Table 2 Most common drugs’ dosing adjustment in children affected by obesity
From: Drug dosing in children with obesity: a narrative updated review
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 | |
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] |