DRUGMONOGRAPH

Lovastatin
Altoprev|Mevacor

DrugInformationProvidedByGoldStandard

Description:LovastatinisanoralantilipemicagentproducedbyfermentationofAspergillusterreus.LovastatinrepresentsthefirstHMG
CoAreductaseinhibitortobeintroduced.Lovastatinwasdevelopedasaprodrugtoconcentrateactivedrugintheliverduringfirstpass
circulation.Simvastatinisalsoaprodrug,butpravastatinandfluvastatinarenot.Lovastatin(Mevacor)dosesof1080mg/day,givenin12
divideddoses,resultinmeanLDLreductionsrangingfrom2142%.Lovastatin(Mevacor)wasapprovedbytheFDAforthetreatmentof
hypercholesterolemiainAugust1987.Sincethattime,itsindicationshavebeenexpandedtoincludeslowingtheprogressionofcoronary
atherosclerosis,primaryprevention(myocardialinfarctionprophylaxis),andstrokeprophylaxis.IntheAFCAPS/TexCAPSprimary
preventionstudy,lovastatinreducedtheriskforthefirstacutemajorcoronaryeventinadultmenandwomenwithaveragetotalandLDL
cholesterollevelsandbelowaverageHDLcholesterollevels.25813Afteranaverageof5.2years,lovastatinreducedtheincidenceoffirstacute
majorcoronaryeventby37%,fatalornonfatalmyocardialinfarctionby40%,unstableanginaby32%,andcoronaryrevascularization
proceduresby33%,respectively.25813Additionally,alargeretrospectivestudydemonstratedthatcontinuationofstatintherapyprovidesan
ongoingreductioninallcausemortalityinpatientswithandwithoutknowncoronaryheartdisease(CHD),withthegreatestriskreduction
amongpatientswithabaselineLDLC>=190mg/dlandpatientsinitiatedonhigherefficacystatins(i.e.,simvastatin,pravastatin,or
lovastatin80mg/dayatorvastatin>=20mg/dayrosuvastatin>=10mg/day).Amongpatientswithaproportionofdayscovered(PDC)of
>=90%,determinedbythenumberofstatinprescriptionsdispensedduringthetimebetweenthefirststatinprescriptionandtheendof
followup,therewasa45%and51%lowermortalityriskintheprimary(patientswithoutknownCHD)andsecondary(patientswithknown
CHD)preventiongroups,respectively,comparedtopatientswithaPDC<=10%.Themeanlengthoffollowupwas4and5yearsinthe
primaryandsecondarypreventiongroups,respectively,withamaximumlengthoffollowupof9.5years.34872Severalgenericequivalentsfor
MevacorwereapprovedinDecember,2001.Advicor(seeseparatemonograph),acombinationproductforlovastatinandniacin,was
approvedbytheFDAinDecember,2001.TheFDAapprovedanextendedreleaseformulationoflovastatin,Altocor,onJune26,2002.The
proprietarynameforAltocorlovastatinextendedreleasetabletswaschangedtoAloprevbytheFDAonJuly21,2004.AnFDAadvisory
committeevoted20to3againstmarketinglovastatin20mgasanOTCproductduringJanuary2005.Althoughfavorableresultswere
reportedbythemanufacturersponsoredCUSTOMstudyinregardtoOTClovastatinuse3070630707,theFDAadvisorycommitteeraised
concernsofinappropriateselfselection(selfdiagnosis)bythestudyparticipants.InDecember2007,anFDAadvisorypanelagainvoted10
to2againsttheOTCmarketingoflovastatincitingconcernthatpatientswouldnotbeabletoproperlyfollowinstructionstosafelyuse
lovastatinwithoutaprescription.

MechanismofAction:Lovastatinisaprodrugwithlittleornoinherentactivitybutishydrolyzedinvivotomevinolinicacid.Mevinolinic
acid,oneoflovastatin'sseveralactivemetabolites,isstructurallysimilartoHMGCoA(hydroxymethylglutarylCoA).Oncehydrolyzed,
lovastatincompeteswithHMGCoAforHMGCoAreductase,ahepaticmicrosomalenzyme.Interferencewiththeactivityofthisenzyme
reducesthequantityofmevalonicacid,aprecursorofcholesterol.Thisprocessoccurswithinthehepatocyteandisoneoftwomechanisms
thatgeneratecholesterol.CholesterolalsocanbetakenupfromLDLbyendocytosis.Sincedenovosynthesisofcholesterolisimpairedby
lovastatin,thesecondmechanismisaugmented.Thus,lovastatinalsoenhancesclearanceofLDL.Lovastatinexertsitseffectsmainlyontotal
cholesterolandLDL,withminoreffectsseenonHDLandtriglycerides.Becausepeakcholesterolsynthesisoccursintheearlymorninghours,
eveningdosingforlovastatinispreferable.

HMGCoAreductaseinhibitorshavebeenreportedtodecreaseendogenousCoQ10serumconcentrationstheclinicalsignificanceofthese
effectsisunknown.

Pharmacokinetics:Lovastatinisadministeredorally.Bothlovastatinanditsbetahydroxyacidmetabolitearehighlyboundtoplasma
proteins(>95%).Lovastatincrossesthebloodbrainbarrierandtheplacentalbarrier,andmaybedistributedintohumanmilk.Lovastatinis
aprodrugthatishydrolyzedtomevinolinicacidandmetabolizedtoseveralotheractivederivativesviahepaticCYP3A4isoenzymes.The
majoractivemetabolitespresentinhumanplasmaarethebetahydroxyacid(lovastatinacid),its6'hydroxyderivative,andtwoadditional
metabolites.Theplasmahalflifeofmevinolinicacidisabout1.11.7hours.Followingasingledoseofimmediatereleaselovastatintoadults
withhypercholesterolemia,83%isexcretedinthefecesasbothactiveandinactivemetabolites.Drugeliminatedviathestoolrepresentsboth
unabsorbeddruganddrugandmetabolitessecretedinthebile.Only10%ofadoseiseliminatedrenally.

AffectedcytochromeP450isoenzymesanddrugtransporters:CYP3A4,Pgp
LovastatinisasubstrateofCYP3A4hepaticmetabolism,butdoesnotaffectthemetabolismofCYP3A4substrates.2860428774Ithasmultiple
significantdruginteractionswithCYP3A4inhibitors,whichmayresultinincreasedHMGCoAreductaseinhibitionandtoxicityincluding
myopathyandrhabdomyolysis.LovastatinisalsoasubstrateandinhibitorofPglycoprotein(Pgp)transport.3449241275286042877441275

RouteSpecificPharmacokinetics
OralRoute
LovastatinisincompletelyabsorbedfromtheGItractandundergoesextensivefirstpassextractionintheliver.Lovastatinwaspurposely
developedasaprodrugtoconcentrateactiveinhibitorsintheliverduringfirstpasscirculation.Only<5%(withconsiderableinterindividual
variation)ofactiveinhibitorsreachesthesystemiccirculationfollowingimmediatereleaselovastatin.Peakconcentrationsofactiveandtotal
HMGCoAreductaseinhibitorsoccurwithin24hoursafteroraladministrationofimmediatereleaselovastatin.Thepresenceoffoodinthe
GItractenhancesoralabsorption.Lovastatinabsorptionappearstobeincreasedbyatleast30%bygrapefruitjuicehowever,theeffectis
dependentontheamountofgrapefruitjuiceconsumedandtheintervalbetweengrapefruitjuiceandlovastatiningestion.Whencomparedto
40mgofimmediatereleaselovastatin,Altoprev40mg(extendedreleaselovastatin)producesa3.9%greaterLDLreduction.27109Atthe
samedosage(40mg),Altoprevisalsoassociatedwithgreaterlovastatin(prodrug)bioavailability,alowerlovastatinCmax,prolonged
absorption(increasedTmax),comparableexposuretothelovastatinacidmetabolite,andsimilarexposuretoactiveandtotalinhibitorsof
HMGCoAreductase.27109FooddecreasesthebioavailabilityofAltoprev.WhenAltoprevisgivenwithameal,plasmaconcentrationsof
lovastatinandlovastatinacidareabout0.5to0.6timesthoseobservedwhenadministeredinthefastingstate.Diurnalvariationin
cholesterolsynthesishasbeendocumentedsingledailydosesoflovastatin(immediatereleaseorextendedreleaseformulations)aremost
effectivewhengivenintheevening.23668

SpecialPopulations
RenalImpairment
Inpatientswithsevererenalimpairment(CrCl1030ml/min),theplasmaconcentrationsoftotalinhibitorsafterasingledoseoflovastatin
areapproximatelytwofoldhigherthanthoseinhealthyvolunteers.Thedialyzabilityoflovastatinoritsmetabolitesisunknown.

Geriatric
Elderlypatientsreceivingimmediatereleaselovastatinhavebeenreportedtohave45%highermeanplasmalevelsofHMGCoAreductase
inhibitoryactivityvs.youngerpatients.

Lastrevised:June13,2017

Indications&Dosage
atherosclerosis

hypercholesterolemia

hyperlipoproteinemia

myocardialinfarctionprophylaxis

strokeprophylaxis

Forthetreatmentofprimaryhypercholesterolemia,specificallyhyperlipoproteinemiatypesIIaorIIb,inpatients
unresponsivetodietarycontrol:
Oraldosage(immediatereleasetablets):
Adults:Initially,10to20mgPOoncedailywiththeeveningmeal.PatientsrequiringLDLreductionsof20%ormoretoachievetheirgoal
maybeginwith20mgPOoncedaily,whilepatientsrequiringlowerreductionsmaybeginwith10mgPOoncedaily.Therecommended
dosingrangeis10to80mg/dayPOinsingleor2divideddoses.Themaximumdailydoseis80mg/dayPO.Atadosagerangeof10to80
mg/day,themeanLDLreductionrangeis21%to42%.Dividingthedailydosageinto2dosesisslightlymoreeffectivethanoncedailydosing.
23471Dosageadjustmentsshouldbemadeatintervalsof4weeksormore.AdjustdosagetoattainthetargetLDLandlipidgoalsbasedonthe

NCEPguidelines.2599430125GeriatricpatientsmayhavegreaterLDLreductionsattheusualdosecomparedtoyoungeradults.28604
Adultstakingdanazol,diltiazem,orverapamil:Initially,10mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.28604
Adultstakingamiodarone:Initially,10to20mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.28604
AdolescentsandChildren10yearsandolderincludinggirlswhoareatleast1yearpostmenarche:Initially,10to20mgPOoncedailywith
theeveningmeal.PatientsrequiringreductionsinLDLcholesterolof20%ormoretoachievetheirgoalcanbestartedat20mgPOoncedaily,
whilepatientsrequiringlowerreductionsmaybeginwith10mgPOoncedaily.Maximumdosageis40mg/dayPO.Dosageadjustments
shouldbemadeatintervalsof4weeksormore.AdjustdosagetoattainthetargetLDLandlipidgoals.3219533319NOTE:Lovastatinmaybe
usedasanadjuncttodietinadolescentsandchildren10yearsandolder(includinggirlsatleast1yearpostmenarche)wheneither:1)the
LDLremains190mg/dLorhigheror2)theLDLremainshigherthan160mg/dLandthereisanincreasedriskforcardiovasculardisease
(e.g.,positivefamilyhistoryofprematurecardiovasculardiseaseor2ormoreotherriskfactorsarepresent).
Oraldosage(lovastatinextendedreleasetabletsAltoprev):
Adults:Initially,20to60mgPOoncedaily(meanLDLreductionrange:30%to41%),givenintheeveningatbedtime.Foodreduces
absorptionoftheextendedreleasetablets.ForpatientsrequiringsmallerLDLreductions,lovastatinextendedreleaseisnotrecommended
immediatereleaselovastatinshouldbeconsidered.Dosageadjustmentsshouldbemadeatintervalsof4weeksormore.43289Adjustdosage
toattainthetargetLDLandlipidgoalsbasedontheNCEPguidelines.2599430125
Adultstakingdanazol,diltiazem,orverapamil:20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.43289
Adultstakingamiodarone:Initially,20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.43289
GeriatricorPatientswithcomplicatedmedicalconditions(e.g.,renalinsufficiency,diabetes):Themanufacturerrecommends20mgPO
oncedaily,givenintheeveningatbedtime.Higherdosesshouldbeusedonlyaftercarefulconsiderationofthepotentialrisksandbenefits.
Forpatientsrequiringsmallercholesterolreductions,theextendedreleasedosageformisnotrecommendedimmediatereleaselovastatin
shouldbeconsidered.43289

