Paxlovid Drug-Drug Interactions

Because ritonavir-boosted nirmatrelvir (Paxlovid) is the only highly ... Acetaminophen; Aspirin; Codeine; Ibuprofen; Meloxicam; Naproxen. HomeTherapiesAntiviralTherapyRitonavir-BoostedNirmatrelvir(Paxlovid)ClinicalDataTherapiesAntiviralTherapySummaryRecommendationsRemdesivirRitonavir-BoostedNirmatrelvir(Paxlovid)MolnupiravirInterferonsIvermectinTable:CharacteristicsofAntiviralAgentsAnti-SARS-CoV-2AntibodyProductsSummaryRecommendationsAnti-SARS-CoV-2MonoclonalAntibodiesCOVID-19ConvalescentPlasmaIVIG-SARS-CoV-2Table:CharacteristicsofAnti-SARS-CoV-2AntibodyProductsImmunomodulatorsSummaryRecommendationsCorticosteroidsInterleukin-6InhibitorsKinaseInhibitorsColchicineFluvoxamineGM-CSFInhibitorsIVIG-Non-SARS-CoV-2Interleukin-1InhibitorsTable:CharacteristicsofImmunomodulatorsAntithromboticTherapyConcomitantMedicationsSupplementsSummaryRecommendationsVitaminCVitaminDZincGuidelinePDFsSectionOnly(PDF|603KB)FullGuideline(PDF|3.8MB)SignUpForUpdatesEmailAddressSubmitRelatedContentGuidelinesArchiveHowtoCiteTheseGuidelinesDrug-DrugInteractionsBetweenRitonavir-BoostedNirmatrelvir(Paxlovid)andConcomitantMedicationsDrugInfoClinicalDataClinicalDataDrugInfoLastUpdated:September26,2022Ritonavir,astrongcytochromeP450(CYP)3A4inhibitorandaP-glycoproteininhibitor,iscoadministeredwithnirmatrelvirtoincreasethebloodconcentrationofnirmatrelvir,therebymakingiteffectiveagainstSARS-CoV-2.Ritonavirmayalsoincreasebloodconcentrationsofcertainconcomitantmedications.Becauseritonavir-boostednirmatrelvir(Paxlovid)istheonlyhighlyeffectiveoralantiviralforthetreatmentofCOVID-19,druginteractionsthatcanbesafelymanagedshouldnotprecludetheuseofthismedication.Cliniciansshouldbeawarethatmanycommonlyusedmedicationscanbesafelycoadministeredwithritonavir-boostednirmatrelvirdespiteitsdrug-druginteractionpotential.Box1includescommonlyprescribedmedicationsthatarenotexpectedtohaveclinicallyrelevantinteractionswithritonavir-boostednirmatrelvir.Box1.SelectOutpatientMedicationsNotExpectedtoHaveClinicallyRelevantInteractionsWithRitonavir-BoostedNirmatrelvir(Paxlovid)Thisisnotacomprehensivelistofallthemedicationsthatarenotexpectedtohaveclinicallyrelevantinteractionswithritonavir-boostednirmatrelvir.aBox1.SelectOutpatientMedicationsNotExpectedtoHaveClinicallyRelevantInteractionsWithRitonavir-BoostedNirmatrelvir(Paxlovid)MedicationsWithoutClinicallyRelevantInteractionsThesemedicationsmaybecoadministeredwithoutdoseadjustmentandwithoutincreasedmonitoring.aThislistisnotinclusiveofallnoninteractingmedicationswithineachdrugcategory.AcidreducersFamotidineOmeprazolePantoprazoleAllergyCetirizineDiphenhydramineFexofenadineLoratadineAnti-infectivesAzithromycinCidofovirHydroxychloroquineTecovirimatValacyclovirCardiovascularAspirinAtenololCarvedilolFurosemideHydrochlorothiazideIrbesartanIsosorbidedinitrateLisinoprilLosartanMetoprololPrasugrelDiabetesEmpagliflozinInsulinMetforminPioglitazoneImmunosuppressantsAbrocitinibBaricitinibMethotrexateMycophenolatePrednisoneLipid-modifiersEzetimibePitavastatinPravastatinMigraineFrovatriptanNaratriptanRizatriptanSumatriptanNeuropsychiatricAmitriptylineBupropionCitalopramDuloxetineEscitalopramFluoxetineGabapentinLorazepamNortriptylineOlanzapineParoxetineSertralineVenlafaxinePainAcetaminophenAspirinCodeineIbuprofenMeloxicamNaproxenRespiratoryCorticosteroids(inhaled)FormoterolMontelukastMiscellaneousAllopurinolContraceptives(oral)bCyclobenzaprineDonepezilEnoxaparinFinasterideLevothyroxineMostmonoclonalantibodyproductscOndansetrona