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TABLE 4

Potentially Major DDIs Among Children and Adolescents Concurrently Using Prescription Medications Overall and by Gender and Age Group in the United States (2009–2014)

Prevalence of DDIs, No. (%) [95% CI]
Overall, n = 9930–5 y6–12 y13–19 yAdverse Interaction Effect
Girls (n = 112)Boys (n = 159)Girls (n = 156)Boys (n = 244)Girls (n = 170)Boys (n = 152)
Any major DDI 78 (8.2) [6.0–11.1] 4 (3.0) [1.0–8.2]a 6 (3.0) [1.0–8.6]a 7 (3.0) [1.2–7.0]a 19 (5.7) [3.3–9.6] 30 (18.1) [11.0–28.4] 12 (6.6) [3.6–30.2]a**  
 Psychotherapeutic agents 48 (5.6) [3.6–8.6] 0 (0.0) 0 (0.0) 5 (2.2) [0.9–5.0]a 14 (4.4) [2.3–8.2]a 20 (12.5) [6.2–23.6]a 9 (5.4) [2.5–37.0]a 
 Antidepressants 33 (3.9) [2.5–6.1] 0 (0.0) 0 (0.0) 5 (2.2) [0.9–5.0]a 7 (2.2) [1.0–5.2]a 15 (9.1) [4.9–16.1] 6 (3.9) [1.5–46.5]a  
 SSRIs 21 (2.3) [1.4–3.9] 0 (0.0) 0 (0.0) 3 (1.5) [0.4–3.0]a 2 (0.7) [0.2–2.8]a 11 (4.9) [2.2–10.6]a 5 (3.7) [1.3–49.4]a 
  Citalopram–omeprazoleb 1 (0.4) [0.1–3.2]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.7) [0.2–11.5]a 0 (0.0) QT prolongation 
  Fluoxetine–trazodone 4 (0.4) [0.2–1.0]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.4) [0.1–3.0]a 2 (0.8) [0.2–3.2]a 1 (0.5) [0.1–96.4]a QTprolongation and/or serotonin syndrome 
  Escitalopram– amphetamines 1 (0.3) [0.0–2.3]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.6) [0.2–98.0]a Serotonin syndrome 
  Sertraline–amphetamines 3 (0.3) [0.1–0.9]a 0 (0.0) 0 (0.0) 1 (0.4) [0.1–1.0]a 0 (0.0) 1 (0.4) [0.1–2.7]a 1 (0.7) [0.1–100.0]a Serotonin syndrome 
  Escitalopram–hydroxyzineb 2 (0.2) [0.1–1.1]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) [0.0–2.0]a 1 (0.7) [0.1–4.7]a 0 (0.0) QT prolongation 
  Sertraline–trazodone 2 (0.1) [0.0–0.5]a 0 (0.0) 0 (0.0) 2 (0.8) [0.2–2.0]a 0 (0.0)* 0 (0.0) 0 (0.0) Serotonin syndrome 
  Fluoxetine–amphetamines 1 (0.1) [0.0–0.7]a 0 (0.0) 0 (0.0) 1 (0.7) [0.1–1.0]a 0 (0.0) 0 (0.0) 0 (0.0) Serotonin syndrome 
 Tricyclics 8 (1.4) [0.6–3.3]a 0 (0.0) 0 (0.0) 0 (0.0) 3 (1.0) [0.2–4.3]a 5 (4.5) [1.6–11.8]a 0 (0.0)*  
  Amitriptyline–albuterolb 1 (0.3) [0.0–2.5]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) [0.2–9.1]a 0 (0.0) Cardiovascular effects 
  Nortriptyline–ondansetronb 1 (0.3) [0.0–1.9]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.0) [0.1–6.9]a 0 (0.0) QT prolongation 
  Imipramine–quetiapine 1 (0.2) [0.0–1.1]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.7) [0.1–5.1]a 0 (0.0) 0 (0.0) QT prolongation 
 Atypical antipsychotics 21 (1.8) [1.1–3.1] 0 (0.0) 0 (0.0) 0 (0.0) 9 (3.3) [1.4–7.4]a8 (2.8) [1.3–5.9]a 4 (1.9) [0.7–49.2]a  
  Quetiapine–aripiprazole 3 (0.3) [0.1–1.3]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.8) [0.2–3.4]a 1 (0.4) [0.1–98.0]a QT prolongation 