Forslowingtheprogressionofcoronaryatherosclerosis:
Oraldosage(immediatereleasetablets):
Adults:Initially,20mgPOoncedailywiththeeveningmeal.Therecommendeddosingrangeis10to80mg/dayPOinsingleor2divided
doses.Themaximumdailydoseis80mg/dayPO.28604Attheusualdosagerangeof20to80mg/dayPO,themeanLDLreductionrangeis
27%to42%.Dosageadjustmentsshouldbemadeatintervalsof4weeksormoretoattainthetargetLDLandlipidgoalsbasedontheNCEP
guidelines.2599430125Inpatientswithcoronaryarterydisease,astudyoflovastatin80mg/daysignificantlyreducedcoronaryarterystenosis.
23587
GeriatricpatientsmayhavegreaterLDLreductionsattheusualdosecomparedtoyoungeradults.
Adultstakingdanazol,diltiazem,orverapamil:Initially,10mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.28604
Adultstakingamiodarone:Initially,20mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.28604
Oraldosage(lovastatinextendedreleasetabletsAltoprev):
Adults:Initially,20to60mgPOoncedaily(meanLDLreductionrange:30%to41%),givenintheeveningatbedtime.Foodreduces
absorptionoftheextendedreleasetablets.ForpatientsrequiringsmallerLDLreductions,lovastatinextendedreleasetabletsarenot
recommendedimmediatereleaselovastatinshouldbeconsidered.Dosageadjustmentsshouldbemadeatintervalsof4weeksofmore.43289
AdjustdosagetoattainthetargetLDLandlipidgoalsbasedontheNCEPguidelines.2599430125
Adultstakingdanazol,diltiazem,orverapamil:20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.43289
Adultstakingamiodarone:Initially,20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.43289
GeriatricorPatientswithcomplicatedmedicalconditions(e.g.,renalinsufficiency,diabetes):Initially,20mgPOoncedailygiveninthe
eveningatbedtime.Higherdosesshouldbeusedonlyaftercarefulconsiderationofthepotentialrisksandbenefits.Forpatientsrequiring
smallercholesterolreductions,theextendedreleasedosageformisnotrecommendedimmediatereleaselovastatinshouldbeconsidered.
43289

Forslowingtheprogressionofatherosclerosisinpatientswithcarotidarterydisease(i.e.,strokeprophylaxis):
Oraldosage(immediatereleasetablets):
Adults:Initially,20mgPOoncedailywiththeeveningmeal.Therecommendeddosingrangeis10to80mg/dayPOinsingleor2divided
doses.Themaximumdailydoseis80mg/dayPO.28604Attheusualdosagerangeof20to80mg/dayPO,themeanLDLreductionrangeis
27%to42%.Dosageadjustmentsshouldbemadeatintervalsof4weeksormoretoattainthetargetLDLandlipidgoalsbasedontheNCEP
guidelines.2599430125Lovastatin,indosesof20to40mgPOperday,wascomparedwithlowdosewarfarininpatientswithearlycarotid
disease.Lovastatinwasshowntosignificantlyreducecardiovasculareventswhichincludedcoronaryheartdiseasedeath,stroke,andnon
fatalmyocardialinfarction.Althoughthesecardiovasculareventswereanalyzedcollectivelyandthereforenodirectconclusionscanbedrawn
regardingstrokeprophylaxisspecifically,thisstudyfocusedonpatientswithdocumentedcarotiddiseaseandtheresultingchangeinmean
carotidarteryintimalmedialthicknessinthecarotidartery.Allpatientswereencouragedtotakeaspirindaily.24359Geriatricpatientsmay
havegreaterLDLreductionsatusualdosescomparedtoyoungeradults.
Adultstakingdanazol,diltiazem,orverapamil:Initially,10mgPOoncedailywitheveningmeal.Becauseoftheriskofdevelopingmyopathy
and/orrhabdomyolysis,donotexceed20mg/dayPO.28604
Adultstakingamiodarone:Initially,20mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.28604
Oraldosage(lovastatinextendedreleasetabletsAltoprev):
Adults:Initially,20to60mgPOoncedaily(meanLDLreductionrange:30%to41%),givenintheeveningatbedtime.Foodreduces
absorptionoftheextendedreleasetablets.ForpatientsrequiringsmallerLDLreductions,lovastatinextendedreleaseisnotrecommended
immediatereleaselovastatinshouldbeconsidered.Dosageadjustmentsshouldbemadeatintervalsof4weeksormore.43289Adjustdosage
toattainthetargetLDLandlipidgoalsbasedontheNCEPguidelines.2599430125
Adultstakingdanazol,diltiazem,orverapamil:20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.43289
Adultstakingamiodarone:Initially,20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.43289
GeriatricorPatientswithcomplicatedmedicalconditions(e.g.,renalinsufficiency,diabetes):20mgPOoncedailygivenintheeveningat
bedtime.Higherdosesshouldbeusedonlyaftercarefulconsiderationofthepotentialrisksandbenefits.Forpatientsrequiringsmaller
cholesterolreductions,theextendedreleasedosageformisnotrecommendedimmediatereleaselovastatinshouldbeconsidered.43289

Formyocardialinfarctionprophylaxis(primaryprevention):
Oraldosage(immediatereleasetablets):
Adults:Initially,20to40mgPOoncedailywiththeeveningmeal.25813Therecommendeddosingrangeis10to80mg/dayPOinsingleor2
divideddoses.Themaximumdailydoseis80mg/dayPO.Attheusualdosagerangeof20to80mg/dayPO,themeanLDLreductionrangeis
27%to42%.Dosageadjustmentsshouldbemadeatintervalsof4weeksormoretoattainthetargetLDLandlipidgoalsbasedontheNCEP
guidelines.2599430125IntheAFCAPS/TexCAPSprimarypreventionstudy,lovastatinreducedtheriskforthefirstacutemajorcoronaryevent
inadultmenandwomenwithaveragetotalandLDLcholesterollevelsandbelowaverageHDLcholesterollevels.Afteranaverageof5.2
years,lovastatinreducedtheincidenceoffirstacutemajorcoronaryeventby37%,fatalornonfatalmyocardialinfarctionby40%,unstable
anginaby32%,andcoronaryrevascularizationproceduresby33%,respectively.25813GeriatricpatientsmayhavegreaterLDLreductionsat
usualdosescomparedtoyoungeradults.28604
Adultstakingdanazol,diltiazem,orverapamil:Initially,10mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.28604
Adultstakingamiodarone:Initially,20to40mgPOoncedailywiththeeveningmeal.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.28604
Oraldosage(lovastatinextendedreleasetabletsAltoprev):
Adults:Initially,20to60mgPOoncedaily(meanLDLreductionrange:30%to41%),givenintheeveningatbedtime.Foodreduces
absorptionoftheextendedreleasetablets.Forpatientsrequiringsmallercholesterolreductions,theextendedreleasedosageformisnot
recommendedimmediatereleaselovastatinshouldbeconsidered.Dosageadjustmentsshouldbemadeatintervalsof4weeksormore.43289
AdjustdosagetoattainthetargetLDLandlipidgoalsbasedontheNCEPguidelines.2599430125
Adultstakingdanazol,diltiazem,orverapamil:20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdeveloping
myopathyand/orrhabdomyolysis,donotexceed20mg/dayPO.43289
Adultstakingamiodarone:Initially,20mgPOoncedailygivenintheeveningatbedtime.Becauseoftheriskofdevelopingmyopathyand/or
rhabdomyolysis,donotexceed40mg/dayPO.43289
GeriatricorPatientswithcomplicatedmedicalconditions(e.g.,renalinsufficiency,diabetes):20mgPOoncedailygivenintheeveningat
bedtime.Higherdosesupto60mg/dayshouldbeusedonlyaftercarefulconsiderationofthepotentialrisksandbenefits.Forpatients
requiringsmallercholesterolreductions,theextendedreleasedosageformisnotrecommendedimmediatereleaselovastatinshouldbe
considered.43289

MaximumDosageLimits:
Adults
80mg/dayPOimmediatereleasetablets(e.g.,Mevacor)60mg/dayPOextendedreleasetablets(Altoprev).Max20mg/dayPOimmediate
releaseorextendedreleaselovastatiniftakingfibrates,niacin,danazol,orcyclosporinemax40mg/dayPOimmediatereleaselovastatinif
takingamiodaroneorverapamilmax20mg/dayPOextendedreleaselovastatiniftakingamiodaroneorverapamil.
Elderly
80mg/dayPOimmediatereleasetablets(e.g.,Mevacor)60mg/dayPOextendedreleasetablets(Altoprev).Max20mg/dayPOimmediate
releaseorextendedreleaselovastatiniftakingfibrates,niacin,danazol,orcyclosporinemax40mg/dayPOimmediatereleaselovastatinif
takingamiodaroneorverapamilmax20mg/dayPOextendedreleaselovastatiniftakingamiodaroneorverapamil.
Adolescents
40mg/dayPOimmediatereleasetablets(e.g.,Mevacor).
Children
>=10years:40mg/dayPOimmediatereleasetablets(e.g.,Mevacor).
<10years:Safetyandefficacyhavenotbeenestablished.

PatientswithHepaticImpairmentDosing
Notrecommendedinpatientswithhepaticdisease(seeContraindications).

PatientswithRenalImpairmentDosing
CrCl>=30ml/min:Nodosageadjustmentneeded.
CrCl<30ml/min:Usingdosages>20mg/dayshouldbecarefullyconsidered.

Intermittenthemodialysis
Thedialyzabilityoflovastatinanditsmetabolitesisunknown.

nonFDAapprovedindication

Lastrevised:October27,2015

Administration
GeneralAdministrationInformation
NOTE:Patientsreceivinglovastatintherapyshouldalsobeplacedonastandardcholesterolloweringdiet,andthisdietshouldbecontinued
throughouttherapy.Serumlipoproteinconcentrationsshouldbedeterminedperiodicallyanddosageadjustedaccordingtoindividual
responseandestablishedNCEPtreatmentguidelines.2599430125

Forstorageinformation,seethespecificproductinformationwithintheHowSuppliedsection.

RouteSpecificAdministration

OralAdministration
Avoidadministrationwithgrapefruitjuicetoavoidpotentialincreasesindrugserumconcentrations.Eveningdosingoflovastatinis
preferabletooptimizecholesterolloweringeffects.

OralSolidFormulations:
Immediatereleasetablets:Administerwiththeeveningmealtomaximizeoralbioavailability.

Extendedreleasetablets:AdministerAltoprevtabletsintheeveningatbedtime,preferablywithoutfood.Fooddecreasestheabsorption
ofAltoprev.Tabletsshouldbeswallowedwholedonotcrushorchew.

MonitoringParameters
creatinephosphokinase(CPK)

LFTs

serumcholesterolprofile

Contraindications
alcoholism

breastfeeding

children

cholestasis

contraceptionrequirements
 diabetesmellitus

electrolyteimbalance

endocrinedisease

females

geriatric

hepaticdisease

hepaticencephalopathy

hepatitis

hypotension

hypothyroidism

infants

infection

jaundice

myopathy

pregnancy

renaldisease

renalfailure

renalimpairment

rhabdomyolysis

seizuredisorder

surgery

trauma

Lovastatiniscontraindicatedinanypatientwithlovastatinhypersensitivityorhypersensitivetoanycomponentofthemedication.

Lovastatiniscontraindicatedinpatientswithactivehepaticdisease(e.g.,cholestasis,hepaticencephalopathy,hepatitis,jaundice)or
unexplainedpersistentelevationsinserumaminotransferaseconcentrations.Assessliverenzymespriortoinitiationoflovastatintherapy
andrepeatasclinicallyindicated.2860443289Afterextensivedatareview,theFDAconcludedthattheriskofseriousliverinjuryisverylow
androutineperiodicmonitoringofliverenzymeshasnotbeeneffectiveindetectionorpreventionofserioushepaticinjury.49066Patients
shouldminimizealcoholintakewhilereceivinglovastatintherapy,andlovastatinshouldbeavoidedinpatientswithalcoholism.Instruct
patientstopromptlyreportanysymptomsofhepaticinjury(e.g.,fatigue,anorexia,rightupperabdominaldiscomfort,darkurineor
jaundice).Ifserioushepaticinjurywithclinicalsymptomsand/orhyperbilirubinemiaorjaundiceoccursduringtreatmentwithlovastatin,
therapyshouldbeinterrupted.Ifanalternateetiologyisnotfound,donotrestartlovastatin.28604Priortoinitiatinglovastatintherapy,
secondarycausesforhypercholesterolemia,suchasdysproteinemias,obstructiveliverdisease,andalcoholism,shouldbeexcluded.2860443289

