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American Academy of Pediatrics
Research Articles

Drug-Drug Interactions Among Hospitalized Children Receiving Chronic Antiepileptic Drug Therapy

Mollie Blazar Lebowitz, Karen L. Olson, Michele Burns, Marvin B. Harper and Florence Bourgeois
Hospital Pediatrics May 2016, 6 (5) 282-289; DOI: https://doi.org/10.1542/hpeds.2015-0249
Mollie Blazar Lebowitz
aDivision of Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts;bDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts; andcDepartment of Emergency Medicine, Newton Wellesley Hospital, Newton, Massachusetts
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Karen L. Olson
aDivision of Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts;bDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts; and
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Michele Burns
aDivision of Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts;bDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts; and
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Marvin B. Harper
aDivision of Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts;bDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts; and
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Florence Bourgeois
aDivision of Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts;bDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts; and
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  • FIGURE 1
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    FIGURE 1

    Types of acute medications associated with a potential drug-drug interaction. Note: there is overlap where some patients have interactions with multiple acute medication types.

  • FIGURE 2
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    FIGURE 2

    Year of CPOE implementation at study hospitals. Note: 4 hospitals had not initiated CPOE at the time of this study and are not included in the figure.

Tables

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    TABLE 1

    Characteristics of Hospitalized Patients Treated With an AED and Those With a pDDI

    pDDIs
    Treated With an AED (N = 434 794)Severe (n = 117 880)Nonsevere (n = 63 500)None (n = 253 414)
    Age, median (IQR), y8.3 (2.7, 14.3)6.5 (0.8, 14.1)11.0 (5.0, 15.5)8.2 (3.2, 18.3)
    Male gender, %53.452.256.553.4
    Number of hospital days, median (IQR)3 (2, 8)6 (3, 16)4 (2, 9)3 (1, 9)
    Number of AEDs per hospitalization, median (IQR)1 (1, 2)1 (1, 2)1 (1, 2)1 (1, 2)
    Number of non-AEDs per hospitalization, median (IQR)12 (6, 21)20 (12, 31)14 (8, 22)8 (4,16)
    ICU stay, %27.645.527.719.2
    Operating room procedure, %26.144.527.017.2
    Number of consulting services, median (IQR)2 (0, 2)2 (0, 2)2 (0, 2)2 (0, 2)
    Diagnosis count, median (IQR)6 (3, 11)8 (5, 14)7 (4, 11)5 (3, 9)
    Most common specialty of attending physician (top 3), %Pediatrics (22.2), Neurology (19.4), Hematology-Oncology (8.8)Pediatrics (21.8), Neurology (10.0), Surgery-Neurologic (9.5)Pediatrics (21.4), Neurology (14.1), Hematology-Oncology (12.0)Neurology (25.2), Pediatrics (22.6), Hematology-Oncology (9.7)
    Most common APR-DRG diagnosis (top 3), %Seizure (25.4), craniotomy for trauma (3.6), chemotherapy (3.1)Seizure (12.3), craniotomy for trauma (5.5), migraine/other headache (4.7)Seizure (19.1), bipolar (4.3), craniotomy for trauma (4.0)Seizure (33.0), chemotherapy (4.2), craniotomy for trauma (2.7)
    • A Kruskal-Wallis or χ2 analysis was performed to compare patients with severe, nonsevere, and no potential drug-drug interactions. All results were significant (P < .001). The most common specialties and diagnoses were not compared statistically. APR-DRG, all patient refined-diagnosis–related group; IQR, interquartile range.

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    TABLE 2

    AEDs and the Most Common Interacting Drugs as a Percentage of Hospitalizations With an AED

