Pediatric obesity presents complexities in medication dosing

Contemporary PEDS JournalNovember/December 2022

Amy L. Kiskaddon, PharmD, MBA, BCPPS, discusses how medication doses need to be adjusted for pediatric patients with obesity.

Obesity in children and adolescents is a growing global public health concern. Recent data indicate that upward of 18.5% of children and adolescents in the United States have obesity.1,2 The Centers for Disease Control and Prevention and the American Academy of Pediatrics define obesity in individuals aged 2 to 20 years as a body mass index (BMI) equal to or above the 95th percentile of the percentile range on a specific BMI-for-age growth chart.3

Given pathophysiological changes associated with a higher body proportion of fat in obesity, drug pharmacokinetics may be altered, and therefore, adjustments to medication dosing may be required.4 Furthermore, there is a risk of drug doses exceeding the recommended maximum amount if total body weight (TBW) is used for weight-based dosing of certain drugs.5

However, because of the lack of pharmacokinetic studies of individual drugs in children and adolescents with obesity, there is limited guidance for determining whether drug dose adjustments are necessary. Evaluation of pharmacokinetic changes, drug properties, and patient factors are important considerations when determining optimal doses.

Pharmacokinetic changes in obesity

Given changes in body composition and physiology that occur in the setting of obesity, alterations in drug pharmacokinetics may result in therapeutic failure or toxicity (Table 1).5-7 Children and adolescents with obesity have a higher proportion of body fat and changes in volume of distribution (Vd), although the direction and magnitude are difficult to predict. Vd is affected by physiological changes that occur in obesity, such as body mass, extracellular water, tissue perfusion, and proportions of lean and fat tissue.5

Vd is typically larger for lipophilic medications because of distribution of the drugs into adipose tissues and is often altered for hydrophilic medications as well (ie, increased or decreased). Additionally, metabolism and clearance may be affected by obesity. It is thought that individuals with obesity may have changes in hepatic clearance and increased phase 1 and 2 reactions. Increased kidney size has been noted with higher TBW, leading to increased glomerular filtration rate.5-8 Collectively, these physiological and pharmacokinetic changes may require adjustments to the loading dose, dose interval, and time to reach steady state in certain medications.


Obesity effect

Examples of drugs





Increased Vd for highly lipophilic drugs

Altered Vd for water-soluble drugs

Benzodiazepines, opioids, propranolol

Aminoglycosidesa (ABW)


Reduced CYP3A4 activity, increased CYP CYP2E1 activity

Fentanyl, midazolam, carbamazepine


Increased with body weight, decreased depending on drug metabolism

Aminoglycosidesa, cimetidine, some benzodiazepines, steroids

Lipophilic drugs may accumulate in adipose tissue

Increased Vd and/or decreased clearance may prolong t½

Dependent on Vd and CL

ABW, adjusted body weight; CL, clearance; t½, half-life; Vd, volume of distribution.

aamikacin, gentamicin, tobramycin

Dosing in pediatric patients with obesity

Dosing regimens in pediatric patients are based on age, weight, and body surface area (BSA). Dosing based on weight and BSA is the most utilized method. However, in children and adolescents with obesity, this may lead to doses greater than the maximum dose for adults. Adjusted measures of weight have been developed to help accommodate these changes, including ideal body weight (IBW) and adjusted body weight (ABW) (Table 2).9,11 The selection of a size description for dosing is often considered when the patient TBW is greater than 120% of the IBW and prevents excess doses or accumulation of medications.11 Lean body weight may be used for maintenance dosing. BSA using the Mosteller equation for individuals aged 1 month to 14 years may also be used for certaintreatments, such as chemotherapy.10-12 Patient-specific characteristics such as underlying organ function, illness severity, and extent of obesity must also be considered. Additionally, medication characteristics including Vd, lipophilicity, hydrophilicity, and therapeutic range should be evaluated. Collectively, these factors are useful for determining appropriate loading and maintenance dosing. If a loading dose is required in pediatric patients with obesity, TBW is typically used for lipophilic drugs, ABW for partially lipophilic drugs, and IBW for hydrophilic drugs.