Allpatientsshouldbeadvisedtoreportpromptlyanyunexplainedmusclepain,tendernessorweaknessthatmayindicatemyopathy,
particularlyifaccompaniedbymalaiseorfever.Myopathysometimestakestheformofrhabdomyolysiswithorwithoutacuterenalfailure
secondarytomyoglobinuria,andrarefatalitieshaveoccurred.Discontinuelovastatinimmediatelyifmyopathyisdiagnosedorsuspected.In
mostcases,musclesymptoms,andcreatinekinase(CK)increasesresolvewhentreatmentispromptlydiscontinued.Theriskofmyopathy
and/orrhabdomyolysisisdoserelatedandmayoccurwheninitiatingtherapyorduringdoseincreases.Predisposingriskfactorsfor
myopathyincludeadvancedage,females,renaldiseaseorrenalinsufficiency,hypotension,acuteinfection,endocrinediseasesuchas
hypothyroidism,electrolyteimbalance,uncontrolledseizuredisorder,majorsurgery,andtrauma.Lovastatinmayneedtobetemporarily
withheldinpatientsexperiencingtheseconditionsacutely.TheriskofdevelopingmyopathyorrhabdomyolysisisincreasedwhenHMGCoA
reductaseinhibitorsareusedincombinationwithcertainotherdrugs.Severaldrugsareknowntodecreaselovastatinmetabolismand
increasetheriskofmyopathyandrhabdomyolysissomedrugsarecontraindicatedforusewithlovastatin.Rhabdomyolysishasbeen
associatedwithlovastatintherapyalone,whencombinedwithimmunosuppressivetherapyincludingcyclosporineintransplantpatients,and
whencombinedinnontransplantpatientswitheithergemfibrozil,lipidloweringdosesofnicotinicacid,orwiththeantifungalagent
itraconazole.Becauserenalfailureispossibleiflovastatininducedrhabdomyolysisoccurs,lovastatinmaybecontraindicatedinconditions
thatcancausedecreasedrenalperfusion.Lovastatinshouldalsobeusedwithcautioninpatientswithpreexistingrenalimpairment(renal
disease,renalfailure)anddosageadjustmentsarerecommendedinpatientswithcreatinineclearance(CrCl)lessthan30mL/minute.In
patientswithsevererenalimpairment(CrCl10to30mL/minute),theplasmaconcentrationsoftotalinhibitorsafterasingledoseof
lovastatinareapproximately2foldhigherthanthoseinhealthyvolunteers.Lovastatinshouldbediscontinuedimmediatelyinanypatient
whodevelopsmyopathyorelevationsinCPK.Theusualrecommendedstartingdoseoflovastatinextendedreleaseshouldbelimitedto20
mg/dayPOinpatientswithcomplicatedmedicalconditionsincludingrenalinsufficiencyhigherdosesshouldbeusedonlyaftercareful
considerationofthepotentialrisksandbenefits.2860443289Priortoinitiatinglovastatintherapy,secondarycausesforhypercholesterolemia,
suchasnephroticsyndromeorhypothyroidism,shouldbeexcluded.2860443289

Priortoinitiatingtherapywithlovastatin,secondarycausesforhypercholesterolemia(e.g.,uncontrolleddiabetesmellitus)shouldbe
excluded.28604Theusualstartingdoseoflovastatinextendedreleaseshouldbelimitedto20mg/dayPOinpatientswithcomplicated
medicalconditions(e.g.,diabetes)higherdosesshouldbeusedonlyaftercarefulconsiderationofthepotentialrisksandbenefits.43289If
lovastatinisinitiatedinapatientwithdiabetesmellitus,increasedmonitoringofbloodglucosecontrolmaybewarranted.IncreasedA1C,
hyperglycemia,andworseningglycemiccontrolhavebeenreportedduringtherapywithHMGCoAreductaseinhibitors.286043986649063
49066
Becausetheuseofstatinshasbeenassociatedwithsignificantbenefitforcardiovascularriskreductionandallcausemortalityat
comparableratesindiabeticandnondiabeticpatients49064,nochangestoclinicalpracticeguidelineshavebeenrecommendedineither
population.However,theincreasedriskofdiabetesmellitusshouldbeconsideredwheninitiatinglovastatintherapyinpatientsatlowriskfor
cardiovasculareventsandinpatientgroupswherethecardiovascularbenefitofstatintherapyhasnotbeenestablished.39866Althoughan
analysisofparticipantsfromtheJUPITERtrialfoundanincreasedincidenceofdevelopingdiabetesinpatientsallocatedtorosuvastatin
comparedtoplacebo(270reportsofdiabetesvs.216intheplacebogroupHR1.25,95%CI1.05to1.49,p=0.01),thecardiovascularand
mortalitybenefitsofstatintherapyexceededthediabeteshazardeveninpatientsathighriskfordevelopingdiabetes(i.e.,patientswithone
ormoremajordiabetesriskfactor:metabolicsyndrome,impairedfastingglucose,BMI30kg/m2orgreater,orA1Cover6%).Inpatientsat
highriskfordevelopingdiabetes,treatmentwithrosuvastatinwasassociatedwitha39%reductionintheprimaryendpoint(compositeof
nonfatalmyocardialinfarction,nonfatalstroke,unstableanginaorrevascularization,andcardiovasculardeath)(HR0.61,95%CI0.47to
0.79,p=0.0001),nonsignificantreductionsinvenousthromboembolism(VTE)(HR0.64,CI0.39to1.06,p=0.08)andtotalmortality(HR
83,CI0.64to1.07,p=0.15),anda28%increaseindiabetes(HR1.28,CI1.07to1.54,p=0.01).Inpatientswithnomajordiabetesrisk
factor,treatmentwithrosuvastatinwasassociatedwitha52%reductionintheprimaryendpoint(HR0.48,95%CI0.33to0.68,p=0.0001),
nonsignificantreductionsinVTE(HR0.47,CI0.21to1.03,p=0.05)andtotalmortality(HR0.78,CI0.59to1.03,p=0.08),andnoincrease
indiabetes(HR0.99,CI0.45to2.21,p=0.99).Forthoseathighriskfordevelopingdiabetes,134totalcardiovasculareventsordeathswere
avoidedforevery54newcasesofdiabetesdiagnosed.Inthosewithoutmajorriskfactors,86totalcardiovasculareventsordeathswere
avoidedwithnoexcessnewcasesofdiabetesdiagnosed.51548

Becauseadvancedage(65yearsormore)isapredisposingfactorformyopathy,includingrhabdomyolysis,lovastatinshouldbeprescribed
withcautioninthegeriatricpatient.2860443289Geriatricpatientsreceivingimmediatereleaselovastatinhavebeenreportedtohave45%
highermeanplasmalevelsofHMGCoAreductaseinhibitoryactivitycomparedtoyoungeradults.Duringclinicaltrials,nooveralldifferences
insafetyorefficacyhavebeenobservedbetweenolderandyoungerpatientsreceivinglovastatin.However,itispossiblethatsomeelderly
patientsmayhaveanincreasedcholesterolloweringresponsetolovastatin,consistentwithotherHMGCoAreductaseinhibitors.The
manufacturerforextendedreleaselovastatinrecommendsinitiatingdosageat20mg/dayforelderlypatientshigherdosesmaybe
consideredaftercarefullyweighingtherisksandbenefitsoftherapy.43289ThefederalOmnibusBudgetReconciliationAct(OBRA)regulates
medicationuseinresidentsoflongtermcarefacilities(LTCFs).AccordingtoOBRA,HMGCoAreductaseinhibitorsmayimpairliver
function,andliverfunctionmonitoringshouldoccurconsistentwithindividualmanufacturerrecommendations(e.g.,baseline,12weeksafter
initiation,afteranydoseincrease,andperiodicallythereafter).HMGCoAreductaseinhibitorsmaycausemyalgia,myopathy,and
rhabdomyolysisthatcanprecipitatekidneyfailure,particularlyincombinationwithothercholesterolloweringmedications.60742

LovastatiniscontraindicatedforuseinpregnancybecauseofthepotentialeffectsofHMGCoAreductaseinhibitorsoncholesterolpathways
andthepotentialforfetalharm.Cholesterolandotherproductsofthecholesterolbiosynthesispathwayareessentialcomponentsforfetal
development,includingsynthesisofsteroidsandcellmembranes.Treatmentshouldbeimmediatelydiscontinuedassoonaspregnancyis
recognized.Lovastatinhasbeenshowntocausemalformationsofvertebraeandribsinfetalratswhengiveninhighdoses.Inaprospective
reviewofabout100pregnanciesinwomenexposedtosimvastatinoranotherstructurallyrelatedHMGCoAreductaseinhibitor,the
incidenceofcongenitalanomalies,spontaneousabortions,andfetaldeaths/stillbirthsdidnotexceedwhatwouldbeexpectedinthegeneral
population.24910However,atherosclerosisisachronicprocessandthediscontinuationoflipidloweringdrugsduringpregnancyshouldhave
littleimpactontheoutcomeoflongtermtherapyofprimaryhypercholesterolemia.Ifthepatientbecomespregnantwhiletakingthisdrug,
lovastatinshouldbediscontinuedimmediatelyandthepatientshouldbeapprisedofthepotentialhazardtothefetus.Lovastatinshouldonly
beadministeredtofemalesofchildbearingpotential,includingadolescentsatleast1yearpostmenarche,whensuchpatientsarehighly
unlikelytoconceiveandhavebeeninformedofthepotentialhazards.Contraceptionrequirementsareadvisedfemalesshouldbecounseled
regardingappropriatemethodsofcontraceptionwhileontherapy.2860443289Theeffectsofstatinsonspermatogenesisandfertilityhavenot
beenstudiedinadequatenumbersofpatients.Theeffects,ifany,oflovastatinonthepituitarygonadalaxisinpremenopausalfemalesare
unknown.Patientstreatedwithlovastatinwhodisplayclinicalevidenceofendocrinedysfunctionshouldbeevaluatedappropriately.28604
43289

Accordingtothemanufacturer,lovastatiniscontraindicatedforuseinbreastfeedingwomen.ManyHMGCoAreductaseinhibitorsare
knowntobeexcretedintobreastmilk.Cholesterolandotherproductsofthecholesterolbiosynthesispathwayareessentialcomponentsfor
infantgrowthanddevelopment,includingsynthesisofsteroidsandcellmembranes.HMGCoAreductaseinhibitorstodecreasethesynthesis
ofcholesterolandpossiblyotherproductsofthecholesterolbiosynthesispathway.Theimportanceofcontinuedlovastatintherapytothe
mothershouldbeconsideredinmakingthedecisionwhethertodiscontinuebreastfeedingordiscontinuethemedication.2860443289If
pharmacotherapyisnecessaryinthenursingmother,anonabsorbableresinsuchascholestyramine,colesevelam,orcolestipolshouldbe
considered.Theseagentsdonotenterthebloodstreamandthuslywillnotbeexcretedduringlactation.However,resinsbindfatsoluble
vitaminsandprolongedusemayresultindeficienciesofthesevitaminsinthemotherandhernursinginfant.30812Considerthebenefitsof
breastfeeding,theriskofpotentialinfantdrugexposure,andtheriskofanuntreatedorinadequatelytreatedcondition.Ifabreastfeeding
infantexperiencesanadverseeffectrelatedtoamaternallyingesteddrug,healthcareprovidersareencouragedtoreporttheadverseeffectto
theFDA.

Safeandeffectiveuseoflovastatinhasnotbeenestablishedininfantsorchildrenlessthan10yearsofage.Dataarelackingforextended
releaselovastatininpediatricpatientsandthisproductisnotrecommendedforchildrenoradolescents.Thelongtermefficacyofstatin
therapyinchildhoodtoreducemorbidityandmortalitylaterinadulthoodhasnotbeenestablished.2860443289Becausecholesterolplaysa
crucialroleingrowthanddevelopment,theclinicalimplicationsofusingpharmacologictherapytoalterthenormalproductionofcholesterol
inyoungchildrenisnotclear.Becauseofthesepotentialsafetyconcernsandlackofsafetydata,mostexpertsgenerallyrecommenddelaying
cholesterolloweringmedicationsuntilthechildisatleast8to10yearsold.5472255759Insomecasesofseverefamilialhypercholesterolemia,
however,HMGCoAreductaseinhibitorshavebeenusedinyoungerchildrenwithcarefulmonitoringofgrowthanddevelopment.3331954722

