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ClinicalGuideforCommunityPharmaciststoEvaluateRisksandManageQTc ProlongationDuetoDrug-DrugInteractions
TracyHe1,PharmD Candidate,Certina Ho2,BScPhm,MISt,MEd,PhD1UniversityofWaterlooSchoolofPharmacy,2InstituteforSafeMedicationPracticesCanada
x
Results&KeyFindingsBackground
Objectives
Methods
Conclusions&FutureDirections References
Figure1.ClinicalguideforevaluationofgeneralQTc prolongingdrug-druginteractions.3,4
Figure2.ClinicalguideforevaluationofcitalopramQTc prolongingdrug-druginteractions.8
§ LongQTsyndrome(QTprolongation)isaconditionwheretheintervalbetweenthebeginningoftheQRScomplextotheendoftheTwaveislengthened,reflectingdelayedmyocardialrepolarization.1
§ “QTc”denotestheQTintervalcorrectedforapatient’sheartrate.2§ QTc prolongationcanprecipitatetotorsades depointes(TdP),alife-
threateningventriculartachyarrhythmiathatresultsinsuddendeath.1§ Itisduetogeneticsusceptibilityandmedications.1§ ClinicalsignificanceofQTc prolongationisunderestimatedand
overvalued.§ Currently,therearenovalidatedriskscalesthatassessQTc
prolongationriskforoutpatientorambulatorypatients.
1) ToidentifytherecommendationsposedbycliniciansinevaluatingQTcprolongationrisksassociatedwiththreecommonly-encountereddrugs(citalopram,domperidone,ciprofloxacin)thatmayresultinQTcprolongationalertsinthecommunitypharmacy;and,
2) Todevelopaclinicalalgorithmortherapeuticthoughtprocessforcommunitypharmaciststoeffectivelyevaluateandmanagethesedrug-druginteractions(DDIs).
Therecommendationswerecompiledthrough2methods.1)EnvironmentalScanofNationalRegulatoryBodiesandClinical
Guidelines
2)SystematicReviewofPrimaryLiterature
RegulatoryBodies• HealthCanada• UnitedStatesFoodandDrugAdministration(FDA)
ClinicalGuidelines• CanadianNetworkforMoodandAnxietyTreatmentsAmericanPsychiatricAssociation(CANMAT)
• AmericanAssociationofGastroenterology(AAG)
• CanadianJournalofUrology(CJU)
• CanadianThoracicSociety(CTS)
• EvaluationofQTc prolongingdrug-druginteractionsishighlyreliantontheclinicaljudgmentofthecommunitypharmacist,involvingananalysisofthepatient’sriskfactorsandtheseverityofthedrug-druginteraction
• Uponassessment,thecommunitypharmacistshould:• PlacethemedicationonholdiftheTdP riskishigh• Recommendbaselineandsteady-stateECGtesting(at5half-livesofthemedication)• Providealternativedrugtherapies,ordose-adjustbasedonthepatient’srenalorhepaticfunction
• DecisionshouldalwaysbedocumentedandsignsandsymptomsofTdP shouldbecommunicatedtothepatient• Point-of-careECGtestingmayaidcommunitypharmacistsintheassessmentofpatientsatriskforTdP
Citalopram Domperidone Ciprofloxacin§ HealthCanada/FDA:>40mg
shouldnotbeused(20mg forelderly)duetodose-dependentQTc prolongation.
§ CANMAT:SSRIscarryaverylowriskofTdP andotherarrhythmias.
§ Primary literature:mostshowedincreaseinQTc interval;Beachetalconsidered40mgasmaxdosetobeoverlyconservative.5
§ Health Canada: contraindicatedinQTc prolongation,maxdailydose30mg.
§ AAG:suggestbaselineECG.§ Primary literature:Boyceetaldemonstrated a 3-foldincreaseindomperidone concentrationswithconcomitantusewithaCYP3A4inhibitor(ketoconazole) andrecommendedthatthecombinationshouldnotbeadministered.6
• Health Canada/FDA:minimalguidance.
• CJU/CTS:nomention.• Primary literature:Tsikouris
etalobservedthatciprofloxacinistheleasttorsadogenicfluoroquinolone,andinhealthypatients,a7-daytreatmentdoesnotincreasetheriskforTdP.7
Table1.Resultsfromenvironmentalscanandsystematicreview.5-7
MEDLINE(PubMed)
Search criteria:(qt prolongationORprolongedqt ORqt
intervalORqtc intervalORlongqt syndrome)AND(citalopramORdomperidone OR
ciprofloxacin)222articles
Timeframe:2006– 2016,inclusive
156articles
153articlesPatients≥19yearsold
Randomizedcontrolledtrials,meta-analysesPre-programmed“AdditionalFilter”
criterionManualperusal
7articlestotal
Citalopram:5articles
Domperidone:1 articles
Ciprofloxacin:1article
1. ProlongedQ-Tinterval.MayoClinic.http://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/multimedia/prolonged-q-t-interval/img-20007972.AccessedDecember11,2016.
2. DrugsandHealthProducts.Notice– adoptionofICHguidance:TheclinicalevaluationofQT/QTc intervalprolongationandproarrhythmic potentialfornon-antiarrhythmicdrugs– ICHTopicE14.HealthCanada.http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ich/efficac/e14-eng.php.PublishedApril13,2006.AccessedOctober11,2016.
3. TisdaleJE.Drug-inducedQTintervalprolongationandtorsades depointes:Roleofthepharmacistinriskassessment,prevention,andmanagement.CanPharmJ.2016:149(3);139-152.
4. OverviewofLongQTSyndromeandTorsades dePointes.CredibleMeds.https://www.crediblemeds.org/healthcare-providers/practical-approach.RevisedNovember19,2015.AccessedNovember15,2016.
5. BeachS,KostisW,Celano C,etal.Meta-AnalysisofSelectiveSerotoninReuptakeInhibitor–AssociatedQTc Prolongation.JClin Psychiatry.2014;75(05):e441-e449.doi:10.4088/jcp.13r08672.
6. BoyceM,BaisleyK,WarringtonS.Pharmacokineticinteractionbetweendomperidone andketoconazoleleadstoQTprolongationinhealthyvolunteers:arandomized,placebo-controlled,double-blind,crossoverstudy.BritishJournalofClinicalPharmacology.2012;73(3):411-421.doi:10.1111/j.1365-2125.2011.04093.x.
7. Tsikouris JP,Peeters MJ,CoxCD,Meyerrose GE,SeifertCF.EffectofthreefluoroquinolonesonQTanalysisafterstandardtreatmentcourses.AnnNoninvasive Electrocardiol. 2006;11(1):52-56.doi:10.1111/j.1542-474X.2006.00082.x.
8. Celexa (citalopramhydrobromide)TabletsandOralSolution.U.S.Food&DrugAdministration.http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm271275.htm.PublishedDecember2012.AccessedDecember11,2016.
Contactinformation:TracyHe([email protected]) | Dec2016.Copyright©2016.PosterdesignbyTracyHe.