Weight description

Definition and calculation


Lean body mass+proportion of excess mass

IBW+prespecified cofactora× (TBW−IBW)

BSA (Mosteller)12

Square root [(height (cm)×weight (kg))/3600]


Lean body mass in children aged 2 to 20 years

[(50th percentile BMI-for-age)×(height in m)]2


Actual body weight

ABW, adjusted body weight; BMI, body mass index; BSA, body surface area; IBW, ideal body weight; TBW, total body weight.

aThe prespecific cofactor is medication specific.

Medication dosing adjustments in children and adolescents with obesity

Most data available to guide pediatric dosing recommendations are based on recommendations for adult patients with obesity.11 Given the limited published data to guide dosing in children and adolescents with obesity, attention should be given to dosing selected for individual medications (Table 3). To prevent potential errors, the American Academy of Pediatrics recommends that patients’ weights are appropriate for the weight-based dosing regimen and that adult doses are not exceeded. The Pediatric Pharmacy Association supports the following empiric dosing considerations for pediatric patients13:

  • Fewer than 18 years of age and less than 40 kg: utilize weight-based dosing
  • Fewer than 18 years of age and greater than or equal to 40 kg: utilize weight-based dosing with adult maximum doses or total daily doses for the specific indication
  • Therapeutic drug monitoring as indicated to ensure effective and safe therapy


Dosing considerations in pediatric obesity



TBW up to adult maximum dose, may consider IBW


TBW for loading doses, consider IBW for maintenance dosing


ABW, monitor for adverse effects


IBW for maintenance dosing and adult dosing, titrate to effect


IBW for maintenance dosing; titrate to effect, consider adult dosing


TBW up to adult maximum dose


IBW for maintenance dosing and adult dosing, titrate to effect


TBW up to adult maximum dose


Caution due to increased risk of adverse effects and accumulation of adipose tissue


IBW for maintenance dosing and adult dosing, titrate to effect


IBW for maintenance dosing and adult dosing, titrate to effect


Lower dose and titrate, monitor for adverse effects



TBW up to maximum adult dose


TBW up to maximum adult dose and monitor



Therapeutic drug monitoring to ensure within goal range


Therapeutic drug monitoring, may consider using ABW



IBW for maintenance dosing, use adult maximum dose


Use adult maximum dose


Monitor levels, consider extent of obesity and IBW for maintenance dosing


TBW, monitor levels

Valproic acid26

Use adult maximum dose



TBW up to adult maximum dose


TBW up to adult maximum dose


Therapeutic drug monitoring, consider extent of obesity and using IBW




Aminoglycosides (amikacin, gentamicin, tobramycin)26

ABW (cofactor of 0.4) and therapeutic drug monitoring


TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose




TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose, therapeutic drug monitoring










TBW, titrate to effect


TBW, titrate to effect


TBW, titrate to effect


TBW, titrate to effect


TBW up to adult maximum dose


TBW up to adult maximum dose







TBW up to adult maximum dose


TBW up to adult maximum dose


TBW up to adult maximum dose

H2-receptor antagonists34

TBW up to adult maximum dose

Immunoglobulin G33

IBW or adjusted body weight


TBW up to adult maximum dose

Proton pump inhibitors34

TBW up to adult maximum dose


TBW up to adult maximum dose, consider extent of obesity and use of ABW

ABW, adjusted body weight; H2, histamine2; IBW, ideal body weight; TBW, total body weight.


Given the continued rise of obesity in children and adolescents, thought should be given to dosing when selecting medications. Pathophysiologic changes associated with obesity can predict alterations in drug pharmacokinetics and pharmacodynamics, but consideration should be given to disease state and drug-specific properties. Therapeutic drug monitoring may also be of use where feasible to assess effectiveness and safety of dosing regimens. Future research should evaluate pediatric population pharmacokinetics/pharmacodynamics in children and adolescents with obesity.


