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Please use the "interaction categories" below to suggest examples of potential drug-drug interactions for the task force to use as it develops the minimum information model. You have the opportunity to add other categories toward the bottom of the spreadsheet
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The boxes that are highlighted in yellow (like this box) already have decision trees created for them by the IDIA group
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The boxes that are highlighted in light yellow (like this box) are other comments
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Provide an example of a potential drug-drug interaction that:Drug or Drug Class 1Drug or Drug Class 2Explanation / JustificationAdditional Comments
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can (and should) be contextualized for specific patients or clinical circumstancesTamoxifenParoxetinePatients with extensive 2D6 status on paroxetine will derive no benefit from tamoxifenInclusion agreed upon 4/28/16
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KCLK-sparing DiureticsCombination has known risk factorsInclusion agreed upon 4/28/16
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applies at the class levelMAOI Stimulants (indirect acting sympathomimetics)Inclusion agreed upon 4/28/16
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NSAIDsDiureticsInclusion agreed upon 4/28/16
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does not apply at the class levelMacrolidesStatinsazithromycin probably has little or no effect on 3A4, not all statins are 3A4 substratesInclusion agreed upon 4/28/16
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Tyrosine Kinase InhibitorsProton Pump Inhibitorsnot all Kinase inhibs have pH dependent absorption.
Imatinib, nilotinib, dasatinib, bosutinib, and ponatinib are BCR‐ABL tyrosine kinase inhibitors. Imatinib and ponatinib do not have a significant interaction due to pH dependent absorption with proton pump inhibitors, whereas nilotinib, dasatinib, and bosutinib do (Lexi‐comp and Micromedex).		Inclusion agreed upon 4/28/16
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the mechanism is known and is pharmacokinetic
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Warfarin2C9 inhibitors (ie. bactrim)Warfarin + 2C9 inhibs ie bactrimInclusion agreed upon 4/28/16
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digoxincyclosporinp-glycoproteinInclusion agreed upon 4/28/16
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the mechanism is known and is pharmacodynamicEpinephrineBeta-Blockersdifferentiates between selective and non-selective beta blockers; hypertensive crisisInclusion agreed upon 4/28/16
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NSAIDsACEI/ARBreduce antihypertensive response, reduced blood flow in kidneys, increased risk of toxicity, might be generally a weak interaction but special populations (elderly, kidney failure) pose a greater riskInclusion agreed upon 4/28/16
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the mechanism is not knownWarfarinIfosfamide/Etoposidecancer of the blood drugs - INR changes no mention of mechanismAgreement on 4/29 to elicit feedback from the group through a qualtrics survey
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Are etoposide and ifosfamide intended to be grouped together? There is a warfarin+etoposide interaction and and a warfarin+ifosfamide interaction (Micromedex), but case reports do not mention concomitant use of
etoposide and ifosfamide. We could pick etoposide or ifosfamide, or we could use those as 2 separate examples of when the interaction is unknown		Inclusion agreed upon 5/19/16
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WarfarinFibratesAnother one needed - will elicit suggestions through a qualtrics survey (4/29)
Suggested through 05/14 Qualtrics survey		References might provide a mechinism making this less of an unknown. Fibrates are not all the same. E.g., Gemfibrozil and 2C9 inhibitor. Fibratss should be narrowed down.
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PravastatinParoxetineIncreasing blood glucose
https://www.nigms.nih.gov/news/meetings/documents/russ_altman_article.pdf		Suggested through 05/14 Qualtrics surveyConcern that findings are perhaps spurious and not clinically meaningful because data mining result. But that could be ok because it might be a good example where including it highlights research to be done
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WarfarinAcetaminophenAcetaminophen with warfarin has some proposed mechanisms but it unknown per Micromedex and Lexicomp.Suggested through 05/14 Qualtrics survey
Can you remind me on the call why are we calling this type of interaction? If we don't know the mechanism, what will change in our approach to presenting this information to the clinician? or what will change in how we represent this type of interaction in the information model?		A couple of studies have looked at this bu unknown mechanismInclusion agreed upon 5/19/16
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the evidence supporting the interaction is strongEpinephrineBeta-BlockersI agree with epinephrine and beta-blockers and NSAIDs. Inclusion agreed upon 5/19/16
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simva, atorva, lovastatinClarithromycinCan we modify statins + clarithromycin to CYP3A4 statins + clarithromycin? The statins + clarithromycin is less strong in my opinion (after very brief review). I think it is strong for statins metabolized by CYP3A4 (simva, atorva, and lovastatin). I think the interaction which applies to all statins due to inhibition of transporter SLCO1B1 (OATP1B1) is not as strong.Inclusion agreed upon 5/19/16
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the evidence supporting the interaction is weakCitalopramAmiodaroneLittle evidence of harmI said no because I don't know the evidence behind these well enough to say Yes. A more appropriate response to would be I neither agree nor disagree.Stricken because there is some refuting evidence and there is little evidence of clinical effect. However, there may be a evidence of a pharmacokinetc effect
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WarfarinAntibiotics that don't inhibit CYP2C9
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the frequency of exposure data is availableWarfarinNSAIDspaper by Malone et al. - National sample
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SpironolactoneEnalaprilstudy published by Juurlink using Canadian data Suggested through 05/14 Qualtrics survey
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when you say frequency, do you mean the frequency in the population (like % of all Americans who will receive drugs A + B together in any given year), the proportion of all prescriptions for the object that overlap with the precipitant, or something else?
