TABLE 1

DDI Alert Refinements by the AAG During February 2015–February 2017

CategoryFrequency, %Override Rate, %Refinement DateAlert Refinement StrategyAAG Clinical Rationale for Alert Refinement
Potassium and potassium-sparing diuretics9.295.9December 14, 2015Alert only when previous potassium level was >4.8 mEq/L or when no potassium level has been obtained in 7 d.Serum potassium monitored routinely. Risk of unnoticed hyperkalemia present when patient is not monitored or has high serum potassium at initiation.
Potassium ACEI and/or ARB6.795.8December 14, 2015Alert only when previous potassium level was >4.8 mEq/L or when no potassium level has been obtained in 7 d.Serum potassium monitored routinely. Risk of unnoticed hyperkalemia present when patient is not monitored or has high serum potassium at initiation.
Posaconazole and H2 receptor blocker or PPI4.195.0December 14, 2015Alert only fires when posaconazole solution is ordered.Absorption affected by gastric pH only for oral solution dosage form of posaconazole.
Potassium and anticholinergics2.294.4December 14, 2015Alert only fires when anticholinergic is ordered with extended-release potassium.Risk of gastric damage due to delayed gastric emptying of anticholinergics only for extended-release dosage forms of potassium.
Fluoroquinolones and steroids1.295.9December 14, 2015SuppressThis extended a previous suppression of an individual DDI alert before the AAG formation to the class-class level.
Iohexol (intrathecal only) and lidocaine1.190.8December 14, 2015Suppress (suppression of all Iohexol intrathecal DDI alert interactions that occurred in July 2016)Iohexol is not administered via the intrathecal route in our patient population.
Methotrexate and P-glycoprotein inhibitors0.798.3December 14, 2015SuppressMethotrexate doses are monitored and adjusted via pharmacokinetic monitoring.
Diuretics and aminoglycosides0.792.9December 14, 2015SuppressBenefits of both medications outweigh risk of ototoxicity and nephrotoxicity. Patients are evaluated for both toxicity risks during evaluation before ordering.
NSAID and NSAID3.490.1March 9, 2016Alert only fires for 2 inpatient NSAID orders.Alert fired inappropriately for outpatient NSAID orders with inpatient ones. Alert only relevant when 2 active inpatient NSAID orders are present.
CNS depressant and CNS depressant0.589.0March 9, 2016SuppressPotential increased risk of CNS depression monitored closely in our patient population.
Methotrexate and PPI3.690.3August 26, 2016Alert only fires with high-dose methotrexate (doses >300 mg/m2).Elimination of methotrexate at high doses is impaired by PPIs.
5HT3 antagonist and serotonin modulator6.395.3September 12, 2016SuppressMajority of patient population receives serotonin antagonist. Low risk of serotonin syndrome that will be detected from inpatient and frequent outpatient clinic monitoring.
Midazolam and CYP3A4 inhibitor1.694.4September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Fentanyl and CYP3A4 inhibitor0.497.8September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Methadone and CYP3A4 inhibitor0.394.3September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Oxycodone and CYP3A4 inhibitor0.392.5September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Citalopram and CYP3A4 inhibitor0.198.6September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Salmeterol and CYP3A4 inhibitor0.197.3September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Escitalopram and CYP3A4 inhibitor0.195.4September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Itraconazole and CYP3A4 inhibitor0.195.9September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Oxycodone and CYP3A4 inhibitor0.191.4September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Fluticasone and CYP3A4 inhibitor0.194.8September 12, 2016Suppress on the basis of analysis of all CYP3A4 substrates and inhibitor interactions.CYP3A4 inhibition clinically insignificant for this medication for our patient population.
Olanzapine and benzodiazepines1.596November 21, 2016SuppressDDI occurs only with intramuscular formulations of both drugs. Olanzapine is not orderable via intramuscular route at our institution.
Deferasirox and NSAIDs1.397November 21, 2016Suppress for all NSAIDs (previously on suppressed for ibuprofen).This extended a previous suppression of an individual DDI alert before the AAG formation to the class-class level.
Tacrolimus and spironolactone197November 21, 2016Alert only when previous potassium level was >4.8 mEq/L or when no potassium level has been obtained in 7 d.Serum potassium monitored routinely. Risk of unnoticed hyperkalemia present when patient is not monitored or has high serum potassium at initiation.
  • None of the refinements above were detailed as DDIs that should always be active in pediatric EHRs.20 ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CNS, central nervous system; CYP3A4, cytochrome P450 3A4; PPI, proton pump inhibitor.