  1. Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018;319(16):1723-1725. doi:10.1001/jama.2018.3060
  2. Ogden CL, Carroll MD, Lawman HG, et al. Trends in obesity prevalence among children and adolescents in the United States, 1988-1994 through 2013-2014. JAMA. 2016;315(21):2292-2299. doi:10.1001/jama.2016.6361
  3. Defining childhood weight status. Centers for Disease Control and Prevention. June 21, 2021. Accessed November 30, 2021.
  4. Nathan BM, Moran A. Metabolic complications of obesity in childhood and adolescence: more than just diabetes. Curr Opin Endocrinol Diabetes Obes. 2008;15(1):21-29. doi:10.1097/MED.0b013e3282f43d19
  5. Kendrick JG, Carr RR, Ensom MHH. Pediatric obesity: pharmacokinetics and implications for drug dosing. Clin Ther. 2015;37(9):1897-1923. doi:10.1016/j.clinthera.2015.05.495
  6. Sampson MR, Cohen-Wolkowiez M, Benjamin DK Jr, Capparelli EV, Watt KM. Pharmacokinetics of antimicrobials in obese children. GaBI J. 2013;2(2):76-81. doi:10.5639/gabij.2013.0202.025
  7. Xiong Y, Fukuda T, Knibbe CAJ, Vinks AA. Drug dosing in obese children: challenges and evidence-based strategies. Pediatr Clin North Am. 2017;64(6):1417-1438. doi:10.1016/j.pcl.2017.08.011
  8. Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71-87. doi:10.2165/11318100-000000000-00000
  9. Callaghan LC. Prescribing in paediatric obesity: methods to improve dosing safety in weight-based dose calculations. Arch Dis Child Educ Pract Ed.2018;103(5):274-277. doi:10.1136/archdischild-2016-311491
  10. Mulla H, Johnson TN. Dosing dilemmas in obese children. Arch Dis Child Educ Pract Ed. 2010;95(4):112-117. doi:10.1136/adc.2009.163055
  11. Ross EL, Heizer J, Mixon MA, et al. Development of recommendations for dosing of commonly prescribed medications in critically ill obese children. Am J Health Syst Pharm. 2015;72(7):542-556. doi:10.2146/ajhp140280
  12. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098. doi:10.1056/NEJM198710223171717
  13. Matson KL, Horton ER, Capino AC; Advocacy Committee for the Pediatric Pharmacy Advocacy Group. Medication dosage in overweight and obese children. J Pediatr Pharmacol Ther. 2017;22(1):81-83. doi:10.5863/1551-6776-22.1.81
  14. Zempsky WT, Bhagat PK, Siddiqui K. Practical challenges-use of paracetamol in children and youth who are overweight or obese: a narrative review. Paediatr Drugs. 2020;22(5):525-534. doi:10.1007/s40272-020-00417-z
  15. Kramer NM, Gazelka HM, Thompson VH, Batsis JA, Swetz KM. Challenges to safe and effective pain management in patients with super obesity: case report and literature review. J Pain Symptom Manage. 2018;55(3):1047-1052. doi:10.1016/j.jpainsymman.2017.11.005
  16. Kyler KE, Wagner J, Hosey-Cojocari C, Watt K, Shakhnovich V. Drug dose selection in pediatric obesity: available information for the most commonly prescribed drugs to children. Paediatr Drugs. 2019;21(5):357-369. doi:10.1007/s40272-019-00352-8
  17. Atyia SA, Smetana KS, Tong MC, Thompson MJ, Cape KM, May CC. Evaluation of dexmedetomidine dosing in obese critically ill patients. J Pharm Pract. 2021;8971900211021578. doi:10.1177/08971900211021578
  18. Fukuchi H, Nakashima M, Araki R, et al. Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. J Clin Pharm Ther. 2009;34(3):329-336. doi:10.1111/j.1365-2710.2008.00987.x