Lastrevised:January12,2017

Interactions
Afatinib

Amiodarone

AmoxicillinClarithromycinLansoprazole

AmoxicillinClarithromycinOmeprazole

Amprenavir

Aprepitant,Fosaprepitant

Aspirin,ASAOmeprazole

Atazanavir

AtazanavirCobicistat

AzelaicAcidCopperFolicAcidNicotinamidePyridoxineZinc

Azithromycin

Barbiturates

Boceprevir

Bortezomib

Bosentan
Brigatinib

Cabozantinib

Canagliflozin

CanagliflozinMetformin

Carbamazepine

Carvedilol

Ceritinib

Cilostazol

Cimetidine

Clarithromycin

Clopidogrel

Cobicistat

CobicistatElvitegravirEmtricitabineTenofovirAlafenamide

CobicistatElvitegravirEmtricitabineTenofovirDisoproxilFumarate

Cobimetinib

Colchicine

Conivaptan

Crizotinib

Cyclosporine

Dabigatran

Daclatasvir

DalfopristinQuinupristin

Danazol

Daptomycin

Darunavir

DarunavirCobicistat

DasabuvirOmbitasvirParitaprevirRitonavir

Dasatinib

Delavirdine

Diltiazem

Doxorubicin

Dronedarone

Edoxaban

Efavirenz

EfavirenzEmtricitabineTenofovir
ElbasvirGrazoprevir

Eliglustat

EmtricitabineRilpivirineTenofovirdisoproxilfumarate

EmtricitabineTenofovirdisoproxilfumarate

Erlotinib

Erythromycin

ErythromycinSulfisoxazole

Eslicarbazepine

Esomeprazole

EsomeprazoleNaproxen

Ethanol

Etoposide,VP16

Etravirine

Everolimus

Fenofibrate

FenofibricAcid

Fluconazole

Fosamprenavir

Fosphenytoin

Gemfibrozil

grapefruitjuice

Idelalisib

Imatinib,STI571

Indinavir

Isavuconazonium

Isoniazid,INHPyrazinamide,PZARifampin

Isoniazid,INHRifampin

Isradipine

Itraconazole

Ivacaftor

Ixabepilone

Ketoconazole

Lansoprazole

LansoprazoleNaproxen

LanthanumCarbonate
LedipasvirSofosbuvir

Lomitapide

Loperamide

LoperamideSimethicone

LopinavirRitonavir

LovastatinNiacin

LumacaftorIvacaftor

LumacaftorIvacaftor

Maraviroc

MefenamicAcid

Mifepristone,RU486

Mitotane

Nefazodone

Nelfinavir

Nevirapine

Niacin,Niacinamide

NiacinSimvastatin

Nicardipine

Nilotinib

Nintedanib

Olaparib

OmbitasvirParitaprevirRitonavir

Omeprazole

OmeprazoleSodiumBicarbonate

Oritavancin

Osimertinib

Oxcarbazepine

Palbociclib

Pantoprazole

Pazopanib

Phenytoin

Posaconazole

Proteaseinhibitors

Quetiapine

Quinine
Raltegravir

Ranolazine

RedYeastRice

Ribociclib

RibociclibLetrozole

Rifabutin

Rifampin

Rifapentine

Rifaximin

Ritonavir

Rivaroxaban

Sapropterin

Saquinavir

Siltuximab

Simeprevir

SofosbuvirVelpatasvir

St.John'sWort,Hypericumperforatum

Streptogramins

Tacrolimus

Telaprevir

Telbivudine

Telithromycin

TelotristatEthyl

Temsirolimus

TenofovirAlafenamide

Tenofovir,PMPA

Teriflunomide

Ticagrelor

Tigecycline

Tipranavir

Tocilizumab

Topotecan

TrandolaprilVerapamil

Ulipristal

Vandetanib
 Vemurafenib

Venetoclax

Verapamil

Vincristine

VincristineLiposomal

Vinorelbine

Voriconazole

Warfarin

Zafirlukast

Zileuton

Zonisamide

Afatinib:Iftheconcomitantuseoflovastatinandafatinibisnecessary,considerreducingtheafatinibdoseby10mgperdayiftheoriginal
doseisnottoleratedresumethepreviousdoseofafatinibastoleratedafterdiscontinuationoflovastatin.AfatinibisaPglycoprotein(Pgp)
substrateandinhibitorinvitro,andlovastatinisaPgpinhibitorcoadministrationmayincreaseplasmaconcentrationsofafatinib.
AdministrationofanotherPgpinhibitor,ritonavir(200mgtwicedailyfor3days),1hourbeforeafatinib(singledose)increasedtheafatinib
AUCandCmaxby48%and39%,respectivelytherewasnochangeintheafatinibAUCwhenritonavirwasadministeredatthesametimeas
afatinibor6hourslater.Inhealthysubjects,therelativebioavailabilityforAUCandCmaxofafatinibwas119%and104%,respectively,when
coadministeredwithritonavir,and111%and105%whenritonavirwasadministered6hoursafterafatinib.Themanufacturerofafatinib
recommendspermanentdiscontinuationoftherapyforsevereorintolerantadversedrugreactionsatadoseof20mgperday,butdoesnot
addressaminimumdoseotherwise.2860428774344924127555331

Amiodarone:Ingeneral,inpatientstakingamiodarone,thelovastatinadultdoseshouldnotexceed40mg/dayPO.Lovastatindosesgreater
than40mg/dayshouldonlybeusedinpatientstakingamiodaroneinwhomthebenefitisexpectedtooutweightheincreasedriskof
myopathy.AmiodaronemayinhibitlovastatinmetabolismviahepaticCYP3A4isoenzymes.Monitorforsignsandsymptomsofmyopathyin
patientsreceivingamiodaroneconcurrentlywithanydoseoflovastatin.282242860455065629

AmoxicillinClarithromycinLansoprazole:Concurrentuseoflovastatinandclarithromyciniscontraindicated.Theriskofdeveloping
myopathy,rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4
inhibitorsincludingclarithromycin.Ifnoalternativetoashortcourseoftreatmentwithclarithromycinisavailable,abriefsuspensionof
lovastatintherapyduringsuchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongterm
cholesterolloweringtherapy.2823828604Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedas
substratesandinhibitorsofthePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,and
pantoprazolearealsosubstratesandinhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmay
leadtoincreasedintestinalabsorptionand/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailability
couldleadtoincreasedadverseevents,includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.For
example,Pgpinhibitionwassuspectedinacasereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causing
thirddegreeAVblock.Thepatient'smedicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),and
clarithromycin(500mgx3dosespriortoadmission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartof
esomeprazoletherapy.Duetothetimingofsymptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasma
concentrationsleadingtorhabdomyolysisandfurthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcould
haveplayedaminorroleintheinteraction,themainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarranted
whencombiningatorvastatin,lovastatin,redyeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,
omeprazole,orpantoprazole.Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,
fluvastatin,androsuvastatinmayalsodecreasetheriskofaPgpinteraction.41275412764127741278

AmoxicillinClarithromycinOmeprazole:Concurrentuseoflovastatinandclarithromyciniscontraindicated.Theriskofdeveloping
myopathy,rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4
inhibitorsincludingclarithromycin.Ifnoalternativetoashortcourseoftreatmentwithclarithromycinisavailable,abriefsuspensionof
lovastatintherapyduringsuchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongterm
cholesterolloweringtherapy.2823828604Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedas
substratesandinhibitorsofthePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,and
pantoprazolearealsosubstratesandinhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmay
leadtoincreasedintestinalabsorptionand/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailability
couldleadtoincreasedadverseevents,includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.For
example,Pgpinhibitionwassuspectedinacasereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causing
thirddegreeAVblock.Thepatient'smedicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),and
clarithromycin(500mgx3dosespriortoadmission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartof
esomeprazoletherapy.Duetothetimingofsymptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasma
concentrationsleadingtorhabdomyolysisandfurthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcould
haveplayedaminorroleintheinteraction,themainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarranted
whencombiningatorvastatin,lovastatin,redyeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,
omeprazole,orpantoprazole.Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,
fluvastatin,androsuvastatinmayalsodecreasetheriskofaPgpinteraction.41275412764127741278

Amprenavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Aprepitant,Fosaprepitant:Usecautioniflovastatinandaprepitant,fosaprepitantareusedconcurrentlyandmonitorforanincreasein
lovastatinrelatedadverseeffects,includingmyopathyandrhabdomyolysis,forseveraldaysafteradministrationofamultidayaprepitant
regimen.LovastatinisaCYP3A4substrate.Aprepitant,whenadministeredasa3dayoralregimen(125mg/80mg/80mg),isamoderate
CYP3A4inhibitorandinducerandmayincreaseplasmaconcentrationsoflovastatin.Forexample,a5dayoralaprepitantregimenincreased
theAUCofanotherCYP3A4substrate,midazolam(singledose),by2.3foldonday1andby3.3foldonday5.Aftera3dayoralaprepitant
regimen,theAUCofmidazolam(givenondays1,4,8,and15)increasedby25%onday4,andthendecreasedby19%and4%ondays8and
15,respectively.Asasingle125mgor40mgoraldose,theinhibitoryeffectofaprepitantonCYP3A4isweak,withtheAUCofmidazolam
increasedby1.5foldand1.2fold,respectively.Afteradministration,fosaprepitantisrapidlyconvertedtoaprepitantandsharesmanyofthe
samedruginteractions.However,asasingle150mgintravenousdose,fosaprepitantonlyweaklyinhibitsCYP3A4foradurationof2days
thereisnoevidenceofCYP3A4induction.Fosaprepitant150mgIVasasingledoseincreasedtheAUCofmidazolam(givenondays1and4)
byapproximately1.8foldonday1therewasnoeffectonday4.Lessthana2foldincreaseinthemidazolamAUCisnotconsideredclinically
important.28604287743067634492400274127556563

Aspirin,ASAOmeprazole:Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedassubstratesand
inhibitorsofthePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealso
substratesandinhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreased
intestinalabsorptionand/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadto
increasedadverseevents,includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgp
inhibitionwassuspectedinacasereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAV
block.Thepatient'smedicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx
3dosespriortoadmission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.
Duetothetimingofsymptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingto
rhabdomyolysisandfurthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorrolein
theinteraction,themainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombining
atorvastatin,lovastatin,redyeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,omeprazole,or
pantoprazole.Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,
androsuvastatinmayalsodecreasetheriskofaPgpinteraction.41275412764127741278

Atazanavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

AtazanavirCobicistat:Concomitantuseoflovastatinwithcobicistatiscontraindicatedduetothepotentialformyopathy,including
rhabdomyolysis.LovastatinisasubstrateforCYP3A4andthedrugtransporterPgpcobicistatisaninhibitorofbothCYP3AandPgp.
Coadministrationisexpectedtosignificantlyincreaselovastatinplasmaconcentrations.1135028604287745166458000Concurrentuseof
lovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenalfailure
issubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralproteaseinhibitors.Lovastatinisasubstrateof
CYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,coadministrationmayresultinsubstantial
increasesinplasmaconcentrationsoflovastatin.28604

AzelaicAcidCopperFolicAcidNicotinamidePyridoxineZinc:HMGCoAreductaseinhibitorshavebeenadministeredsafelywithniacin
(nicotinicacid)insomepatientshowevertheriskofpotentialmyopathyshouldbeconsidered.Rarecasesofrhabdomyolysishavebeen
reportedinpatientstakingniacin(nicotinicacid)inlipidalteringdoses(i.e.,>=1g/day)andHMGCoAreductaseinhibitors(Statins)
concurrently.Theseriousriskofmyopathyorrhabdomyolysisshouldbecarefullyweighedagainstthepotentialrisks.Patientsundergoing
combinedtherapyshouldbecarefullymonitoredformyopathyorrhabdomyolysis,particularlyintheearlymonthsoftreatmentorduring
periodsofupwarddosetitrationofeitherdrug.Chinesepatientsreceivingconcomitantlipidalteringdosesofniacincontainingproducts
shouldnotreceivethe80mgdoseofsimvastatinduetoincreasedriskofmyopathy.2798828605287292877436344Theriskofmyopathy
increaseswhenHMGCoAreductaseinhibitorsareadministeredconcurrentlywithantilipemicdosesofniacin(i.e.,1gperdayormore).
Patientsundergoingcombinedtherapyshouldbecarefullymonitoredformyopathyorrhabdomyolysis,particularlyintheearlymonthsof
treatmentorduringperiodsofupwarddosetitrationofeitherdrug.Chinesepatientsreceivingconcomitantlipidalteringdosesofniacin
containingproductsshouldnotreceivethe80mgdoseofsimvastatinduetoincreasedriskofmyopathy.Whenpossible,avoidconcurrentuse
ofHMGreductaseinhibitorswithdrugsknowntoincreasetheriskofdevelopingrhabdomyolysisoracuterenalfailure.Theseriousriskof
myopathyorrhabdomyolysisshouldbeweighedcarefullyversusthebenefitsofcombined'statin'andfibratetherapythereisnoassurance
thatperiodicmonitoringofCKwillpreventtheoccurrenceofseveremyopathyandrenaldamage.28605287292877436344

Azithromycin:BothlovastatinandazithromycinarePglycoprotein(Pgp)inhibitorsandsubstrates,socoadministrationmayleadto
increasedconcentrationsofeitheragent.Monitorpatientsforincreasedsideeffectsifthesedrugsaregiventogether.343293444841275

Barbiturates:BarbituratesaresignificanthepaticCYP3A4inducers.Monitorforpotentialreducedcholesterolloweringefficacywhen
barbituratesarecoadministeredwithHMGCoAreductaseinhibitorsmetabolizedbyCYP3A4includinglovastatin.4718

Boceprevir:Concurrentuseoflovastatinandbocepreviriscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenal
failureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithboceprevir.LovastatinisasubstrateofCYP3A4and
boceprevirisastronginhibitorofCYP3A4therefore,coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsof
lovastatin.2860444314

Bortezomib:Monitorpatientsforthedevelopmentofperipheralneuropathywhenreceivingbortezomibincombinationwithotherdrugsthat
cancauseperipheralneuropathylikeHMGCoAreductaseinhibitorstheriskofperipheralneuropathymaybeadditive.32926

Bosentan:Coadministrationofbosentanmaydecreasetheplasmaconcentrationsoflovastatin,aCYP3A4substrate.Thepossibilityof
reducedantilipemicefficacyshouldbeconsidered.PatientsreceivingCYP3A4metabolizedstatinsshouldhavecholesterollevelsmonitored
afteraddingbosentantherapytoevaluatetheneedforantilipemicdosageadjustment.47185226