  Risperidone–lithium 3 (0.3) [0.1–0.9]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) [0.0–2.3]a 0 (0.0) 2 (1.1) [0.3–69.8]a Extrapyramidal symptoms 
  Quetiapine–trazodone 3 (0.2) [0.1–0.8]a 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.5) [0.1–2.2]a 1 (0.5) [0.1–3.5]a 0 (0.0) QT prolongation 
  Quetiapine–risperidone 2 (0.2) [0.0–0.7]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.5) [0.1–3.2]a 1 (0.3) [0.0–2.1]a 0 (0.0) QT prolongation 
  Risperidone–hydroxyzineb 2 (0.1) [0.0–0.7]a 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.4) [0.1–3.1]a 0 (0.0) 0 (0.0) QT prolongation 
 CNS stimulants 14 (1.7) [0.8–3.5]a 0 (0.0) 0 (0.0) 4 (1.8) [0.6–4.0]a 3 (1.0) [0.3–3.2]a 4 (2.8) [0.7–10.8]a 3 (2.5) [0.6–67.9]a  
  Atomoxetine–albuterolb 2 (0.6) [0.1–3.2]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.5) [0.1–3.2]a 1 (1.9) [0.3–12.9]a 0 (0.0) Cardiovascular effects 
  Amphetamines–trazodone 4 (0.2) [0.1–0.6]a 0 (0.0) 0 (0.0) 2 (0.7) [0.2–2.0]a 2 (0.5) [0.1–2.2]a 0 (0.0) 0 (0.0) Serotonin syndrome 
  Methylphenidate–bupropion 3 (0.2) [0.0–0.5]a 0 (0.0) 0 (0.0) 1 (0.4) [0.1–1.0]a 0 (0.0) 1 (0.2) [0.0–1.5]a 1 (0.2) [0.0–99.2]a Seizures 
Analgesics 11 (1.4) [0.5–3.4]a 0 (0.0) 2 (0.6) [0.1–2.4]a 0 (0.0) 1 (0.2) [0.0–1.3]a 8 (4.9) [1.8–12.6]a 0 (0.0)*  
 Narcotics 7 (0.8) [0.3–1.9]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.2) [0.0–1.3]a 6 (3.0) [1.2–7.2]a 0 (0.0)*  
  Hydrocodoneb–oxycodoneb 2 (0.4) [0.1–1.7]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (1.5) [0.4–6.5]a 0 (0.0) CNS depression 
  Hydrocodoneb–cyclobenzaprineb 2 (0.2) [0.1–0.9]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.9) [0.2–3.5]a 0 (0.0) CNS depression 
 NSAIDs 4 (0.5) [0.1–2.5]a 0 (0.0) 2 (0.6) [0.1–2.4]a 0 (0.0) 0 (0.0) 2 (1.9) [0.3–9.6]a 0 (0.0)  
  Naproxenb–amitriptyline 1 (0.1) [0.0–0.6]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) [0.0–2.3]a 0 (0.0) Bleeding 
Antiemetic or antibiotics 14 (1.6) [0.9–2.8] 0 (0.0) 1 (1.1) [0.2–7.9]a 1 (0.4) [0.1–1.0]a 2 (0.5) [0.1–2.0]a 7 (4.0) [1.7–9.4]a 3 (1.2) [0.4–58.8]a  
 Promethazineb–azithromycinb 3 (0.3) [0.1–1.1]a 0 (0.0) 1 (1.1) [0.2–7.9]a 1 (0.4) [0.1–1.0]a 0 (0.0) 0 (0.0) 1 (0.3) [0.0–99.4]a QT prolongation 
 Ondansetronb–erythromycin 2 (0.2) [0.0–0.7]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.6) [0.1–2.6]a 0 (0.0) QT prolongation 
 Ondansetronb–clarithromycin 1 (0.1) [0.0–0.9]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.5) [0.1–3.2]a 0 (0.0) QT prolongation 
Prevalence of DDIs, No. (%) [95% CI]
Overall, n = 9930–5 y6–12 y13–19 yAdverse Interaction Effect
Girls (n = 112)Boys (n = 159)Girls (n = 156)Boys (n = 244)Girls (n = 170)Boys (n = 152)
Any major DDI 78 (8.2) [6.0–11.1] 4 (3.0) [1.0–8.2]a 6 (3.0) [1.0–8.6]a 7 (3.0) [1.2–7.0]a 19 (5.7) [3.3–9.6] 30 (18.1) [11.0–28.4] 12 (6.6) [3.6–30.2]a**  
