected tertiary hospitals of Kathmandu Valley. PLoS One. 2022;17(4): e0265933.
Tazinya AA, Halle-Ekane GE, Mbuagbaw LT, Abanda M, Atashili J, Obama MT. Risk factors for acute respiratory infections in children under five years attending the Bamenda Regional Hospital in Cameroon. BMC Pulm Med. 2018;18(1):7.
Bamel VV, Shahani SR, Mohanty NC. Study of drug utilization and antimicrobial prescription pattern of indoor paediatrics cases in tertiary care hospital. Int J Basic Clin Pharmacol. 2018;7:98-102.
European Medical Agency (EMA) [Internet]. Reflection paper: Formulations of choice for the paediatric population; 2006. [cited 2022 Apr 25]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf.
Ivanovska V, Rademaker CM, van Dijk L, Mantel-Teeuwisse AK. Pediatric drug formulations: a review of challenges and progress. Pediatrics. 2014;34(2):361-72.
British National Formulary for children 2021-2022. London: British Medical Association, Royal Pharmaceutical Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and Paediatric Pharmacists Group, 2021.
Guy’s and St. Thomas’, King’s College and University Lewisham Hospitals Paediatric Formulary. 9th ed. Tomlin S, Kirk E, editors. Guy’s & St Thomas’ NHS Foundation Trust, 2012.
Hoon D, Taylor MT, Kapadia P, Gerhard T, Strom BL, Horton DB. Trends in off-label drug use in ambulatory settings: 2006-2015. Pediatrics. 2019;144(4):e20190896.
Jong GW, Eland IA, Sturkenboom MC, van den Anker JN, Strickerf BH. Unlicensed and off-label prescription of respiratory drugs to children. Eur Respir J. 2004;23(2):310-3.
Badar V, Parulekar V, Garate P. A prescription pattern study of respiratory tract infections in paediatric indoor patients in a tertiary care teaching hospital - a prospective observational study. Asian J Pharm Clin Res. 2018;11(7):251-4.
Bandela A, Rathod S, Mullukuntla M, Guduru VK, Puchchakayala G. An assessment of antibiotic drugs utilization pattern in paediatric population. In J Phar Pract. 2019:12(4). doi: 10.5530/ijopp.12.4.53.
Alili-Idrizi E, Malaj L, Dauti M. Spectrum of infectious diseases and antibiotic usage in a paediatric outpatient department. Eur Sci J. 2013:.9(30):364-70.
World Health Organization [Internet]. WHO model prescribing information: drugs used in bacterial infections; 2001 [cited 2022 Apr 25]. Available from: https://apps.who.int/iris/handle/10665/42372.
World Health Organization [Internet] Development of paediatric medicines: points to consider in formulation. Annex 5, WHO Technical Report Series 970; 2012 [cited 2022 Apr 25]. Available from: https://cdn.who.int/media/docs/default-source/medicines/norms-and-standards/guidelines/trs970/annex5trs-970.pdf?sfvrsn=699cdb68_8&download=true.
Ivanovska V, Leufkens HG, Rademaker CM, Zisovska E, Pijnenburg MW, van Dijk L, et al. Are age-appropriate antibiotic formulations missing from the WHO list of essential medicines for children? A comparison study. Arch Dis Child. 2017:102(4):352-56.
World Health Organization [Internet]. WHO Model List of Essential Medicines for Children - 8th list; 2021 [cited 2022 Apr 25]. Available from: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.03.
World Health Organization [Internet]. WHO model formulary for children; 2010 [cited 2022 Apr 25]. Available from: https://apps.who.int/iris/handle/10665/44309.
Faizin C, Kusumawati W, Habib I. Evaluation of antibiotics prescription in the pediatric patient. JMMR. 2019:8(1):32-9.
Batchelor HK, Marriott JF. Formulations for children: problems and solutions. Br J Clin Pharmacol. 2015:79(3):405-18.
Medicines and Medical Devices Agency of Serbia [Internet]. [cited 2022 Apr 25]. Available from: https://www.alims.gov.rs/english/.
The electronic medicines compendium (emc) [Internet]. [cited 2022 Apr 20]. Available from: https://www.medicines.org.uk/emc/.
DailyMed [Internet]. [cited 2022 Apr 20]. Available from: https://dailymed.nlm.nih.gov/dailymed/.
Food and Drug Administration (FDA) [Internet]. Guidance for Industry Size of Beads in Drug Products Labeled for Sprinkle; 2012 [cited 2022 Apr 25]. Available from: https://www.fda.gov/files/drugs/published/Size-of-Beads-in-Drug-Products-Labeled-for-Sprinkle-Rev.1.pdf.
World Health Organization [Internet]. Revised WHO classification and treatment of childhood pneumonia at health facilities: EVIDENCE SUMMARIES; 2014 [cited 2022 Apr 25. Available from: https://apps.who.int/iris/bitstream/handle/10665/137319/9789241507813_eng.pdf.