Brigatinib:Monitorfordecreasedefficacyoflovastatinifcoadministrationwithbrigatinibisnecessary.LovastatinisaCYP3Asubstrateand
brigatinibinducesCYP3Ainvitroplasmaconcentrationsoflovastatinmaydecrease.28604287744127561909

Cabozantinib:Monitorforanincreaseinlovastatinrelatedadverseeventsifconcomitantusewithcabozantinibisnecessary,asplasma
concentrationsoflovastatinmaybeincreased.CabozantinibisaPglycoprotein(Pgp)inhibitorandlovastatinisasubstrateofPgpthe
clinicalrelevanceofthisfindingisunknown.28604287743449241275525065656360738

Canagliflozin:Canagliflozinisasubstrate/weakinhibitorofdrugtransporterPglycoprotein(Pgp).LovastatinisaPGPinhibitor/substrate.
Theoretically,concentrationsofeitherdrugmaybeincreased.Patientsshouldbemonitoredforchangesinglycemiccontrolandpossible
adversereactions.11350412755335539725506

CanagliflozinMetformin:Canagliflozinisasubstrate/weakinhibitorofdrugtransporterPglycoprotein(Pgp).LovastatinisaPGP
inhibitor/substrate.Theoretically,concentrationsofeitherdrugmaybeincreased.Patientsshouldbemonitoredforchangesinglycemic
controlandpossibleadversereactions.11350412755335539725506

Carbamazepine:Carbamazepine,whichisaCYP3A4inducer,maydecreasetheefficacyofHMGCoAreductaseinhibitorswhichareCYP3A4
substrates,suchaslovastatin.MonitorforpotentialreducedcholesterolloweringefficacywhenthesedrugsarecoadministeredwithHMG
CoAreductaseinhibitorswhicharemetabolizedbyCYP3A4.4718

Carvedilol:Alteredconcentrationsoflovastatinand/orcarvedilolmayoccurduringcoadministration.Carvedilolandlovastatinareboth
substratesandinhibitorsofPglycoprotein(Pgp).Usecautionifconcomitantuseisnecessaryandmonitorforincreasedsideeffects.28604
28774 34492 41275 51834 58220

Ceritinib:CeritinibisasubstrateoftheeffluxtransporterPglycoprotein(Pgp)andaninhibitorofCYP3A4lovastatinisaPgpinhibitorand
asubstrateofCYP3A4.Increasedconcentrationsofceritiniborlovastatinarepossibleifcoadministeredexercisecaution.286042877434492
41275 56563 57094

Cilostazol:Cilostazolmayinteractwithlovastatin,butitisnotcleariftheinteractioncouldbeclinicallysignificant.Inhealthyvolunteers,
peakplasmaconcentrationsoflovastatindidnotchangewithcoadministrationofcilostazol.However,peakplasmaconcentrationsandthe
AUCoflovastatin'sactivemetabolitedidincrease.Also,thepeakplasmaconcentrationsandAUCofcilostazolweredecreasedbyroughly15%
whenlovastatinwascoadministered.2651428604

Cimetidine:BecauseHMGCoAreductaseinhibitorsmaytheoreticallybluntadrenaland/orgonadalsteroidproductionbyinterferingwith
cholesterolsynthesis,themanufacturerrecommendscautionwithconcomitantadministionofdrugsthatmaydecreasetheconcentrationsor
activityofendogenoushormones,suchascimetidine.Ithasalsobeenreportedthatcimetidinecouldpotentiallyincreasetheserum
concentrationsofHMGCoAreductaseinhibitorsviatheinhibitionofthehepaticisoenzymes.Cimetidinedoesnotalterthepharmacokinetics
ofatorvastatin,cerivastatin,orpravastatin.Clinicalevidenceofpharmacokineticinteractionswithlovastatinandsimvastatinisnotavailable.
5324 5329 5334 5335 5336

Clarithromycin:Concurrentuseoflovastatinandclarithromyciniscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,and
acuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4inhibitorsincluding
clarithromycin.Ifnoalternativetoashortcourseoftreatmentwithclarithromycinisavailable,abriefsuspensionoflovastatintherapyduring
suchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterollowering
therapy.2823828604

Clopidogrel:Theoretically,clopidogrelmayinteractwithlovastatin.CYP3A4isinvolvedinthehepaticbiotransformationofclopidogreltoits
activemetabolite.Atorvastatin,aCYP3A4substrate,hasbeenreportedtoattenuatetheantiplateletactivityofclopidogrelpossiblybythe
competitiveinhibitionofCYP3A4metabolismofclopidogreltoitsactivemetabolitehowever,conflictingdataexists.Theclinicalsignificance
ofthistheoreticalinteractionisnotknown.LovastatinalsoisaCYP3A4substrateandmaytheoreticallybeinvolvedinthecompetitive
inhibitionoftheCYP3A4metabolismofclopidogrel.Patientsshouldbemonitoredforapossibledecreaseinefficacywhenclopidogrelis
administeredwithlovastatin.516353985477

Cobicistat:Concomitantuseoflovastatinwithcobicistatiscontraindicatedduetothepotentialformyopathy,includingrhabdomyolysis.
LovastatinisasubstrateforCYP3A4andthedrugtransporterPgpcobicistatisaninhibitorofbothCYP3AandPgp.Coadministrationis
expectedtosignificantlyincreaselovastatinplasmaconcentrations.1135028604287745166458000

CobicistatElvitegravirEmtricitabineTenofovirAlafenamide:Concomitantuseoflovastatinwithcobicistatiscontraindicatedduetothe
potentialformyopathy,includingrhabdomyolysis.LovastatinisasubstrateforCYP3A4andthedrugtransporterPgpcobicistatisan
inhibitorofbothCYP3AandPgp.Coadministrationisexpectedtosignificantlyincreaselovastatinplasmaconcentrations.113502860428774
51664 58000

CobicistatElvitegravirEmtricitabineTenofovirDisoproxilFumarate:Concomitantuseoflovastatinwithcobicistatiscontraindicateddueto
thepotentialformyopathy,includingrhabdomyolysis.LovastatinisasubstrateforCYP3A4andthedrugtransporterPgpcobicistatisan
inhibitorofbothCYP3AandPgp.Coadministrationisexpectedtosignificantlyincreaselovastatinplasmaconcentrations.113502860428774
5166458000Cautionisadvisedwhenadministeringtenofovir,PMPA,aPglycoprotein(Pgp)substrate,concurrentlywithinhibitorsofPgp,

suchaslovastatin.Coadministrationmayresultinincreasedabsorptionoftenofovir.Monitorfortenofovirassociatedadversereactions.28193

Cobimetinib:Ifconcurrentuseofcobimetinibandlovastatinisnecessary,usecautionandmonitorforapossibleincreaseincobimetinib
relatedadverseeffects.CobimetinibisaPglycoprotein(Pgp)substrate,andlovastatinisaPgpinhibitorcoadministrationmayresultin
increasedcobimetinibexposure.However,coadministrationofcobimetinibwithanotherPgpinhibitor,vemurafenib(960mgtwicedaily),
didnotresultinclinicallyrelevantpharmacokineticdruginteractions.2860428774344925656360281

Colchicine:Casereportsexistdescribingthedevelopmentofmyotoxicity(i.e.,musclepainandweakness,rhabdomyolysis)withthe
concurrentadministrationofcolchicineandHMGCoAreductaseinhibitors(Statins).Statinsinvolvedinthereportedcasesinclude
simvastatin,atorvastatin,fluvastatin,lovastatin,andpravastatin.Thepharmacokineticand/orpharmacodynamicmechanismofthis
interactionisnotclearhowever,bothcolchicineandstatinsareassociatedwiththedevelopmentofmyotoxicityandconcurrentusemay
increasetheriskofmyotoxicity.Patientsreceivingtheseagentsconcurrentlyshouldbemonitoredformyotoxicity.3427434275342763427734278
34279 34280 34281 34282

Conivaptan:Concomitantuseofconivaptan,apotentCYP3A4inhibitorandPglycoprotein(Pgp)inhibitor,andlovastatin,aCYP3A4/Pgp
substrate,shouldbeavoided.Conivaptan30mg/dayIVresultsina3foldincreaseintheAUCofsimvastatin,anotherCYP3A4substrate.
Theoretically,similarpharmacokineticeffectscouldbeseenwithlovastatin.Inclinicaltrialsoforalconivaptan,twocasesofrhabdomyolysis
occurredinpatientswhowerealsoreceivingHMGCoAreductaseinhibitorsknowntobemetabolizedbyCYP3A4.Accordingtothe
manufacturer,concomitantuseofconivaptanwithdrugsthatareprimarilymetabolizedbyCYP3A4,suchaslovastatin,shouldbeavoided.
SubsequenttreatmentwithCYP3Asubstrates,suchaslovastatin,maybeinitiatednosoonerthan1weekaftercompletionofconivaptan
therapy.28604287743449241275

Crizotinib:Concomitantuseofcrizotinibandlovastatinmayresultinincreasedconcentrationsofbothagents.CrizotinibisaCYP3A4andP
glycoprotein(PGP)substrate/inhibitor,whilelovastatinisaCYP3A4substrateandPGPsubstrate/inhibitor.Monitorpatientsfortoxicity,
includingmyopathyorrhabdomyolysis,withcoadministration.11350412754545853355506

Cyclosporine:Avoidtheconcurrentuseofcyclosporineandlovastatin.Cyclosporinemayincreasetheriskofmyopathy,rhabdomyolysisand
acuterenalfailureinpatientstakinglovastatin.Inuncontrolledclinicalstudiesoflovastatin,myopathywasreportedmorefrequentlyin
patientsreceivingconcomitanttherapywithcyclosporine.CyclosporinemayreducetheclearanceoftheHMGCoAreductaseinhibitors
(statins),CyclosporinehasbeenshowntoincreasetheAUCofHMGCoAreductaseinhibitors,presumablyduetoCYP3A4inhibition.28404
28604 29198

Dabigatran:Increasedserumconcentrationsofdabigatranarepossiblewhendabigatran,aPglycoprotein(Pgp)substrate,iscoadministered
withlovastatin,aPgpinhibitor.AnalternativestatinagentthatdoesnotinhibitPgpshouldbeconsidered.Considerpatientrisksversus
benenfits.Ifusetogetherismedicallynecssary,patientsshouldbemonitoredforincreasedadverseeffectsofdabigatranandanincreasedrisk
forbleeding.Inoneclinicaltrial,patientsreceivingdabigatranetexilatewithlovastatinorsimvastatinexperiencedahigherriskofmajor
hemorrhagerelativetotheuseofotherstatinsthatarenotPgpinhibitors.Whendabigatranisadministeredfortreatmentorreductionin
riskofrecurrenceofdeepvenousthrombosis(DVT)orpulmonaryembolism(PE),orprophylaxisofDVTorPEfollowinghipreplacement
surgery,avoidcoadministrationwithPgpinhibitorslikelovastatininpatientswithCrCllessthan50mL/minute.Whendabigatranisusedin
patientswithnonvalvularatrialfibrillationandsevererenalimpairment(CrCllessthan30mL/minute),avoidcoadministrationwith
lovastatin,asserumconcentrationsofdabigatranareexpectedtobehigherthanwhenadministeredtopatientswithnormalrenalfunction.P
gpinhibitionandrenalimpairmentarethemajorindependentfactorsthatresultinincreasedexposuretodabigatran.34492412754212161990

Daclatasvir:CautionandclosemonitoringisadvisedifdaclatasvirisadministeredwithHMGCoAreductaseinhibitors(Statins).Useofthese
drugstogethermayresultinelevatedStatinserumconcentrations,potentiallyresultinginadverseeffectssuchasmyopathyand
rhabdomyolysis.60001

DalfopristinQuinupristin:DalfopristinquinupristinhasbeenshowntoinhibitCYP3A4andmaydecreasetheeliminationoflovastatin,a
CYP3A4substrate.471852215335

Danazol:Theriskofmyopathyandrhabdomyolysisisincreasedifdanazolisusedwithlovastatin.Inadultpatientstakingdanazol,theinitial
lovastatindoseshouldnotexceed10mg/dayPO,andthetotallovastatindoseshouldnotexceed20mg/dayPO.Asinglecasereporthas
documentedtheonsetofmyositiswhichprogressedtorhabdomyolysiswithmyoglobinuriaafterdanazolwasaddedtoaregimencontaining
lovastatin.Althoughotherdrugswereinuseconcurrently,adruginteractionbetweendanazolandlovastatinissuspectedsincedanazol
(CYP3A4inhibitor)isknowntoinhibitlovastatinmetabolism.Ifconcurrentuseoflovastatinanddanazolisdesired,carefullyweighthe
benefitoflovastatinagainsttheriskofmyopathyandrhabdomyolysis.2860453356030

Daptomycin:DaptomycinhasbeenassociatedwithelevatedCPKinclinicaltrials.HMGCoAreductaseinhibitorsareknowntocause
myopathy.SincedataregardingcoadministrationofdaptomycinwithHMGCoAreductaseinhibitorsarelimited,temporarysuspensionof
HMGCoAreductaseinhibitortherapyshouldbeconsideredinpatientsreceivingdaptomycin.29273

Darunavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

DarunavirCobicistat:Concomitantuseoflovastatinwithcobicistatiscontraindicatedduetothepotentialformyopathy,including
rhabdomyolysis.LovastatinisasubstrateforCYP3A4andthedrugtransporterPgpcobicistatisaninhibitorofbothCYP3AandPgp.
Coadministrationisexpectedtosignificantlyincreaselovastatinplasmaconcentrations.1135028604287745166458000Concurrentuseof
lovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenalfailure
issubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralproteaseinhibitors.Lovastatinisasubstrateof
CYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,coadministrationmayresultinsubstantial
increasesinplasmaconcentrationsoflovastatin.28604

DasabuvirOmbitasvirParitaprevirRitonavir:Concomitantuseofdasabuvirombitasvirparitaprevirritonavirorombitasvirparitaprevir
ritonavirwithlovastatiniscontraindicatedduetothepotentialforsevereadversereactions,includingmyopathyandrhabdomyolysis.
Coadministrationmayresultinelevatedlovastatinsystemicconcentrations.LovastatinisasubstrateofthehepaticisoenzymeCYP3A4
ritonavirisapotentinhibitorofthisisoenzyme.Inaddition,lovastatinmayinhibitPglycoprotein(Pgp),adrugeffluxtransporterforwhich
dasabuvir,ombitasvir,paritaprevirandritonaviraresubstrates.28604287745866460002Concomitantuseofdasabuvirombitasvir
paritaprevirritonavirwithlovastatiniscontraindicatedduetothepotentialforsevereadversereactions,includingmyopathyand
rhabdomyolysis.Coadministrationmayresultinelevatedlovastatinsystemicconcentrations.Lovastatinisasubstrateofthehepatic
isoenzymeCYP3A4ritonavirisapotentinhibitorofthisisoenzyme.Inaddition,lovastatinmayinhibitPglycoprotein(Pgp),adrugefflux
transporterforwhichdasabuvir,ombitasvir,paritaprevirandritonaviraresubstrates.286042877458664Concurrentuseoflovastatinandanti
retroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenalfailureissubstantially
increasediflovastatinisadministeredconcomitantlywithantiretroviralproteaseinhibitors.LovastatinisasubstrateofCYP3A4andanti
retroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,coadministrationmayresultinsubstantialincreasesinplasma
concentrationsoflovastatin.28604

Dasatinib:Dasatinibisatimedependent,weakinhibitorofCYP3A4.Therefore,cautioniswarrantedwhendrugsthataremetabolizedbythis
enzymelikelovastatinareadministeredconcurrentlywithdasatinibasincreasedadversereactionsmayoccur.47189211

Delavirdine:Theriskofmyopathy,includingrhabdomyolysis,maybeincreasedwhendelavirdineisgivenincombinationwithHMGCoA
reductaseinhibitors.ConcomitantuseofdelavirdineandtheCYP3A4substratelovastatinisnotrecommended.IftreatmentwithanHMG
CoAreductaseinhibitorisnecessary,pravastatinshouldalsobeconsidered,sinceitisnotsignificantlymetabolizedbyCYP3A4orCYP2C9
isoenzymes.466385206

Diltiazem:Coadministrationofdiltiazemandlovastatinincreasestheriskformyopathy/rhabdomyolysisparticularlywithhigherdosesof
lovastatin.Inadultpatientstakingdiltiazem,theinitiallovastatindoseshouldnotexceed10mg/dayPO,andthetotallovastatindoseshould
notexceed20mg/dayPO.Thebenefitsoftheuseoflovastatininpatientstakingdiltiazemshouldbecarefullyweighedagainsttherisksof
thiscombination.2860476

Doxorubicin:LovastatinisaPglycoprotein(Pgp)inhibitoranddoxorubicinisamajorPgpsubstrate.Clinicallysignificantinteractionshave
beenreportedwhendoxorubicinwascoadministeredwithinhibitorsofPgp,resultinginincreasedconcentrationandclinicaleffectof
doxorubicin.Avoidcoadministrationoflovastatinanddoxorubicinifpossible.Ifnotpossible,closelymonitorforincreasedsideeffectsof
doxorubicinincludingmyelosuppressionandcardiotoxicity.28604287743449256361

Dronedarone:DronedaroneismetabolizedbyCYP3AandisaninhibitorofCYP3A,CYP2D6,andPgp.LovastatinisasubstrateforCYP3A4.
Coadministrationofdronedaroneandsimvastatin,asubstrateforCYP2D6andCYP3A4,resultedinanincreaseinsimvastatinand
simvastatinacidexposureby4and2fold,respectively.Monitorforsignsandsymptomsofmyopathyinpatientsreceivingdronedarone
concurrentlywithlovastatin.36101

Edoxaban:Coadministrationofedoxabanandlovastatinmayresultinincreasedconcentrationsofedoxaban.EdoxabanisaPglycoprotein
(Pgp)substrateandlovastatinisaPgpinhibitor.Increasedconcentrationsofedoxabanmayoccurduringconcomitantuseoflovastatin
monitorforincreasedadverseeffectsofedoxaban.Dosagereductionmaybeconsideredforpatientsbeingtreatedfordeepvenousthrombosis
(DVT)orpulmonaryembolism.4722758685

Efavirenz:EfavirenzhaspotentialtoinduceCYP3A4isoenzymeswhichmaydecreasetheefficacyoflovastatin.47185172

EfavirenzEmtricitabineTenofovir:Cautionisadvisedwhenadministeringtenofovir,PMPA,aPglycoprotein(Pgp)substrate,concurrently
withinhibitorsofPgp,suchaslovastatin.Coadministrationmayresultinincreasedabsorptionoftenofovir.Monitorfortenofovirassociated
adversereactions.28193EfavirenzhaspotentialtoinduceCYP3A4isoenzymeswhichmaydecreasetheefficacyoflovastatin.47185172

ElbasvirGrazoprevir:Themanufacturerofelbasvirgrazoprevirrecommendscautionduringconcurrentadministrationwithlovastatin.
Althoughthisinteractionhasnotbeenstudied,useofthesedrugstogethermayresultinelevatedlovastatinplasmaconcentrations.Usethe
lowesteffectivelovastatindoseandmonitorpatientsforstatinrelatedadverseevents(suchasmyopathy).Lovastatinisasubstrateforthe
hepaticenzymesCYP3AgrazoprevirisaweakCYP3Ainhibitor.2860460523

Eliglustat:Coadministrationoflovastatinandeliglustatmayresultinincreasedplasmaconcentrationsoflovastatin.Monitorpatientsclosely
forlovastatinrelatedadverseeffectsincludingmyalgia,myopathy,myasthenia,and/orrhabdomyolysisifappropriate,considerreducingthe
lovastatindosageandtitratingtoclinicaleffect.LovastatinisaPglycoprotein(Pgp)substrateeliglustatisaPgpinhibitor.287743449241275
57803

EmtricitabineRilpivirineTenofovirdisoproxilfumarate:Cautionisadvisedwhenadministeringtenofovir,PMPA,aPglycoprotein(Pgp)
substrate,concurrentlywithinhibitorsofPgp,suchaslovastatin.Coadministrationmayresultinincreasedabsorptionoftenofovir.Monitor
fortenofovirassociatedadversereactions.28193

EmtricitabineTenofovirdisoproxilfumarate:Cautionisadvisedwhenadministeringtenofovir,PMPA,aPglycoprotein(Pgp)substrate,
concurrentlywithinhibitorsofPgp,suchaslovastatin.Coadministrationmayresultinincreasedabsorptionoftenofovir.Monitorfor
tenofovirassociatedadversereactions.28193

Erlotinib:ConcomitantuseoferlotinibandHMGcoAreductaseinhibitors(statins)mayincreasetheriskforstatininducedmyopathy.
Myopathyandrhabdomyolysishasbeenobservedrarelywithconcurrentuseofstatinsanderlotinibduringpostmarketuse.Themechanism
forthisinteractionisnotknown.Useerlotinibandstatinstogetherwithcautionandmonitorforsignsorsymptomsofstatinrelatedadverse
eventsincludingmyopathy(e.g.,musclepainorweakness)andrhabdomyolysis(e.g.,nausea/vomiting,darkcoloredurine).54670

Erythromycin:Concurrentuseoflovastatinanderythromyciniscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,and
acuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4inhibitorsincluding
erythromycin.Ifnoalternativetoashortcourseoftreatmentwitherythromycinisavailable,abriefsuspensionoflovastatintherapyduring
suchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterollowering
therapy.28604

ErythromycinSulfisoxazole:Concurrentuseoflovastatinanderythromyciniscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4inhibitors
includingerythromycin.Ifnoalternativetoashortcourseoftreatmentwitherythromycinisavailable,abriefsuspensionoflovastatin
therapyduringsuchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterol
loweringtherapy.28604

Eslicarbazepine:InvivostudiessuggesteslicarbazepineisaninducerofCYP3A4.CoadministrationofCYP3A4substrates,suchaslovastatin,
mayresultindecreasedserumconcentrationsofthesubstrate.Monitorfordecreasedefficacyoflovastatinifcoadministeredwith
eslicarbazepine.Adjustthedoseoflovastatinifclinicallysignificantalterationsinserumlipdsarenoted.2860456436

Esomeprazole:LovastatinisaHMGCoAreductaseinhibitor(statin)recognizedasasubstrateandinhibitorofthePglycoprotein(Pgp)
transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealsosubstratesandinhibitorsofPgp.Dueto
competitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreasedintestinalabsorptionand/ordecreasedhepatic
excretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadtoincreasedadverseevents,includingseriousmyopathies
inthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgpinhibitionwassuspectedinacasereportinvolvinga
patientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAVblock.Thepatient'smedicationhistoryincluded
atorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx3dosespriortoadmission).Symptomsof
weakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.Duetothetimingofsymptomonset,
clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingtorhabdomyolysisandfurther
complications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorroleintheinteraction,themain
pathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombininglovastatinwithesomeprazole.
Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,androsuvastatin
mayalsodecreasetheriskofaPgpinteraction.41275412764127741278

EsomeprazoleNaproxen:LovastatinisaHMGCoAreductaseinhibitor(statin)recognizedasasubstrateandinhibitorofthePglycoprotein
(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealsosubstratesandinhibitorsofPgp.
DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreasedintestinalabsorptionand/ordecreased
hepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadtoincreasedadverseevents,includingserious
myopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgpinhibitionwassuspectedinacasereport
involvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAVblock.Thepatient'smedicationhistory
includedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx3dosespriortoadmission).Symptoms
ofweakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.Duetothetimingofsymptomonset,
clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingtorhabdomyolysisandfurther
complications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorroleintheinteraction,themain
pathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombininglovastatinwithesomeprazole.
Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,androsuvastatin
mayalsodecreasetheriskofaPgpinteraction.41275412764127741278

Ethanol:Intakeofethanolshouldbeavoidedorminimizedduringlovastatintherapytoreducetheriskofhepaticinjury.Themanufacturer
advisescautionforuseoflovastatininpatientswhoingestsubstantialquantitiesofalcohol.5335

Etoposide,VP16:Monitorforanincreasedincidenceofetoposiderelatedadverseeffectsifusedconcomitantlywithlovastatin.Lovastatinis
aninhibitorofPglycoprotein(Pgp)andetoposide,VP16isaPgpsubstrate.Coadministrationmayincreaseetoposideconcentrations.28604
28774 34492 34509 41275 56563 57989

Etravirine:Theriskofmyopathy,includingrhabdomyolysis,maybeincreasedwhenantiretroviralsaregivenincombinationwithHMGCoA
reductaseinhibitors.Concomitantuseofetravirineandlovastatin(CYP3A4substrate)mayresultinlowerplasmaconcentrationsofthe
HMGCoAreductaseinhibitordoseadjustmentsmaybenecessary.33718

Everolimus:Immunosuppressantssuchaseverolimus,especiallywhenusedalongwithcyclosporine,canproducenephrotoxicitywith
decreasesincreatinineclearanceandrisesinserumcreatinine.Deteriorationofrenalfunctionincreasestheriskformyopathyand
rhabomyolysiswithlipidloweringtherapysuchastheHMGCoAreductaseinhibitors(statins).Carefullymonitorforrenalfunction
deteriorationandsymptomsofmyopathy.Becauseoftheinteractionofstatinswithcyclosporine,clinicaltrialsofeverolimusand
cyclosporineinkidneytransplantpatientsstronglydiscouragedpatientsfromreceivingeithersimvastatinorlovastatin.Population
pharmacokineticanalysesdetectednoinfluenceofsimvastatin,aCYP3A4substrate,ontheclearanceofeverolimus.Singledose
administrationofeverolimuswitheitheratorvastatinorpravastatintohealthysubjectsdidnotinfluencethepharmacokineticsof
atorvastatin,pravastatin,oreverolimustoaclinicallyrelevantextenthowever,theseresultscannotbeextrapolatedtootherHMGCoA
reductaseinhibitors.Creatinephosphokinase(CPK)levelsshouldbeassessedinpatientsreportingsymptomsofmuscletoxicity,andthe
statinshouldbediscontinuedifmarkedlyelevatedCPKlevelsoccurormyopathyormyositisissuspectedordiagnosed.351444490349952

