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Medication Dosing in Pediatric Obesity Presents Complexities and Challenges

Drug Topics Journal, Drug Topics January 2023, Volume 167, Issue 1

Careful thought and adjustments are required to avoid exceeding the maximum recommended amount.

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 CDC and the American Academy of Pediatrics (AAP) 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 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.

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’s 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 certain treatments, such as chemotherapy.10-12 Patient-specific characteristics such as underlying organ function, illness severity, and extent of obesity must also be considered.

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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.

Medication Dosing Adjustments

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. To prevent potential errors, AAP 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:

• Younger than 18 years and less than 40 kg: utilize weight-based dosing

• Younger than 18 years 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

To see a listing of medications with special dosing considerations in pediatric obesity, visit https://bit.ly/3W9oIyZ.

Conclusion

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.

A version of this article originally appeared in Contemporary Pediatrics®, a sister publication of Drug Topics®.

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