ThislistisprimarilybasedonthemostcommonmedicationsearchesbyU.S.usersontheLiverpoolCOVID-19DrugInteractionswebsitebetweenJanuary1andJuly31,2022(internalcommunication,August2022).bTheFDAEUAforritonavir-boostednirmatrelvirsuggeststhatindividualswhousecontraceptiveproductscontainingethinylestradiolconsiderusingabackup,nonhormonalcontraceptivemethodbecausecoadministrationmayresultinlowethinylestradiollevels.However,thelowlevelisnotexpectedtobeclinicallysignificantduringthe5daysoftherapy.Theprogestinconcentrationofacombinedhormonalcontraceptiveisexpectedtoremainsimilarorincreasewithcoadministration,whichwouldmaintaintheeffectivenessoftheoralcontraceptive.cRitonavir-boostednirmatrelvirinteractswithcertainconjugatedmonoclonalantibodies,suchasthoseconjugatedtothedrugmonomethylauristatinE(orvedotin).Theseincludebrentuximabvedotin,enfortumabvedotin,polatuzumabvedotin,andtisotumabvedotin.Beforecoadministeringritonavir-boostednirmatrelvirandanyoftheseconjugatedmonoclonalantibodies,refertothedrug’sFDAprescribinginformationandconsultwiththepatient’sspecialistprovidersasneeded. Key:EUA=EmergencyUseAuthorization;FDA=FoodandDrugAdministrationMedicationsThatHaveClinicallyRelevantDrug-DrugInteractionsWithRitonavir-BoostedNirmatrelvirCliniciansshouldbeawarethat,insomecases,drug-druginteractionswithritonavir-boostednirmatrelvirmayleadtoseriousorlife-threateningdrugtoxicities.Therecommendedtreatmentcourseofritonavir-boostednirmatrelvirforCOVID-19is5days.Afterthelastdoseisadministered,mostoftheinteractionpotentialresolveswithin2to3days,althoughresolutionmaytakelongerinadultsofadvancedage.1Longertreatmentcoursesofritonavir-boostednirmatrelvirarenotauthorizedbythecurrentFoodandDrugAdministration(FDA)EmergencyUseAuthorization(EUA),andthereareinsufficientdataontheefficacyofadministeringasecondtreatmentcourseincaseswhereSARS-CoV-2viralreboundissuspected.Theguidanceinthisdocumentisbasedonthedrug-druginteractionpotentialoftheFDA-authorized5-daycourseofritonavir-boostednirmatrelvir.Ritonavir-boostednirmatrelvirshouldnotbegivenwithin2weeksofadministeringastrongCYP3A4inducer(e.g.,St.John’swort,rifampin).Ritonavir-boostednirmatrelviriscontraindicatedinthissetting,becausestrongCYP3A4inducersmayreducetheconcentrationsofnirmatrelvirandritonavir,renderingthetreatmentineffectiveagainstSARS-CoV-2.AlternativetreatmentforCOVID-19shouldbeprescribed.IdentifyingDrug-DrugInteractionsBeforeprescribingritonavir-boostednirmatrelvir,carefullyreviewthepatient’sconcomitantmedications,includingover-the-countermedicines,herbalsupplements,andrecreationaldrugs.Consult1ormoreofthefollowingresourcesforinformationonidentifyingandmanagingdrug-druginteractions:Quickreferencelists:Box1listsselectoutpatientmedicationsthatarenotexpectedtohaveclinicallyrelevantinteractionswithritonavir-boostednirmatrelvir.Box2listsselectoutpatientmedicationsthathaveclinicallyrelevantdrug-druginteractionswithritonavir-boostednirmatrelvir.Web-baseddrug-druginteractionchecker:The