Fenofibrate:Concurrentuseoffenofibrateandlovastatinmayincreasetheriskofmyopathy,rhabdomyolysis,andacuterenalfailure.The
seriousriskofmyopathyandrhabdomyolysisshouldbeweighedcarefullyagainstthebenefitoffurtheralterationinlipidconcentrationsby
thecombineduseoffenofibrateorfenofibricacidandlovastatin.286046131

FenofibricAcid:Concurrentuseoffenofibricacidandlovastatinmayincreasetheriskofmyopathy,rhabdomyolysis,andacuterenalfailure.
Theseriousriskofmyopathyandrhabdomyolysisshouldbeweighedcarefullyagainstthebenefitoffurtheralterationinlipidconcentrations
bythecombineduseoffenofibricacidandlovastatin.2860449952

Fluconazole:Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenalfailuremaybeincreasediflovastatinisadministered
concomitantlywithfluconazole.LovastatinisasensativeCYP3A4substrate.FluconazolealsoinhibitsCYP3A4isoenzymes,buttoalesser
extentthanketoconazoleanditraconazole.28604344475771

Fosamprenavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Fosphenytoin:Fosphenytoin,aCYP3A4inducer,maydecreasetheefficacyoflovastatin,aCYP3A4substrate.Onecasestudydocumentedan
increaseintotalserumcholesterolconcentrationswhenphenytoin,theactivemetaboliteoffosphenytoin,wasadministeredconcurrentlywith
anotherHMGCoAreductaseinhibitor,atorvastatin.Totalserumcholesterolconcentrationsthendecreasedwhenphenytoinwas
discontinued.Monitorforpotentialreducedcholesterolloweringefficacy.280012853528774

Gemfibrozil:Avoidtheconcurrentuseofgemfibrozilandlovastatin.Gemfibrozilmayincreasetheriskofmyopathy,rhabdomyolysisand
acuterenalfailureinpatientstakinglovastatin.Inuncontrolledclinicalstudiesoflovastatin,myopathywasreportedmorefrequentlyin
patientsreceivingconcomitanttherapywithgemfibrozil.Preliminarydatasuggeststhattheadditionofgemfibroziltolovastatintherapydoes
notresultingreaterreductionsinLDLCthanthatachievedwithlovastatinalone.2824828604

Grapefruitjuice:Largequantitiesofgrapefruitjuice(>1quartdaily)shouldbeavoidedduringlovastatintherapyduetotheincreasedriskof
myopathy.GrapefruitjuicecontainscompoundsthatinhibittheCYP3A4isozymeinthegutwall.Coadministrationwithgrapefruitjuice
increasestheplasmaconcentrationsandAUCoflovastatin(anditsbetahydroxyacidmetabolite)andmayhaveasimilareffectontheserum
concentrationsofsimvastatin,atorvastatin,andcerivastatin,whichareCYP3A4substrates.Grapefruitjuiceshouldbeavoidedorminimized
inpatientstakingtheseagentstoavoidthepotentialfordrugaccumulationandtoxicity(ie.myopathyandrhabdomyolysis).28604

Idelalisib:Avoidconcomitantuseofidelalisib,astrongCYP3Ainhibitor,withlovastatin,aCYP3Asubstrate,aslovastatintoxicities,suchas
myopathy,maybesignificantlyincreased.TheAUCofasensitiveCYP3Asubstratewasincreased5.4foldwhencoadministeredwith
idelalisib.Consideranalternativetolovastatin.Asingledoseof10mgofrosuvastatinwasadministeredaloneandafteridelailsib150mgfor
12dosesinhealthysubjectsandnochangesinexposuretorosuvastatinwereobserved.533557675

Imatinib,STI571:Imatinib,STI571isapotentinhibitorofthecytochromeP4503A4isoenzyme.Concurrentuseoflovastatinandimatinib
mayresultinincreasedlevelsoflovastatinandpotentialtoxicity.Concurrentuseofsimvastatinandimatinibresultedin2and3.5fold
increasesinsimvastatinCmaxandAUCvalues,respectively.47184966

Indinavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Isavuconazonium:Concomitantuseofisavuconazoniumwithlovastatinmayresultinincreasedserumconcentrationsoflovastatin.
LovastatinisasubstrateofthehepaticisoenzymeCYP3A4anddrugtransporterPglycoprotein(Pgp)isavuconazole,theactivemoietyof
isavuconazonium,isaninhibitorofCYP3A4andPgp.Cautionandclosemonitoringareadvisedifthesedrugsareusedtogether.2860428774
34492 41275 56563 59042

Isoniazid,INHPyrazinamide,PZARifampin:Rifampinhasbeenreportedtosignificantlyincreasetheplasmaclearanceanddecreasethe
serumconcentrationsofatorvastatin,simvastatinandfluvastatin,withthepotentialforreducedantilipemicefficacy.Althoughnotstudied,a
similarinteractioncanbeexpectedbetweenotherrifamycins(e.g.,rifabutin,rifapentine)andotherHMGCoAreductaseinhibitors(Statins).
Toevaluatethisinteraction,monitorserumlipidconcentrationsduringcoadministrationofrifamycinswithHMGCoAreductaseinhibitors.
29447 32067

Isoniazid,INHRifampin:Rifampinhasbeenreportedtosignificantlyincreasetheplasmaclearanceanddecreasetheserumconcentrations
ofatorvastatin,simvastatinandfluvastatin,withthepotentialforreducedantilipemicefficacy.Althoughnotstudied,asimilarinteractioncan
beexpectedbetweenotherrifamycins(e.g.,rifabutin,rifapentine)andotherHMGCoAreductaseinhibitors(Statins).Toevaluatethis
interaction,monitorserumlipidconcentrationsduringcoadministrationofrifamycinswithHMGCoAreductaseinhibitors.2944732067

Isradipine:Isradipinehasbeenshowntoincreasetheclearanceoflovastatin.Lovastatinserumconcentrationswerecorrespondinglylower
duringisradipineadministration.Lovastatindidnothaveanyeffectonisradipinepharmacokinetics.Theclinicalsignificanceofthisdrug
interactionisunclearatthistime.5866

Itraconazole:Concurrentuseanduseoflovastatinforupto2weeksafterdiscontinuationofitraconazoletreatmentiscontraindicated.Ina
small,doubleblindstudyinhealthyvolunteers,lovastatinmeanpeakconcentrationsandlovastatinAUCincreasedbymorethan20fold
whensubjectswerepretreatedwithitraconazole.Althoughsideeffectswerenotreported,onepatientexperienceda10foldincreasein
creatinekinase.Oneothercaseisnotedofapatientwhodevelopedrhabdomyolysiswhenitraconazolewasaddedtoastableregimenof
lovastatinandniacin.BecausepravastatindoesnotsignificantlyrelyontheCYP3A4isoenzymeformetabolism,itislesslikelytoexhibitan
interactionwiththeazoleantifungals.Comparedtoa19to20foldincreaseinlovastatinAUCwithconcurrentitraconazole,theAUCof
pravastatinisincreased1.7foldwhencoadministeredwithitraconazole.TherelativelysmallincreaseinpravastatinAUCduringitraconazole
therapyispostulatedbythemanufacturertobeduetoinhibitionofPglycoproteintransport.2860440233579057915793929

Ivacaftor:Usecautionwhenadministeringivacaftorandlovastatinconcurrently.IvacaftorisaninhibitorofCYP3AandPglycoprotein(Pgp).
CoadministrationofivacaftorwithCYP3AandPgpsubstrates,suchaslovastatin,canincreaselovastatinexposureleadingtoincreasedor
prolongedtherapeuticeffectsandadverseevents.286044127548524

Ixabepilone:IxabepiloneisaweakinhibitorofPglycoprotein(Pgp).LovastatinisaPgpsubstrate,andconcomitantuseofixabepilonewitha
Pgpsubstratemaycauseanincreaseinlovastatinconcentrations.UsecautionifixabepiloneiscoadministeredwithaPgpsubstrate.10415

Ketoconazole:Concurrentuseoflovastatinandketoconazoleiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacute
renalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4inhibitorsincludingketoconazole.Ifno
alternativetoashortcourseoftreatmentwithketoconazoleisavailable,abriefsuspensionoflovastatintherapyduringsuchtreatmentcanbe
consideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterolloweringtherapy.28604

Lansoprazole:Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedassubstratesandinhibitorsof
thePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealsosubstratesand
inhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreasedintestinalabsorption
and/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadtoincreasedadverseevents,
includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgpinhibitionwassuspectedina
casereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAVblock.Thepatient's
medicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx3dosespriorto
admission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.Duetothetimingof
symptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingtorhabdomyolysisand
furthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorroleintheinteraction,the
mainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombiningatorvastatin,lovastatin,red
yeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,omeprazole,orpantoprazole.Substitutingwith
dexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,androsuvastatinmayalsodecrease
theriskofaPgpinteraction.41275412764127741278

LansoprazoleNaproxen:Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedassubstratesand
inhibitorsofthePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealso
substratesandinhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreased
intestinalabsorptionand/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadto
increasedadverseevents,includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgp
inhibitionwassuspectedinacasereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAV
block.Thepatient'smedicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx
3dosespriortoadmission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.
Duetothetimingofsymptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingto
rhabdomyolysisandfurthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorrolein
theinteraction,themainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombining
atorvastatin,lovastatin,redyeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,omeprazole,or
pantoprazole.Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,
androsuvastatinmayalsodecreasetheriskofaPgpinteraction.41275412764127741278

LanthanumCarbonate:Oralcompoundsknowntointeractwithantacids,likeHMGCoAreductaseinhibitors,shouldnotbetakenwithin2
hoursofdosingwithlanthanumcarbonate.Iftheseagentsareusedconcomitantly,spacethedosingintervalsappropriately.Monitorserum
concentrationsandclinicalcondition.32306

LedipasvirSofosbuvir:Cautionandclosemonitoringofadversereactions,suchasmyopathyandrhabdomyolysis,isadvisedwith
concomitantadministrationoflovastatinandledipasvirsofosbuvir.Bothledipasvirandlovastatinaresubstratesandinhibitorsofthedrug
transporterPglycoprotein(Pgp)sofosbuvirisaPgpsubstrate.Takingthesedrugstogethermayincreaseplasmaconcentrationsofallthree
drugs.Accordingtothemanufacturer,nodosageadjustmentsarerequiredwhenledipasvirsofosbuvirisadministeredconcurrentlywithP
gpinhibitors.2860428774344924127558167

Lomitapide:Theriskofdevelopingmyopathy,includingrhabdomyolysismaybeincreasediflovastatinisadministeredconcomitantlywith
lomitapide.Considerreducingthedoseoflovastatinwheninitiatinglomitapide.Althoughtheinteractionbetweenlovastatinandlomitapide
hasnotbeenstudied,coadministrationoflomitapideandsimvastatinapproximatelydoublestheexposuretosimvastatin.Becausethe
metabolizingenzymesandtransportersresponsibleforthedispositionoflovastatinandsimvastatinaresimilar,increasedexposureto
lovastatinshouldalsobeexpected.52698

Loperamide:Theplasmaconcentrationofloperamide,aPglycoprotein(Pgp)substrate,maybeincreasedwhenadministeredconcurrently
withlovastatin,aPgpinhibitor.Ifthesedrugsareusedtogether,monitorforloperamideassociatedadversereactions,suchasCNSeffects
andcardiactoxicities(i.e.,syncope,ventriculartachycardia,QTprolongation,torsadedepointes,cardiacarrest).2860428774301063449241275
56563 60864

LoperamideSimethicone:Theplasmaconcentrationofloperamide,aPglycoprotein(Pgp)substrate,maybeincreasedwhenadministered
concurrentlywithlovastatin,aPgpinhibitor.Ifthesedrugsareusedtogether,monitorforloperamideassociatedadversereactions,suchas
CNSeffectsandcardiactoxicities(i.e.,syncope,ventriculartachycardia,QTprolongation,torsadedepointes,cardiacarrest).286042877430106
34492 41275 56563 60864

LopinavirRitonavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

LovastatinNiacin:TheriskofmyopathyincreaseswhenHMGCoAreductaseinhibitorsareadministeredconcurrentlywithantilipemic
dosesofniacin(i.e.,1gperdayormore).Patientsundergoingcombinedtherapyshouldbecarefullymonitoredformyopathyor
rhabdomyolysis,particularlyintheearlymonthsoftreatmentorduringperiodsofupwarddosetitrationofeitherdrug.Chinesepatients
receivingconcomitantlipidalteringdosesofniacincontainingproductsshouldnotreceivethe80mgdoseofsimvastatinduetoincreased
riskofmyopathy.Whenpossible,avoidconcurrentuseofHMGreductaseinhibitorswithdrugsknowntoincreasetheriskofdeveloping
rhabdomyolysisoracuterenalfailure.Theseriousriskofmyopathyorrhabdomyolysisshouldbeweighedcarefullyversusthebenefitsof
combined'statin'andfibratetherapythereisnoassurancethatperiodicmonitoringofCKwillpreventtheoccurrenceofseveremyopathy
andrenaldamage.28605287292877436344

