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Not too little, not too much: problems of selecting oral antibiotic dose for children

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h5447 (Published 03 November 2015) Cite this as: BMJ 2015;351:h5447

Relatively Large Bottles Of Pediatrics Oral Suspensions: A Potential Factor For Inappropriate Use

Pediatric medications require special attention, and finding suitable formulations for children seems to be difficult. [1] Liquid formulations are most suitable for children, and are considered the most flexible, but they have some significant limitations.[2] The ideal formulation should fulfill a number of requirements to meet the needs of patients care caregivers[3], while it seems that appropriate pediatrics’ pharmaceutical preparations are often not available.[4] Antibiotics for pediatrics are usually prescribed and dispensed as oral suspensions. [5] A systematic review of the literature on medication errors in the Middle East countries stated that errors in the drug administration were a global concern and could have serious consequences. [6] Medication errors may occur in drug prescribing, distributing, or using; and have been reported frequently.[7, 8, 9 ]

Oral suspensions must be prepared with a fixed amount of water to make suspensions. The level at which water must be added, is usually indicated by the manufacturers, which is almost more than half the volume of the bottle. Some manufacturers, but not all, provide these preparations with a supplementary bottle of diluent. Studies reported inappropriate preparation of oral suspensions[10, 11] and problems in dosage of medicines for children. [ 6,12]

In recent years, a number of oral suspensions have been marketed, requiring the addition of a relatively small amount of water compared to the total size of the bottle. In other words, the final volume of the prepared suspensions is less than half of the total volume of the bottle. If they are mixed with additional water, the concentration of active ingredients will decrease and the result of treatment will be affected. Azithromycin and cefixime (many branded names) are examples of such pediatrics oral suspensions that are widely used antibacterials in Afghanistan. Reports indicate that some parents / caregivers add extra water (above the specified level) to these oral powders. This practice may result in further dilution of the active ingredient and, therefore, under-dosage and serious health risks. Oral suspensions packaged in relatively large bottles without solvent, are more likely to be inappropriately prepared. This problem occurs despite written instructions on the preparation of suspensions, and marking the level at which the water must be added. The issue of the illiteracy rate and the lack of knowledge of the language in which the bottle is labeled is overlooked here, as other studies in different countries with different illiteracy rates have confirmed the presence of errors in the preparation of the oral suspension by parent/caregivers.[7, 8, 9]

It is well known that empty space is required for proper mixing. If the dead space is not too large, although the addition of small amount of water can reduce the concentration of active substance, but more probably the concentration remains in the range of optimal doses, i.e. ±10 %. Adding as much as twice or more amount of water will reduce the concentration to a serious level that may lead to under- dosage, treatment failure; and in the case of antibiotics, to microbial resistance. The problems in the preparation of these suspensions endanger the health of patients, especially children who are the majority of recipients of these suspensions, and can contribute to microbial resistance. No studies have been found concerning the problems caused by the relatively large size of oral suspensions bottles.

In order to reduce the risks inappropriate use of oral suspensions, different educational approaches have already been proposed. [6, 13] Parents / caregivers education by prescribers, pharmacists and the media should be encouraged to provide appropriate information in this area. But regarding the problem due to relatively large bottles of pediatrics oral suspensions, without supplementary bottle of diluent; reviewing the packaging of these suspensions is recommended.

REFERENCES
1- Bielicki J A, Barker C I S, Saxena S, Wong I C K, Long P F, Sharland M et al. Not too little, not too much: problems of selecting oral antibiotic dose for children BMJ 2015; 351 :h5447
2- Zajicek A, Fossler MJ, Barrett JS, Worthington JH, et al. A report from the pediatric formulations task force: perspectives on the state of child-friendly oral dosage forms. AAPS J. 2013;15:1072–1081
3- Sam T, Ernest TB, Walsh J, et al. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection. Int J Pharm 2012;435(2):115
4- Knoppert DC (2009) Pediatric formulations: international issues and potential solutions. Paediatr. Drugs. 11(1): 55–56.
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6- Alsulami Z1, Conroy S, Choonara I. Medication errors in the Middle East countries: a systematic review of the literature.Medication errors in the Middle East countries: a systematic review of the literature. . Eur J Clin Pharmacol. 2013;69(4):995-1008. doi: 10.1007/s00228-012-1435-y
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10- Boztepe H, Ozdemir H, Karababa C, et al. Administration of oral medication by parents at home. J Clin Nurs. 2016;25:3345–3353.
11- Al-Ramahi, R. J., Zaid, A. A. N., & Anabousi, H. (2015). Problems associated with reconstitution, administration, and storage of antibiotic suspensions for pediatrics: a cross-sectional study in Nablus city, Palestine. BMC Research Notes, 8, 760. http://login.research4life.org/tacsgr0doi_org/10.1186/s13104-015-1746-z
12- McPhillips HA1, Stille CJ, Smith D, Hecht J, Pearson J, Stull J, Debellis K, Andrade S, Miller M, Kaushal R,Gurwitz J, Davis . Potential medication dosing errors in outpatient pediatrics. J Pediatr. 2005;147(6):761-7. Available from : http://login.research4life.org/tacsgr0www_ncbi_nlm_nih_gov/pubmed/16356427
13- Hu H, Wu FL, Hu FC, Yang HY, Lin SW, Shen LJ. Effectiveness of education programs about oral antibiotic suspensions in pediatric outpatient services. Pediatr Neonatol. 2013;54(1):34–42. doi: 10.1016/j.pedneo.2012.10.002

Competing interests: No competing interests

16 February 2019
Ahmad Farid Daanish
Professor in Pharmacology
Asif Atiq , Kabul University of Medical science, Farida Momand Kabul University of Medical science, Nazifa Faqiryar , Faculty of Pharmacy, Kabul University
Kabul University of Medical Science
Kabul, Afghanistan