LiverpoolCOVID-19DrugInteractionswebsiteTableswithguidanceonmanagingspecificdrug-druginteractions:TheOntarioCOVID-19ScienceAdvisoryTableTheFDAEUAfactsheetandchecklistforritonavir-boostednirmatrelvirConsiderconsultingwithanexpert(e.g.,withapharmacist,anHIVspecialist,orthepatient’sspecialistproviders),especiallyforpatientsreceivinghighlyspecializedtherapiesordrugspronetoconcentration-dependenttoxicities,suchascertainanticonvulsant,anticoagulant,antiarrhythmic,chemotherapeutic,neuropsychiatric,andimmunosuppressantdrugs.ManagementStrategiesforDrug-DrugInteractionsConsiderthemagnitudeandsignificanceofthepotentialdrug-druginteractionwhenchoosingmanagementstrategiesforpatientswhowillbereceivingritonavir-boostednirmatrelvir.Potentialstrategiesinclude:Increasingmonitoringforpotentialadversereactionstotheconcomitantmedication.Adjustingthedoseoftheconcomitantmedication.Temporarilywithholdingtheconcomitantmedication.Usinganalternativetotheconcomitantmedication.UsingalternativeCOVID-19therapies(seeTherapeuticManagementofNonhospitalizedAdultsWithCOVID-19).Usethechosenstrategyforthe5-daydurationofritonavir-boostednirmatrelvirtreatmentandforatleast2to3daysaftertreatmentcompletion.Thestrategymayneedtocontinueforalongerdurationifritonavir-boostednirmatrelvirisinitiatedinanadultofadvancedageoriftheinteractingmedicationhasalonghalf-life.Patientsshouldbecounseledaboutritonavir-boostednirmatrelvir’sdrug-druginteractionpotentialandthesignsandsymptomsofpotentialadverseeffects.Ifritonavir-boostednirmatrelvirisprescribedtopatientswhotakecertainrecreationaldrugs,thosepatientswillrequirecounselingandcarefulmonitoringforadverseeffects.Box2.SelectOutpatientMedicationsThatHaveClinicallyRelevantDrug-DrugInteractionsWithRitonavir-BoostedNirmatrelvir(Paxlovid)Notallmedicationsthatmayinteractwithritonavir-boostednirmatrelvirareincludedinBox2.Deviationfromtherecommendedstrategiesmaybeappropriateincertainclinicalscenarios.Box2.SelectOutpatientMedicationsThatHaveClinicallyRelevantDrug-DrugInteractionsWithRitonavir-BoostedNirmatrelvir(Paxlovid)PrescribeAlternativeCOVID-19TherapyForthesemedications,managementstrategiesarenotpossibleorfeasible,ortherisksoutweighthepotentialbenefits.AnticonvulsantsCarbamazepinePhenobarbitalPhenytoinPrimidoneAnti-infectivesGlecaprevir/pibrentasvirRifampinRifapentineImmunosuppressantsVoclosporinCardiovascularAmiodaroneClopidogrela,bDisopyramideDofetilideDronedaroneEplerenoneFlecainideIvabradinePropafenoneQuinidineNeuropsychiatricClozapineLurasidoneMidazolam(oral)PimozidePulmonaryhypertensionSildenafilTadalafilVardenafilMiscellaneousBosentanCertainchemotherapeuticagentscErgotderivativesLumacaftor/ivacaftorSt.John’swortTolvaptanTemporarilyWithholdConcomitantMedication,ifClinicallyAppropriateWithholdthesemedicationsduringritonavir-boostednirmatrelvirtreatmentandforatleast2–3daysaftertreatmentcompletion.Theymayneedtobewithheldforlongerifthepatientisanadultofadvancedageorthemedicationhasalonghalf-life.Ifwithholdingisnotclinicallyappropriate,useanalternativeconcomitantmedicationorCOVID-19therapy.AnticoagulantsRivaroxabandAnti-infectivesErythromycinBPHAlfuzosinSilodosinCardiovascularAliskirenRanolazineTicagrelorbVorapaxarImmunosuppressantseEverolimusSirolimusTacrolimusLipid-modifiersAtorvastatinfLomitapideLovastatinfRosuvastatinfSimvastatinfMigraineEletriptanRimegepantUbrogepantNeuropsychiatricSuvorexantTriazolamgErectiledysfunctionAvanafilRespiratorySalmeterolMiscellaneousCertainchemotherapeuticagentscColchicinehFinerenoneFlibanserinNaloxegolAdjustConcomitantMedicationDoseandMonitorforAdverseEffectsConsulttheLiverpoolCOVID-19DrugInteractionswebsiteortheOntarioCOVID-19ScienceAdvisoryTableforspecificdosingrecommendations.iIfthedoseoftheconcomitantmedicationcannotbeadjusted,withholdthemedication(ifclinicallyappropriate)oruseanalternativeconcomitantmedicationorCOVID-19therapy.AnticoagulantsApixabanDabigatranEdoxabanAnti-infectivesClarithromycinItraconazoleKetoconazoleMaravirocRifabutinBPHTamsulosinCardiovascularCilostazolDigoxinMexiletineDiabetesSaxagliptinErectiledysfunctionSildenafilTadalafilVardenafilImmunosuppressantsCyclosporineeDexamethasonejFedratinibRuxolitinibTofacitinibUpadacitinibMigraineAlmotriptanhNeuropsychiatricAlprazolamgAripiprazoleBrexpiprazoleBuspironeCariprazineChlordiazepoxidegClobazamgClonazepamgClorazepategDiazepamgEstazolamgFlurazepamgIloperidoneLumateperonePimavanserinQuetiapineTrazodonePainFentanylHydrocodoneOxycodonePulmonaryhypertensionRiociguatMiscellaneousCertainchemotherapeuticagentscDarifenacinElexacaftor/tezacaftor/ivacaftorEluxadolineIvacaftorSolifenacinTezacaftor/ivacaftorContinueConcomitantMedicationandMonitorforAdverseEffectsPre-emptivedoseadjustmentisnotrequiredbutmaybeconsideredbasedonanindividualizedassessmentofthepatient’sriskforadversereactions.Educatepatientsaboutpotentialadverseeffects.ConsulttheLiverpoolCOVID-19DrugInteractionswebsiteortheOntarioCOVID-19ScienceAdvisoryTableformonitoringguidanceanddoseadjustmentinformationasneeded.iAnticoagulantsWarfarinAnti-infectivesBrincidofovirkCobicistat-orritonavir-boostedantiretroviralsIsavuconazolePosaconazoleVoriconazoleBPHDoxazosinTerazosinDiabetesGlyburideCardiovascularAmlodipineDiltiazemFelodipineNifedipineSacubitrilValsartanVerapamilMigraineZolmitriptanNeuropsychiatricHaloperidolHydroxyzineMirtazapineRisperidoneZiprasidoneZolpidemPainBuprenorphineHydromorphoneMethadoneMorphineTramadolMiscellaneousCertainchemotherapeuticagentscCertainconjugatedmonoclonalantibodieslOxybutyninaReducedeffectivenessofclopidogrelislikely.Itmaybeacceptabletocontinueclopidogrelifthebenefitsofusingritonavir-boostednirmatrelviroutweightheriskofreducedclopidogreleffectiveness.bForpatientsatveryhighriskofthrombosis(e.g.,thosewhoreceivedacoronarystentwithinthepast6weeks),considerprescribinganalternativeantiplatelet(e.g.,prasugrel,ifclinicallyappropriate)oranalternativeCOVID-19therapy.cRitonavir-boostednirmatrelvirmayincreaseconcentrationsofsomechemotherapeuticagents,leadingtoanincreasedpotentialfordrugtoxicities.Somechemotherapeuticagentsmaydecreasetheeffectivenessofritonavir-boostednirmatrelvir.PleaserefertotheFDAEUAfactsheetforritonavir-boostednirmatrelvirandtheprescribinginformationforthechemotherapeuticagentandconsultthepatient’sspecialistprovider.TheUniversityHealthNetwork/KingstonHealthSciencesCentreisanadditionalresourceforevaluatingdrug-druginteractionsforchemotherapeuticagents.dForpatientswhoareathighriskofarterialorvenousthrombosis(e.g.,thosewhohadastrokewithinthepast3monthswithaCHA2DS2-VAScscoreof7–9orapulmonaryembolismwithinthepastmonth),consulttheprimaryorspecialtyproviderandconsiderusinganalternativeanticoagulantsuchasLMWHoranalternativeCOVID-19therapy.Forpatientswithalowerriskforarterialorvenousthrombosis,cliniciansmayconsideradministeringlow-doseaspirinwhilerivaroxabanisbeingwithheld.eTheuseofanotherCOVID-19therapymayneedtobeconsidered.Theseimmunosuppressantshavesignificantdrug-druginteractionpotentialwithritonavir,andtheyshouldnotbeusedifclosemonitoring,includingtherapeuticdrugmonitoring,isnotfeasible.Consultapatient’sspecialistprovidersbeforecoadministeringtheseimmunosuppressantsandritonavir-boostednirmatrelvir.SeetheAmericanSocietyofTransplantationstatementformoreinformation.fWithholdlovastatinandsimvastatinforatleast12hoursbeforeinitiatingritonavir-boostednirmatrelvir,duringtreatment,andfor5daysaftertreatmentcompletion.Withholdatorvastatinandrosuvastatinatthebeginningoftreatmentwithritonavir-boostednirmatrelvirandresumeaftercompletionofthe5-daycourse.Ifwithholdingastatinisnotclinicallyappropriate(e.g.,thepatienthadarecentmyocardialinfarction),thedosesofatorvastatinandrosuvastatincanbeadjustedandcontinued,andlovastatinandsimvastatinshouldbeswitchedtoanalternativestatin.gTheguidanceonmanagingdrug-druginteractionsbetweencertainbenzodiazepinesandritonavir-boostednirmatrelvircanvarysignificantlybetweenresources.TheguidanceinthistableisbasedontheFDAEUAfactsheetforritonavir-boostednirmatrelvir.Notethatabruptdiscontinuationorrapiddosereductionofbenzodiazepinesmayprecipitateanacutewithdrawalreaction.2Theriskisgreatestforpatientswhohavebeenusinghighdosesofbenzodiazepinesoveranextendedperiod.hForpatientswithhepaticorrenalimpairment,donotcoadministerthismedicationwithritonavir-boostednirmatrelvir.iFormedicationsthatarenotincludedontheLiverpoolCOVID-19DrugInteractionswebsiteortheOntarioCOVID-19ScienceAdvisoryTable,refertotheFDAlabelsforinformationoncoadministeringthesemedicationswithritonavirorotherstrongCYP3A4and/orP-gpinhibitors.jDexamethasoneexposureisexpectedtoincrease2.60-foldwhendexamethasoneiscoadministeredwithritonavir-boostednirmatrelvir.3Cliniciansshouldweightherisksandbenefitsofcontinuingthepatient’snormaldoseofdexamethasone(whilemonitoringforAEs)versusdecreasingthedose.PatientswhoarereceivinghigherdosesofdexamethasonewillbeatagreaterriskofAEs.kPatientsshouldtakeritonavir-boostednirmatrelviratleast3hoursafterreceiptofbrincidofovir.lRitonavir-boostednirmatrelvirinteractswithcertainconjugatedmonoclonalantibodies,suchasthoseconjugatedtothedrugmonomethylauristatinE(orvedotin).Theseincludebrentuximabvedotin,enfortumabvedotin,polatuzumabvedotin,andtisotumabvedotin.Beforecoadministeringritonavir-boostednirmatrelvirandanyoftheseconjugatedmonoclonalantibodies,refertothedrug’sFDAprescribinginformationandconsultwiththepatient’sspecialistprovidersasneeded. Key: AE=adverseeffect;BPH=benignprostatichyperplasia;CHA2DS2-VASc=congestiveheartfailure,hypertension,age,diabetes,stroke,vasculardisease;CYP=cytochromeP450;EUA=EmergencyUseAuthorization;FDA=FoodandDrugAdministration;LMWH=low-molecular-weightheparin;P-gp=P-glycoproteinReferencesStaderF,KhooS,StoeckleM,etal.Stoppinglopinavir/ritonavirinCOVID-19patients:durationofthedruginteractingeffect.JAntimicrobChemother.2020;75(10):3084-3086.Availableat:https://www.ncbi.nlm.nih.gov/pubmed/32556272.FoodandDrugAdministration.FDArequiringBoxedWarningupdatedtoimprovesafeuseofbenzodiazepinedrugclass.2020.Availableat:https://www.fda.gov/media/142368/download.LiM,ZhuL,ChenL,LiN,QiF.Assessmentofdrug-druginteractionsbetweenvoriconazoleandglucocorticoids.JChemother.2018;30(5):296-303.Availableat:https://www.ncbi.nlm.nih.gov/pubmed/30843777.GuidelinePDFsSectionOnly(PDF|603KB)FullGuideline(PDF|3.8MB)SignUpForUpdatesEmailAddressSubmitRelatedContentGuidelinesArchiveHowtoCiteTheseGuidelinesBacktoTop