  19. Wells M, Goldstein L. The utility of pediatric age-based weight estimation formulas for emergency drug dose calculations in obese children. J Am Coll Emerg Physicians Open. 2020;1(5):947-954. doi:10.1002/emp2.12099
  20. Richard AA, Kim S, Moffett BS, Bomgaars L, Mahoney D Jr, Yee DL. Comparison of anti-Xa levels in obese and non-obese pediatric patients receiving treatment doses of enoxaparin. J Pediatr. 2013;162(2):293-296. doi:10.1016/j.jpeds.2012.07.047
  21. Lewis TV, Johnson PN, Nebbia AM, Dunlap M. Increased enoxaparin dosing is required for obese children. Pediatrics. 2011;127(3):e787-e790. doi:10.1542/peds.2010-0746
  22. Moffett BS, Teruya J, Petit C. Heparin dosing in obese pediatric patients in the cardiac catheterization laboratory. Ann Pharmacother. 2011;45(7-8):876-880. doi:10.1345/aph.1Q090
  23. Taylor BN, Bork SJD, Kim S, Moffett BS, Yee DL. Evaluation of weight-based dosing of unfractionated heparin in obese children. J Pediatr. 2013;163(1):150-153. doi:10.1016/j.jpeds.2012.12.095
  24. Caraco Y, Zylber-Katz E, Berry EM, Levy M. Carbamazepine pharmacokinetics in obese and lean subjects. Ann Pharmacother. 1995;29(9):843-847. doi:10.1177/106002809502900902
  25. Li ZR, Wang CY, Zhu X, Jiao Z. Population pharmacokinetics of levetiracetam: a systematic review. Clin Pharmacokinet. 2021;60(3):305-318. doi:10.1007/s40262-020-00963-2
  26. Lexicomp. Pediatric Lexi-Drugs Online, Hudson, Ohio: LexiComp Inc. Updated November 1, 2021. Accessed November 25, 2021.
  27. Donoso AF, Ulloa VD, Contreras DE, Arriagada SDS. Childhood obesity: pharmacokinetics considerations for drugs used in the intensive care unit. Arch Argent Pediatr. 2019;117(2):e121-e130. doi:10.5546/aap.2019.eng.e121
  28. Natale S, Bradley J, Nguyen WH, et al. Pediatric obesity: pharmacokinetic alterations and effects on antimicrobial dosing. Pharmacotherapy. 2017;37(3):361-378. doi:10.1002/phar.1899
  29. Zheng Y, Liu SP, Xu BP, et al. Population pharmacokinetics and dosing optimization of azithromycin in children with community-acquired pneumonia. Antimicrob Agents Chemother. 2018;62(9):e00686-18. doi:10.1128/AAC.00686-18
  30. Smith MJ, Gonzalez D, Goldman JL, et al. Pharmacokinetics of clindamycin in obese and nonobese children. Antimicrob Agents Chemother. 2017;61(4):e02014-16. doi:10.1128/AAC.02014-16
  31. Playfor S, Jenkins I, Boyles C, et al; United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockage Working Group. Consensus guidelines for sustained neuromuscular blockade in critically ill children. Paediatr Anaesth. 2007;17(9):881-887. doi:10.1111/j.1460-9592.2007.02313.x
  32. Amador N, Guizar JM, Malacara JM, Pérez-Luque E, Paniagua R. Sympathetic activity and response to ACE inhibitor (enalapril) in normotensive obese and non-obese subjects. Arch Med Res. 2004;35(1):54-58. doi:10.1016/j.arcmed.2003.08.010
  33. Siegel J. Immunoglobulins and obesity. Pharmacy Practice News. January 27, 2010.
  34. Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis. Crit Care. 2021;25(1):77. doi:10.1186/s13054-021-03495-8
Related Videos
Image credit: Kyle Dykes
Nicole Peña Sahdala, MD, internist, gastroenterologist specialist in bariatric endoscopy, ABIM certified | Image Credit: Provided
Related Content
© 2024 MJH Life Sciences

All rights reserved.