Epidemiology of Polypharmacy and Potential Drug–Drug Interactions Among Pediatric Patients in ICUs of U.S. Children’s Hospitals*

Dai, Dingwei; Feinstein, James A.; Morrison, Wynne; Zuppa, Athena F.; Feudtner, Chris

doi:10.1097/pcc.0000000000000684

Cited by 87 publications

(140 citation statements)

References 40 publications

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“…Critically ill patients are often exposed to polypharmacy during an intensive care unit (ICU) admission . In addition, ICU‐admitted patients are at increased risk of DDIs because of the complexity of pharmacotherapy, disease severity, multiple comorbidities, and physiologic dysfunction arising from critical illness .…”

mentioning

confidence: 99%

Potential Drug–Drug Interactions Among Critically Ill Pediatric Patients in a Tertiary Pulmonary Center

Hassanzad

Arenas-López

Baniasadi

2017

The Journal of Clinical Pharma

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Patients in the pediatric intensive care unit (PICU) are at increased risk of potential drug-drug interactions (pDDIs) because of the complexity of pharmacotherapy. The current study aimed to assess the rate, pattern, risk factors, and management of pDDIs in the PICU of an academic pulmonary hospital. A prospective observational study was conducted for 6 months. Pharmacotherapy data of PICU-admitted patients were evaluated by a clinical pharmacologist. Interacting drugs, reliability, mechanism, potential outcome, and clinical management of pDDIs were identified using the Lexi-Interact database. Logistic regression was applied to analyze the risk factors that could be associated with the interactions. One hundred and twenty-three medication profiles were evaluated during the study period. Diseases of the respiratory system were the main diagnoses among intensive care unit (ICU)-admitted patients (56.1%). A total of 38.6% of the patients exposed to at least 1 major and/or contraindicated interaction during ICU admission. Most pDDIs occurred through metabolic (35.4%) and additive (34.8%) mechanisms. The existence of pDDIs was significantly associated with the number of prescribed medications. Exposure to pDDIs is frequent in critically ill pediatric patients and related to the number of medications. Daily and close cooperation between clinicians and clinical pharmacologists is recommended to prevent harmful outcomes of DDIs.

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mentioning

confidence: 99%

Potential Drug–Drug Interactions Among Critically Ill Pediatric Patients in a Tertiary Pulmonary Center

Hassanzad

Arenas-López

Baniasadi

2017

The Journal of Clinical Pharma

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“…4 It is estimated that 44.3%-87.9% of adult patients in the ICU and 75% of children in the NICU are exposed to a potential DDI. 5 Therefore, more predictive screening methodologies are required to reduce the incidences of DILI and DDIs.…”

Section: Introductionmentioning

confidence: 99%

An Automated Multiplexed Hepatotoxicity and CYP Induction Assay Using HepaRG Cells in 2D and 3D

Ott¹,

Ramachandran²,

Stehno‐Bittel

2017

SLAS Discovery

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Drug-induced liver injury (DILI) and drug-drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e., ATP depletion) and metabolism (i.e., cytochrome P450 1A [CYP1A] and cytochrome P450 3A4 [CYP3A4] enzyme activity) in two-dimensional (2D) and three-dimensional (3D) cell cultures. HepaRG cells were cultured in our proprietary micromold plates and produced spheroids. HepaRG cells, in 2D or 3D, expressed liver-specific proteins throughout the culture period, although 3D cultures consistently exhibited higher albumin secretion and CYP1A/CYP3A4 enzyme activity than 2D cultures. Once the spheroid hepatic quality was assessed, 2D and 3D HepaRGs were challenged to a panel of DILI-and CYP-inducing compounds for 7 days. The 3D HepaRG model had a 70% sensitivity to liver toxins at 7 days, while the 2D model had a 60% sensitivity. In both the 2D and 3D HepaRG models, 83% of compounds were predicted to be CYP inducers after 7 days of compound exposure. Combined, our results demonstrate that an automated multiplexed liver spheroid system is a promising cell-based method to evaluate DILI and DDI for early-stage drug discovery.

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“…Table lists commonly used medications in hospitalized pediatric patients and specifies whether the medicines have been specifically studied, prospectively or retrospectively, in obese individuals. The medication list is based on usage, which was collected in a drug interaction database accumulated from 42 U.S. pediatric intensive care units (PICUs) for patients ranging from infants, excluding neonates, to 17 years …”

Section: Nonobesity Drugs Used In Hospitalized Pediatric Patientsmentioning

confidence: 99%

“…The most‐used drugs from the PICU study are displayed as a list, ranked in order of prevalence of exposure, in . More than half the hospitalized pediatric patients had a prescription dispensed for acetaminophen, the single most frequently ordered drug, with the following exposure rates by age category: infants, 57.9%; children 1 through 9 years old, 58.0%; adolescents 10 through 17 years old, 50.7% . Despite the high prevalence of exposure to acetaminophen, it has been the subject of very few obesity studies in adults or in children with the obesity‐associated comorbidity of NAFLD .…”

Section: Nonobesity Drugs Used In Hospitalized Pediatric Patientsmentioning

confidence: 99%

Pediatric Obesity: Influence on Drug Dosing and Therapeutics

Ameer

Weintraub

2018

The Journal of Clinical Pharma

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Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of U.S. children and adolescents. Severe obesity (≥120% of the 95th percentile of body mass index (BMI) for age, or a BMI ≥ 35 kg/m2) is the fastest‐growing subgroup and now approaches 6% of all U.S. youth. Health consequences (eg, type 2 diabetes, coronary heart disease) are related in a dose‐dependent manner to severity of obesity. Because therapeutic interventions are less effective in severe obesity, prevention is a high priority. Treatment plans involving combinations of behavioral therapy, nutrition, and exercise achieve limited success. Only one drug, orlistat, is U.S. Food and Drug Administration approved for long‐term obesity management in adolescents 12 years and older. As part of comprehensive medication management, clinicians should consider the propensity for a given drug to aggravate weight gain and to consider alternatives that minimize weight impact. Medication management must take into account developmental changes as well as the pathophysiology of obesity and comorbidities. Despite expanding insight into obesity pathophysiology, there are gaps in its translation to therapeutic application. The historical construct of obesity as simply a fat‐storage disorder is fundamentally inaccurate. The approach to adjusting doses based solely on body size and extrapolating from therapeutic knowledge of adult obesity may be based on assumptions that are not fully substantiated. Classes of drugs commonly prescribed for comorbidities associated with obesity should be prioritized for clinical research evaluations aimed at optimizing dosing regimens in pediatric obesity.

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Epidemiology of Polypharmacy and Potential Drug–Drug Interactions Among Pediatric Patients in ICUs of U.S. Children’s Hospitals*

Cited by 87 publications

References 40 publications

Potential Drug–Drug Interactions Among Critically Ill Pediatric Patients in a Tertiary Pulmonary Center

Potential Drug–Drug Interactions Among Critically Ill Pediatric Patients in a Tertiary Pulmonary Center

An Automated Multiplexed Hepatotoxicity and CYP Induction Assay Using HepaRG Cells in 2D and 3D

Pediatric Obesity: Influence on Drug Dosing and Therapeutics

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