 Psychotherapeutic agents 48 (5.6) [3.6–8.6] 0 (0.0) 0 (0.0) 5 (2.2) [0.9–5.0]a 14 (4.4) [2.3–8.2]a 20 (12.5) [6.2–23.6]a 9 (5.4) [2.5–37.0]a 
 Antidepressants 33 (3.9) [2.5–6.1] 0 (0.0) 0 (0.0) 5 (2.2) [0.9–5.0]a 7 (2.2) [1.0–5.2]a 15 (9.1) [4.9–16.1] 6 (3.9) [1.5–46.5]a  
 SSRIs 21 (2.3) [1.4–3.9] 0 (0.0) 0 (0.0) 3 (1.5) [0.4–3.0]a 2 (0.7) [0.2–2.8]a 11 (4.9) [2.2–10.6]a 5 (3.7) [1.3–49.4]a 
  Citalopram–omeprazoleb 1 (0.4) [0.1–3.2]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.7) [0.2–11.5]a 0 (0.0) QT prolongation 
  Fluoxetine–trazodone 4 (0.4) [0.2–1.0]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.4) [0.1–3.0]a 2 (0.8) [0.2–3.2]a 1 (0.5) [0.1–96.4]a QTprolongation and/or serotonin syndrome 
  Escitalopram– amphetamines 1 (0.3) [0.0–2.3]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.6) [0.2–98.0]a Serotonin syndrome 
  Sertraline–amphetamines 3 (0.3) [0.1–0.9]a 0 (0.0) 0 (0.0) 1 (0.4) [0.1–1.0]a 0 (0.0) 1 (0.4) [0.1–2.7]a 1 (0.7) [0.1–100.0]a Serotonin syndrome 
  Escitalopram–hydroxyzineb 2 (0.2) [0.1–1.1]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) [0.0–2.0]a 1 (0.7) [0.1–4.7]a 0 (0.0) QT prolongation 
  Sertraline–trazodone 2 (0.1) [0.0–0.5]a 0 (0.0) 0 (0.0) 2 (0.8) [0.2–2.0]a 0 (0.0)* 0 (0.0) 0 (0.0) Serotonin syndrome 
  Fluoxetine–amphetamines 1 (0.1) [0.0–0.7]a 0 (0.0) 0 (0.0) 1 (0.7) [0.1–1.0]a 0 (0.0) 0 (0.0) 0 (0.0) Serotonin syndrome 
 Tricyclics 8 (1.4) [0.6–3.3]a 0 (0.0) 0 (0.0) 0 (0.0) 3 (1.0) [0.2–4.3]a 5 (4.5) [1.6–11.8]a 0 (0.0)*  
  Amitriptyline–albuterolb 1 (0.3) [0.0–2.5]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) [0.2–9.1]a 0 (0.0) Cardiovascular effects 
  Nortriptyline–ondansetronb 1 (0.3) [0.0–1.9]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.0) [0.1–6.9]a 0 (0.0) QT prolongation 
  Imipramine–quetiapine 1 (0.2) [0.0–1.1]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.7) [0.1–5.1]a 0 (0.0) 0 (0.0) QT prolongation 
 Atypical antipsychotics 21 (1.8) [1.1–3.1] 0 (0.0) 0 (0.0) 0 (0.0) 9 (3.3) [1.4–7.4]a8 (2.8) [1.3–5.9]a 4 (1.9) [0.7–49.2]a  
  Quetiapine–aripiprazole 3 (0.3) [0.1–1.3]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.8) [0.2–3.4]a 1 (0.4) [0.1–98.0]a QT prolongation 
  Risperidone–lithium 3 (0.3) [0.1–0.9]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) [0.0–2.3]a 0 (0.0) 2 (1.1) [0.3–69.8]a Extrapyramidal symptoms 
  Quetiapine–trazodone 3 (0.2) [0.1–0.8]a 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.5) [0.1–2.2]a 1 (0.5) [0.1–3.5]a 0 (0.0) QT prolongation 
  Quetiapine–risperidone 2 (0.2) [0.0–0.7]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.5) [0.1–3.2]a 1 (0.3) [0.0–2.1]a 0 (0.0) QT prolongation 
  Risperidone–hydroxyzineb 2 (0.1) [0.0–0.7]a 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.4) [0.1–3.1]a 0 (0.0) 0 (0.0) QT prolongation 