    Hospitalizations With pDDIs (N = 181 380)Hospitalizations With Severe pDDIs (N = 117 880)
    AEDAll Hospitalizations Associated With an AED (N = 434 794), Nn%aDrugs (Top 3)%an%bDrugs (Top 3)%b
    Phenobarbital96 99772 10139.8Lorazepam17.261 93252.5Lorazepam26.5
    Midazolam15.3Midazolam23.6
    Morphine14.8Morphine22.7
    Valproic acid70 76431 91817.6Lorazepam8.210 7139.1Ketorolac6.9
    Ketorolac4.5Trazodone1.3
    Risperidone3.1Meropenem0.8
    Phenytoin31 71225 78614.2Ranitidine6.211 73010.0Lidocaine6.0
    Fentanyl5.3Dopamine2.0
    Midazolam5.1Lidocaine and prilocaine1.8
    Gabapentin55 51523 45712.9Morphine10.986607.3Ketorolac6.8
    Ketorolac4.4Naproxen0.9
    Naproxen0.6——
    Clonazepam50 85715 6368.6Morphine5.715 47913.1Morphine8.8
    Oxycodone1.5Oxycodone2.4
    Hydromorphone1.3Hydromorphone1.9
    Carbamazepine22 06713 2247.3Fentanyl2.927442.3Ketorolac1.7
    Midazolam2.4Trazodone0.2
    Dexamethasone1.3Nifedipine0.2
    Topiramate58 53197985.4Ketorolac3.881616.9Ketorolac5.8
    Amitriptyline0.8Citalopram0.6
    Acetazolamide0.5Naproxen0.5
    Levetiracetam134 85975194.1Ketorolac4.175196.4Ketorolac6.4
    Oxcarbazepine54 65345782.5Ketorolac1.942213.6Ketorolac2.9
    Citalopram0.3Citalopram0.5
    Naproxen0.1Naproxen0.2
    Lamotrigine38 30036552.0Risperidone1.20———
    Sertraline0.5
    Escitalopram0.3
    Pregabalin581012990.7Ketorolac0.712991.1Ketorolac1.0
    Naproxen0.1Naproxen0.1
    Primidone13538970.5Lorazepam0.27410.6Lorazepam0.3
    Diazepam0.2Diazepam0.3
    Midazolam0.1Midazolam0.2
    Clobazam7212170.1Morphine0.01330.1Morphine0.1
    Omeprazole0.0Oxycodone0.0
    Oxycodone0.0Hydromorphone0.0
    Rufinamide35101920.1Ketorolac0.11920.2Ketorolac0.2
    Naproxen0.0Naproxen0.0
    Lacosamide29101520.1Ketorolac0.11520.1Ketorolac0.1
    Naproxen0.0Naproxen0.0
    Zonisamide21 4901150.1Metformin0.01150.1Metformin0.1
    Naproxen0.0Naproxen0.0
    Tiagabine656730.0Ketorolac0.0730.1Ketorolac0.1
    Naproxen0.0Naproxen0.0
    Vigabatrin68140.0Ketorolac0.040.0Ketorolac0.0
    Felbamate665330.0Warfarin0.00———
    Ethotoin7820.0Ketorolac0.020.0Ketorolac0.0
    Ethosuximide24870———————
    Methsuximide2190———————
    • ↵a Percentage of all hospitalizations with an AED associated with a pDDI.

    • ↵b Percentage of all hospitalizations with an AED associated with a severe pDDI.

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    TABLE 3

    Hospitalizations With an AED by Status of CPOE and Year of Admission

    pDDIs
    Number of HospitalizationsAnySevere
    Total434 794181 380 (41.7)117 880 (27.1)
    CPOE statusP = .48P = .91
     Pre-CPOE208 42789 023 (42.7)58 145 (27.9)
     Post-CPOE226 36792 357 (40.8)59 735 (26.4)
    Admit yearP < .001P < .001
     200546 81223 198 (49.6)14 748 (31.5)
     200650 36624 392 (48.4)15 716 (31.2)
     200755 52925 184 (45.4)16 437 (29.6)
     200858 84724 832 (42.2)16 365 (27.8)
     200963 05224 332 (38.6)15 830 (25.1)
     201056 66521 532 (38.0)13 884 (24.5)
     201169 07625 520 (36.9)16 707 (24.2)
     201234 45712 390 (36.0)8193 (23.8)
    • Data are presented as n (%) unless otherwise indicated. Post-CPOE begins in the year after the year of CPOE implementation. The effect of CPOE status and year of admission on the likelihood of a pDDI was evaluated with a random intercept logistic regression model, with observations clustered by hospital.

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Hospital Pediatrics: 6 (5)
Hospital Pediatrics
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1 May 2016
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Drug-Drug Interactions Among Hospitalized Children Receiving Chronic Antiepileptic Drug Therapy
Mollie Blazar Lebowitz, Karen L. Olson, Michele Burns, Marvin B. Harper, Florence Bourgeois
Hospital Pediatrics May 2016, 6 (5) 282-289; DOI: 10.1542/hpeds.2015-0249

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Drug-Drug Interactions Among Hospitalized Children Receiving Chronic Antiepileptic Drug Therapy
Mollie Blazar Lebowitz, Karen L. Olson, Michele Burns, Marvin B. Harper, Florence Bourgeois
Hospital Pediatrics May 2016, 6 (5) 282-289; DOI: 10.1542/hpeds.2015-0249
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