Table 2.

Most common drugs’ dosing adjustment in children affected by obesity

Drug	TBW (Total Body Weight)	Use In Children Affected By Obesity
ANTIBIOTICS
Amoxicillin/clavulanic acid (combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor)	25–70 mg/Kg/die	The practice of capping the dose at the usual adult maximum did not seem to differ whether prescribing for children with obesity or for normal-weight children [17]. Use TBW dosing, possibly evaluating the posology based on the severity and site of infection [18]
Azithromycin (macrolide)	10 mg/kg/day	Underdosing the TBW: risk of overdose due to difficult elimination [19].
Cefazolin (first generation cephalosporine)	25-100 mg/kg/day	No dose adjustment for obesity [2, 5]
Ceftazidime (cephalosporine)	40 mg/kg IV q6h	The administration maximized the model-based probability of target attainment PTA in children and adolescents with obesity and GFR ≥ 80 mL/min/1.73 m2 [20]
Clindamycin (lincosamide)	20-40 mg/kg/day in three or four equal doses.	Recommended weight-based dosing in children with obesity [21, 22].
Ceftriaxone (third-generation cephalosporin)	50-100 mg/kg/day	TBW dosing has proven safe and effective in childhood obesity [23].
Linezolid (oxazolidinones)	10 mg/kg day, max 600 m	Weight-based dosing in children remains unclear. Data from adult patients suggest risks of linezolid underdosing in empirical antibiotic therapy of most resistant bacteria [19].
Meropenem (carbapenem)	20 mg/kg IV every 8 hours	Dosage adjustments based solely on body weight are unnecessary [24, 25, 26].
Trimethoprim/sulfamethoxazole (cotrimoxazole)	8 mg/kg/day trimethoprim	Patients with overweight/obesity may have decreased weight-normalized clearance and volume of distribution of the drug, so that should require higher absolute doses under recommended pediatric weight-based dosing regimens [2, 21, 24]
Vancomycin (glycopeptide)	20-40 mg/kg/day	No dose adjustment for obesity [20].
ANALGESICS AND ANESTHETICS
Acetaminophen/Paracetamol	10–15 mg/kg/day every 4-6 h <12y	No significant differences in circulating acetaminophen concentrations after a 5-mg/kg (up to 325 mg) single oral dose administration in children with NAFLD In adults there are higher concentrations of hepatotoxic CYP2E1-mediated acetaminophen metabolites. Adults with obesity may not tolerate high doses due the overproduction of hepatotoxic acetaminophen metabolites [2].
Dexmedetomidine (selective a2-agonist)	1 μg/kg	No differences in the dosage required for sedation in children suffering from obesity and those with normal weight [27]. Rolle et al. have found in their study that lean body mass (LBM) is an appropriate dosing scalar for size in adult patients with obesity [18].
Fentanyl (opiate agonist)	1–2 μg/kg/dose IM	Lipophilic. Adjusted Body Weight (cofactor of 0.25) has been recommended [28]. Mortensen et al. recommended TBW for induction and lean body weight (LBW) for maintenance of anesthesia [28].
Midazolam (benzodiazepine)	0.1–0.3 mg/kg, max 5 mg IV,IM	Potential need for higher initial drug dose administration for continuous infusion [29].
Morphine (opiate agonist)	0.1–0.15 mg/kg/dose every 4 h IM or 0.2–0.4 mg/kg/dose every 4 h OD	Dosing morphine is based on IBW because it is a hydrophilic opioid [28]. TBW not recommended.
Propofol (short-acting, lipophilic intravenous general anesthetic)	1–2 mg/kg pro dose	Diepstraten et al. proposed TBW-based dosing to achieve maintenance anesthesia [30].
OTHER DRUGS
Amlodipine (Calcium channel blocker)	0.1 mg/kg/day	TBW [31]
Angiotensin-Converting Enzyme Inhibitor (Ramipril)	0.05–0.15 mg/kg/day max 40 mg/day	TBW based dose: an empiric low starting dose can be used [2, 32]
Antipsychotics (e.g. haloperidol, thioridazine, risperidone, aripiprazole)		Few studies on their correct dosing and therapeutic drug monitoring. Start low, go slow and careful monitoring of patients’ metabolism Discontinuation attempts after long-term use can also be beneficial [33, 34, 35].
Atorvastatin (statins)	> 10y: 10-20 mg/day	Due to the correlation of statins with the genotypic variability of SLCO1B1, cases of statin overtreatment may occur [36].
Antineoplastic drugs	Depending on the drug and protocols	Doses of chemotherapy are commonly calculated based on a patient’s Body surface area, using TBW. Baillargeon et al. by studying children with leukemia found that 7% of those with obesity received less than the protocol-specified dose [37].
Inhaled corticosteroids (e.g. beclomethasone, budesonide, flunisolide, fluticasone)	Depending on the drug	Standard doses are insufficient for children with obesity [14, 38]
Liraglutide (analogous to glucagon-like peptide)	Same dose of adults (i.e. 3 mg, s.c.).	Children over 10 years of age with an indication of type 2 diabetes mellitus not correctly compensated with metformin indications also for the treatment of obesity in patients aged> 12 years weighing > 60 kg
Low-molecular weight Heparin	Depending on the drug and indication	Dose adjusting of enoxaparin dosing on initiation of therapy is necessary [39, 40]
Metformin (biguanide)	500 mg day, max 2 g/day	TBW dosing: higher drug doses than patients without obesity [2] Use of adult doses of metformin in older children and adolescents with obesity [41]
PPIs e.g., Pantoprazole	10–20 mg/day	Dosing PPIs in obesity can be the same as for normal-weight children [5, 42]
Steroids	Depending on indication	Need for standardization of drug dosing guidelines for children with obesity to avoid risk of harm [38].
Vitamin D	1000 and 2000 IU 25(OH)D /day	The highest percentages of patients affected by obesity with values ≥20 ng/ mL were seen only among the 2000-IU group, implying therefore the superiority in effectiveness of this dose in comparison to the lower ones [43]

IBW = [50th percentile Weight (age)*height(cm)], PPI Proton Pump Inhibitors, TBW Total Body Weight, LBM Lean Body Mass, NAFLD Non Alcoholic Fatty Liver Disease