 CNS stimulants 14 (1.7) [0.8–3.5]a 0 (0.0) 0 (0.0) 4 (1.8) [0.6–4.0]a 3 (1.0) [0.3–3.2]a 4 (2.8) [0.7–10.8]a 3 (2.5) [0.6–67.9]a  
  Atomoxetine–albuterolb 2 (0.6) [0.1–3.2]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.5) [0.1–3.2]a 1 (1.9) [0.3–12.9]a 0 (0.0) Cardiovascular effects 
  Amphetamines–trazodone 4 (0.2) [0.1–0.6]a 0 (0.0) 0 (0.0) 2 (0.7) [0.2–2.0]a 2 (0.5) [0.1–2.2]a 0 (0.0) 0 (0.0) Serotonin syndrome 
  Methylphenidate–bupropion 3 (0.2) [0.0–0.5]a 0 (0.0) 0 (0.0) 1 (0.4) [0.1–1.0]a 0 (0.0) 1 (0.2) [0.0–1.5]a 1 (0.2) [0.0–99.2]a Seizures 
Analgesics 11 (1.4) [0.5–3.4]a 0 (0.0) 2 (0.6) [0.1–2.4]a 0 (0.0) 1 (0.2) [0.0–1.3]a 8 (4.9) [1.8–12.6]a 0 (0.0)*  
 Narcotics 7 (0.8) [0.3–1.9]a 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.2) [0.0–1.3]a 6 (3.0) [1.2–7.2]a 0 (0.0)*  
  Hydrocodoneb–oxycodoneb 2 (0.4) [0.1–1.7]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (1.5) [0.4–6.5]a 0 (0.0) CNS depression 
  Hydrocodoneb–cyclobenzaprineb 2 (0.2) [0.1–0.9]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.9) [0.2–3.5]a 0 (0.0) CNS depression 
 NSAIDs 4 (0.5) [0.1–2.5]a 0 (0.0) 2 (0.6) [0.1–2.4]a 0 (0.0) 0 (0.0) 2 (1.9) [0.3–9.6]a 0 (0.0)  
  Naproxenb–amitriptyline 1 (0.1) [0.0–0.6]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) [0.0–2.3]a 0 (0.0) Bleeding 
Antiemetic or antibiotics 14 (1.6) [0.9–2.8] 0 (0.0) 1 (1.1) [0.2–7.9]a 1 (0.4) [0.1–1.0]a 2 (0.5) [0.1–2.0]a 7 (4.0) [1.7–9.4]a 3 (1.2) [0.4–58.8]a  
 Promethazineb–azithromycinb 3 (0.3) [0.1–1.1]a 0 (0.0) 1 (1.1) [0.2–7.9]a 1 (0.4) [0.1–1.0]a 0 (0.0) 0 (0.0) 1 (0.3) [0.0–99.4]a QT prolongation 
 Ondansetronb–erythromycin 2 (0.2) [0.0–0.7]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.6) [0.1–2.6]a 0 (0.0) QT prolongation 
 Ondansetronb–clarithromycin 1 (0.1) [0.0–0.9]a 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.5) [0.1–3.2]a 0 (0.0) QT prolongation 

Estimates are weighted to account for differential probabilities of selection and differential nonresponse. Micromedex was used to determine potential contraindicated and major DDIs among all medications used by children or adolescents who report using ≥2 medications during 2013–2014 (with Supplemental Table 6, we provide a list of these medications, and with Supplemental Table 7 , we provide a list of all DDIs found). Aripiprazole–metoclopramide is considered a contraindicated DDI; all other DDIs were considered potentially major DDIs. DDI, contraindicated or major DDI; SSRI, selective serotonin reuptake inhibitor.

a

Estimates are unreliable; relative SE >30%.

b

Acute medications (used ≤30 days).

**

P < .05; * P < .10 by using χ2 tests to determine differences between girls and boys.

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