Galande AD, Khurana NA, Mutalik S. Pediatric dosage forms—challenges and recent developments: A critical review. J App Pharm Sci. 2020;10(7):155-66.
Rashi G, Rampal M, Sujit P, Nikhl B. A review on medicated lollipops. Res J Pharmacognosy and Phytochem. 2021;13(1):33-8.
European Medicines Agency [Internet]. Committee for Medicinal Products for Human Use (CHMP). Guideline on pharmaceutical development of medicines for paediatric use; 2013 [cited 2022 Apr 20]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-pharmaceutical-development-medicines-paediatric-use_en.pdf.
Walsh J, Bickmann D, Breitkreutz J, Chariot-Goulet M, European Paediatric Formulation Initiative (EuPFI). Delivery devices for the administration of paediatric formulations: overview of current practice, challenges and recent developments. Int J Pharm. 2011:415(1-2):221-31.
Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126(3):532-7.
Bar-Shalom D, Rose K, editors. Pediatric formulations: a roadmap. New York: Springer; 2014. 273-8 p.
Borland ML, Bergesio R, Pascoe EM, Turner S, Woodger S. Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: a randomised double blind crossover study. Burns. 2005;31(7):831-7.
Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000;321(7253):83-6.
Ramvikas M, Arumugam M, Chakrabarti SR, Jaganathan KS. Nasal vaccine delivery. In: Skwarczynski M, Tóth I, editors. Micro and Nanotechnology in Vaccine Development. Amsterdam: William Andrew Publishing; 2017; p. 279-301.
Goldman RD. Intranasal drug delivery for children with acute illness. Curr Drug Ther. 2006;1(1):127-30.
Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res. 2013;3(1):42-62.
O’Brien F, Clapham D, Krysiak K, Batchelor H, Field P, Caivano G, et al. Making medicines baby size: The challenges in bridging the formulation gap in neonatal medicine. Int J Mol Sci. 2019;20(11):2688.
European Pharmacopoeia, 10th edition. Supplement 10.3. Strasbourg: Council of Europe, 2021.
Rouaz K, Chiclana-Rodríguez B, Nardi-Ricart A, Suñé-Pou M, Mercadé-Frutos D, Suñé-Negre JM, et al. Excipients in the paediatric population: A review. Pharmaceutics. 2021;13(3):387.
Annex to the European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’ (SANTE-2017-11668) EMA/CHMP [Internet]. 2019 [cited 2022 Apr 20]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/annex-european-commission-guideline-excipients-labelling-package-leaflet-medicinal-products-human_en.pdf.
Cutrera R, Baraldi E, Indinnimeo L, Miraglia Del Giudice M, Piacentini G, Scaglione F, et al. Management of acute respiratory diseases in the pediatric population: the role of oral corticosteroids. Ital J Pediatr. 2017;43(1):31.
Muchão FP, Filho LV. Advances in inhalation therapy in pediatrics. J Pediatr. (Rio J). 2010;86(5):367-76.
Wilmott RW. Hoods are effective for aerosol delivery in RSV bronchiolitis. J Pediatr. 2005;147(5):A3.
Heitman T, Day AJ, Bassani AS. Pediatric compounding pharmacy: taking on the responsibility of providing quality customized prescriptions. Children. 2019;6(5):66.
Jew RK, Soo-Hoo W, Erush SC, Amiri E, American Society of Health-System Pharmacists. Extemporaneous formulations: Extemporaneous formulations for pediatric, geriatric, and special needs patients. Bethesda, MD : American Society of Health-System Pharmacists, Inc.; 2016. xi-xiii p.
Barker C, Turner M, Sharland M. Prescribing medicines for children: From drug development to practical administration. London, UK: Pharmaceutical Press; 2019. 163-9 p.
Gudeman J, Jozwiakowski, M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs R&D. 2013;13(1):1-8.
Mullarkey, T. Pharmacy compounding of high-risk level products and patient safety. Am J Health Syst Pharm. 2009;66(17 Suppl 5):S4-13.
Scheepers HPA, Handlos VN, Walser S, Schutjens MDB, Neef, C. Impact of the Council of Europe Resolution on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. Eur J Hosp Pharm. 2017;24(4):218-23.
The United States Pharmacopoeia 42, The National Formulary 37, Rockville, MD: United States Pharmacopoeial Convention, 2019.
Minghetti P, Pantano D, Gennari CGM, Casiraghi A. Regulatory framework of pharmaceutical compounding and actual developments of legislation in Europe. Health Policy. 2014;117(3):328-33.
Resolution CM/Res(2016)1 on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. Committee of Ministers, Council of Europe, 2016.
PIC/S Guide to Good Practices for the Preparation of Medicinal Products in Healthcare Establishments, Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-Operation Scheme [Internet]. 2014 [cited 2022 Apr 20]. Available from: https://picscheme.org/docview/3443.
Allen LV. Gentamicin 40 mg/mL for Inhalation. US Pharm. 2015;40(7):57-8.
