Drug-DrugInteractionExtractionfromStructuredDrugLabels

Dina Demner-Fushman1, Kin Wah Fung1, Phong Do2

1 Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine

2 Office of Health Informatics, U.S. Food and Drug Administration

MechanismsofDrug-DrugInteraction

• A druginteraction resultswhentheeffectsofadrugarealteredinsomewaybythepresenceofanotherdrug,byfood,orbyenvironmentalexposure.

• Theriskofdevelopinganadversedrugreaction(ADR)secondarytoadrug–druginteractionincreasessignificantlywiththenumberofmedicationsapatientisreceiving.

• Mechanismsof druginteractions:• Apharmacodynamic interactionresultswhenadruginterfereswithaseconddrugatits

targetsite,orchangesinsomewayitsanticipatedpharmacologicresponse.Theconsequenceofthisinteractionresultsinadditivity,synergy,orantagonismoftheintendedeffect.Anexampleofapharmacodynamic interactionisthesynergismthatresultsfromcombiningtwoormoreanti-infectives inthetreatmentofaresistantpathogen.

• Pharmacokineticinteractionsoccurwhenonedrugalterstheabsorption,distribution,metabolism,oreliminationofanotherdrug,therebychangingitsconcentrationinplasmaand,consequently,atthetargetedsiteofaction.Clinicallysignificant druginteractions aremostoftenduetoalterationsinpharmacokinetics,secondarytomodulationofdrugmetabolism.

http://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/drug-interaction

RelevantSPLsections

BoxedWarning,Contraindications,DosageandAdministration,Drugand/orlaboratorytestinteraction,DrugInteractions,Precautions,WarningsandPrecautions,Warnings

Relatedwork

• AnattempttocombineallpublicallyavailablePDDIssources.• ThemergeddatasetconsistsoffourteendifferentsourcesofPDDIsinformation.

• Ayvaz S,HornJ,Hassanzadeh O,ZhuQ,StanJ,Tatonetti NP,Vilar S,Brochhausen M,Samwald M,Rastegar-Mojarad M,Dumontier M.Towardacompletedatasetofdrug–druginteractioninformationfrompubliclyavailablesources.Journalofbiomedicalinformatics.2015Jun30;55:206-17.

Annotation

• Entities• Drug• Drugclass• Substance• Span/Expression

• Interactionevents• Caution(Unspecified)• Increase/Decrease(Pharmacokinetic)• Specific(Pharmacodynamic)

I don't like this label

You still have to annotate it

Trainingset

Objective

• Identifysubstancesinteractingwiththelabeldrug• Identifyinteractiontype• Providejustification(sentencecontainingtheinteraction)• ProduceoutputforFDAreview:• SentencesfromthedesignatedSPLsections• Sectionname• Thetypeofinteraction– pharmacokinetic,pharmacodynamic orunspecified• Thelabeleddrugandgenericingredient(s)identifiedbytheSPLsetid• TheinteractingsubstanceencodedinUNII,orinNDF-RTNUIifitisadrugclass• TheconsequenceoftheinteractionencodedinSNOMEDCTifitisamedicalcondition,orinNationalCancerInstituteThesauruscodesifitisapharmacokineticeffect

Tasks

• Task1• ExtractInteractingDrugs/Substancesandthesentencesthatcontaininteractions.

• Task2• Identifytheinteractingdrugsandthespecificinteractiontypes:pharmacokinetic,pharmacodynamic orunspecified.

• Task3• NormalizetheinteractingsubstancetoUNII,andthedrugclassestoNDF-RTNUI.NormalizetheconsequenceoftheinteractiontoSNOMEDCTifitisamedicalcondition.NormalizepharmacokineticeffectstoNationalCancerInstituteThesauruscodes.

Data

• Training• NLM-DDICDcorpushttps://lhce-brat.nlm.nih.gov/NLMDDICorpus.htm

• Test• A:AutomaticallyannotatedsentencesreviewedandcorrectedbyFDA• B:Fullymanuallyannotatedsections(simplifiedannotations)