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Regarding frequency of adverse event and exposure data, to do a thorough review takes a substantial amount of time; perhaps we can use the examples we've agreed upon to find instances of the frequency categories.
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the frequency of exposure data is not availableMostMostYep, little data availablePerhaps, we don't need this as a category to call out since most have little data on frequency available.
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SimvastatinFluconazoleSuggested through 05/14 Qualtrics survey
These studies are rare
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WarfarinMetronidozaleSuggested through 05/14 Qualtrics survey
These studies are rare
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When you say that 'frequency of exposure data is not available', I assume you mean frequency of concomitant use of the object + precipitant, right?
When you say 'not available' do you mean not published, or not calculable from health care data, or something else?
Similarly, when you say frequency, do you mean the frequency in the population (like % of all Americans who will receive drugs A + B together in any given year), the proportion of all prescriptions for the object that overlap with the precipitant, or something else?
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the frequency of adverse event data is availableSpironolactonePotassium supplementsRisk of hospitalizationSuggested through 05/14 Qualtrics survey
After a brief search, frequency of adverse event/exposure data for potassium with triamterene was lacking, but there was some frequency data
on potassium with spironolactone
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Maybe we don't need "frequency of adverse event data is available" as a special category since this applies to most potential drug drug interactions.
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By frequency of the adverse event, do you mean the absolute risk or the risk attributable to the interaction?
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Similarly, when you say frequency, do you mean the frequency in the population (like % of all Americans who will receive drugs A + B together in any given year), the proportion of all prescriptions for the object that overlap with the precipitant, or something else?
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Again, regarding frequency of adverse event and exposure data, to do a thorough review takes a substantial amount of time; perhaps we can use the examples we've agreed upon to find instances of the frequency categories.
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the frequency of adverse event data is not availableMostMostallMaybe we don't need to call this out as a special category.
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SimvastatinFluconazoleSuggested through 05/14 Qualtrics survey
There might be a study but I am not aware of it
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WarfarinMetronidozaleSuggested through 05/14 Qualtrics survey
There might be a study but I am not aware of it
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I think that we want this category so we can show show the need to fill in gaps in this knowledge for DDIs such as 'warfarin - SSRIs' and 'metocloproomide and antipsych, rivastigmine'
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When you say 'not available' do you mean not published, or not calculable from health care data, or something else?
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the recommended action is “monitor” or “take note”MostMostMonitor will avoid patient risk in most casesI think this is good to include as a special category even though it applies to many potential DDIs. If the informational model highlights this situation, the warning/cds provided by an EHR could be different than if the recommended action is avoid/modify therapy.
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Warfarin 2C9 inhibitorsmonitor the INR and adjust warfarin dosing as neededI’m wondering if we can use the examples we’ve already agreed upon as potenĕal examples of the above categories
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Warfarinetoposidemonitor INR
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SulfonylureasACE inhibitorsSuggested through 05/14 Qualtrics survey
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Beta-adrenergic blockersSerotonin reuptake inhibitorsSuggested through 05/14 Qualtrics survey
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KCLK-sparing DiureticsSuggested through 05/14 Qualtrics survey
Very common interaction but not much is done.
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the recommended action is “avoid”ColchicineClarithromycinPackage insert for colchicine (Colcrys) provides a dosage adjustment during concomitant strong cyp3a4 inhibitor use. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ecaa34e-1bed-49a5-b97c-a8f8c0d885a7
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MAOIsIndirect SympathomimeticsI agree for MAOI + indirect sympathomimetcs.
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Other suggested actions: the recommended action is: monitor, switch one of the drugs, adj doses
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