LumacaftorIvacaftor:Lumacaftorivacaftormayalterthesystemicexposureoflovastatinifusedtogether,monitorserumlipid
concentrations.LovastatinisasubstrateofCYP3A4andthePglycoprotein(Pgp)drugtransporter.LumacaftorisastrongCYP3Ainducerin
vitrodatasuggestslumacaftorivacaftormayalsoinduceand/orinhibitPgp.WhiletheinductionoflovastatinthroughtheCYP3Apathway
mayleadtodecreasedplasmaconcentrationsoflovastatin,theneteffectoflumacaftorivacaftoronPgptransportisnotclear.2860428774
59891

LumacaftorIvacaftor:Usecautionwhenadministeringivacaftorandlovastatinconcurrently.IvacaftorisaninhibitorofCYP3AandP
glycoprotein(Pgp).CoadministrationofivacaftorwithCYP3AandPgpsubstrates,suchaslovastatin,canincreaselovastatinexposure
leadingtoincreasedorprolongedtherapeuticeffectsandadverseevents.286044127548524

Maraviroc:Usecautionandcloselymonitorforincreasedadverseeffectswiththecoadministrationofmaravirocandlovastatinasincreased
maravirocconcentrationsmayoccur.MaravirocisasubstrateofPglycoprotein(Pgp)lovastatinisaninhibitorofPgp.TheeffectsofPgp
ontheconcentrationsofmaravirocareunknown,althoughanincreaseinconcentrationsandthus,toxicity,arepossible.286042877433473

MefenamicAcid:MefenamicacidisasubstrateforCYP2C9.Inhibitorsofthisenzyme,suchaslovastatin,mayleadtoincreasedserum
concentrationsofmefenamicacid.Ifthesedrugsareadministeredconcurrently,monitorforNSAIDrelatedsideeffects,suchasfluid
retentionorGIirritation,orrenaldysfunctionandadjustthemefenamicaciddose,ifneeded.30570

Mifepristone,RU486:WhenusedinthetreatmentofCushing'ssyndrome,coadministrationofmifepristonewithlovastatinis
contraindicatedbasedonstudiesdemonstratingsignificantdrugexposureincreaseswhichmayleadtoanincreasedriskofmyopathyand
rhabdomyolysis.Mifepristone,RU486inhibitsCYP3A4invitro.Coadministrationofmifepristonemayleadtoanincreaseinserumlevels
drugsmetabolizedviaCYP3A4,suchaslovastatin.Duetothesloweliminationofmifepristonefromthebody,suchinteractionsmaybe
observedforaprolongedperiodaftermifepristoneadministration.4718472048697

Mitotane:Usecautionifmitotaneandlovastatinareusedconcomitantly,andmonitorfordecreasedefficacyoflovastatinandapossible
changeindosagerequirements.MitotaneisastrongCYP3A4inducerandlovastatinisaCYP3A4substratecoadministrationmayresultin
decreasedplasmaconcentrationsoflovastatin.286042877434492412754193456563

Nefazodone:Concurrentuseoflovastatinandnefazodoneiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacute
renalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithnefazodone.LovastatinisasubstrateofCYP3A4and
nefazodoneisastronginhibitorofCYP3A4therefore,coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsof
lovastatin.28604

Nelfinavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Nevirapine:Nevirapine,whichisaCYP3A4inducer,maydecreasetheefficacyofHMGCoAreductaseinhibitorswhichareCYP3A4
substratesincludinglovastatin.MonitorforpotentialreducedcholesterolloweringefficacywhenthesedrugsarecoadministeredwithHMG
CoAreductaseinhibitorswhicharemetabolizedbyCYP3A447185506

Niacin,Niacinamide:TheriskofmyopathyincreaseswhenHMGCoAreductaseinhibitorsareadministeredconcurrentlywithantilipemic
dosesofniacin(i.e.,1gperdayormore).Patientsundergoingcombinedtherapyshouldbecarefullymonitoredformyopathyor
rhabdomyolysis,particularlyintheearlymonthsoftreatmentorduringperiodsofupwarddosetitrationofeitherdrug.Chinesepatients
receivingconcomitantlipidalteringdosesofniacincontainingproductsshouldnotreceivethe80mgdoseofsimvastatinduetoincreased
riskofmyopathy.Whenpossible,avoidconcurrentuseofHMGreductaseinhibitorswithdrugsknowntoincreasetheriskofdeveloping
rhabdomyolysisoracuterenalfailure.Theseriousriskofmyopathyorrhabdomyolysisshouldbeweighedcarefullyversusthebenefitsof
combined'statin'andfibratetherapythereisnoassurancethatperiodicmonitoringofCKwillpreventtheoccurrenceofseveremyopathy
andrenaldamage.28605287292877436344

NiacinSimvastatin:TheriskofmyopathyincreaseswhenHMGCoAreductaseinhibitorsareadministeredconcurrentlywithantilipemic
dosesofniacin(i.e.,1gperdayormore).Patientsundergoingcombinedtherapyshouldbecarefullymonitoredformyopathyor
rhabdomyolysis,particularlyintheearlymonthsoftreatmentorduringperiodsofupwarddosetitrationofeitherdrug.Chinesepatients
receivingconcomitantlipidalteringdosesofniacincontainingproductsshouldnotreceivethe80mgdoseofsimvastatinduetoincreased
riskofmyopathy.Whenpossible,avoidconcurrentuseofHMGreductaseinhibitorswithdrugsknowntoincreasetheriskofdeveloping
rhabdomyolysisoracuterenalfailure.Theseriousriskofmyopathyorrhabdomyolysisshouldbeweighedcarefullyversusthebenefitsof
combined'statin'andfibratetherapythereisnoassurancethatperiodicmonitoringofCKwillpreventtheoccurrenceofseveremyopathy
andrenaldamage.28605287292877436344

Nicardipine:NicardipineisaninhibitorofCYP3A4isoenzymes.Coadministrationwithnicardipinemayleadtoanincreaseinserumlevelsof
drugsthatareCYP3A4substratesincludinglovastatin.4718

Nilotinib:Concomitantuseofnilotinib,aCYP3A4andPglycoprotein(Pgp)inhibitor,andlovastatin,aCYP3A4andPgpsubstrate,may
resultinincreasedlovastatinlevels.Anlovastatindosereductionmaybenecessaryifthesedrugsareusedtogether.Bealertforsymptomsof
statininducedmyopathy.2800133557

Nintedanib:LovastatinisamoderateinhibitorofPglycoprotein(Pgp)andnintedanibisaPgpsubstrate.Coadministrationmayincrease
theconcentrationandclinicaleffectofnintedanib.Ifconcomitantuseoflovastatinandnintedanibisnecessary,closelymonitorforincreased
nintedanibsideeffectsincludinggastrointestinaltoxicity,elevatedliverenzymes,andhypertension.Adosereduction,interruptionoftherapy,
ordiscontinuationoftherapymaybenecessary.286042877434492412755656358203

Olaparib:Usecautionifcoadministrationofolaparibwithlovastatinisnecessary,duetoanincreasedriskoflovastatinandolaparibrelated
adversereactions.LovastatinisaPglycoprotein(Pgp)substrate/inhibitor.OlaparibisalsoaninvitroPgpsubstrate/inhibitor,although
theclinicalrelevanceisunknown.286042877434492412755656358662

OmbitasvirParitaprevirRitonavir:Concomitantuseofdasabuvirombitasvirparitaprevirritonavirorombitasvirparitaprevirritonavir
withlovastatiniscontraindicatedduetothepotentialforsevereadversereactions,includingmyopathyandrhabdomyolysis.
Coadministrationmayresultinelevatedlovastatinsystemicconcentrations.LovastatinisasubstrateofthehepaticisoenzymeCYP3A4
ritonavirisapotentinhibitorofthisisoenzyme.Inaddition,lovastatinmayinhibitPglycoprotein(Pgp),adrugeffluxtransporterforwhich
dasabuvir,ombitasvir,paritaprevirandritonaviraresubstrates.28604287745866460002Concurrentuseoflovastatinandantiretroviral
proteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenalfailureissubstantiallyincreasedif
lovastatinisadministeredconcomitantlywithantiretroviralproteaseinhibitors.LovastatinisasubstrateofCYP3A4andantiretroviral
proteaseinhibitorsarestronginhibitorsofCYP3A4therefore,coadministrationmayresultinsubstantialincreasesinplasmaconcentrations
oflovastatin.28604

Omeprazole:Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedassubstratesandinhibitorsof
thePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealsosubstratesand
inhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreasedintestinalabsorption
and/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadtoincreasedadverseevents,
includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgpinhibitionwassuspectedina
casereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAVblock.Thepatient's
medicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx3dosespriorto
admission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.Duetothetimingof
symptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingtorhabdomyolysisand
furthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorroleintheinteraction,the
mainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombiningatorvastatin,lovastatin,red
yeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,omeprazole,orpantoprazole.Substitutingwith
dexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,androsuvastatinmayalsodecrease
theriskofaPgpinteraction.41275412764127741278

OmeprazoleSodiumBicarbonate:Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedas
substratesandinhibitorsofthePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,and
pantoprazolearealsosubstratesandinhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmay
leadtoincreasedintestinalabsorptionand/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailability
couldleadtoincreasedadverseevents,includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.For
example,Pgpinhibitionwassuspectedinacasereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causing
thirddegreeAVblock.Thepatient'smedicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),and
clarithromycin(500mgx3dosespriortoadmission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartof
esomeprazoletherapy.Duetothetimingofsymptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasma
concentrationsleadingtorhabdomyolysisandfurthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcould
haveplayedaminorroleintheinteraction,themainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarranted
whencombiningatorvastatin,lovastatin,redyeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,
omeprazole,orpantoprazole.Substitutingwithdexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,
fluvastatin,androsuvastatinmayalsodecreasetheriskofaPgpinteraction.41275412764127741278

Oritavancin:LovastatinismetabolizedbyCYP3A4oritavancinisaweakCYP3A4inducer.Plasmaconcentrationsandefficacyoflovastatin
maybereducedifthesedrugsareadministeredconcurrently.287744328957741

Osimertinib:Usecautionifcoadministrationofosimertinibandlovastatinisnecessary,duetotheriskofincreasedosimertinibexposure.
LovastatinisaPglycoprotein(Pgp)inhibitorandosimertinibisaninvitroPgpsubstrate.Coadministrationmayincreaseosimertinib
relatedadversereactions.286042877434492412755656360297

Oxcarbazepine:Oxcarbazepine,whichisaCYP3A4inducer,maydecreasetheefficacyofHMGCoAreductaseinhibitorswhichareCYP3A4
substratesincludinglovastatin.MonitorforpotentialreducedcholesterolloweringefficacywhenthesedrugsarecoadministeredwithHMG
CoAreductaseinhibitorswhicharemetabolizedbyCYP3A4.47185506

Palbociclib:Monitorforanincreaseinlovastatinrelatedadversereactionsifcoadministrationwithpalbociclibisnecessary.Palbociclibisa
weaktimedependentinhibitorofCYP3AandlovastatinisasensitiveCYP3A4substrate.286042877434492412755656358768

Pantoprazole:Atorvastatin,lovastatin,andsimvastatinareHMGCoAreductaseinhibitors(statins)recognizedassubstratesandinhibitorsof
thePglycoprotein(Pgp)transportsystem.Likewise,studiesshowthatlansoprazole,omeprazole,andpantoprazolearealsosubstratesand
inhibitorsofPgp.DuetocompetitiveinhibitionofthePgptransportsystem,coadministrationmayleadtoincreasedintestinalabsorption
and/ordecreasedhepaticexcretionofeitherproduct.Theresultingincreaseddrugbioavailabilitycouldleadtoincreasedadverseevents,
includingseriousmyopathiesinthecaseofhigherthannormalstatinplasmaconcentrations.Forexample,Pgpinhibitionwassuspectedina
casereportinvolvingapatientpresentingtotheemergencyroomwithrhabdomyolysis,causingthirddegreeAVblock.Thepatient's
medicationhistoryincludedatorvastatin(>1yearhistory),esomeprazole(6weekhistory),andclarithromycin(500mgx3dosespriorto
admission).Symptomsofweakness,shortnessofbreath,andchestpaincoincidedwiththestartofesomeprazoletherapy.Duetothetimingof
symptomonset,clinicianssuspectedthatesomeprazolelikelyincreasedatorvastatinplasmaconcentrationsleadingtorhabdomyolysisand
furthercomplications.AlthoughcompetitiveinhibitionofCYPisoenzymemetabolismcouldhaveplayedaminorroleintheinteraction,the
mainpathwaywasthoughttobecompetitivePgpinhibition.Cautionisthereforewarrantedwhencombiningatorvastatin,lovastatin,red
yeastrice(structurallysimilartolovastatin),orsimvastatinwithesomeprazole,lansoprazole,omeprazole,orpantoprazole.Substitutingwith
dexlansoprazoleorrabeprazolemayrepresentasaferalternative.Treatmentwithpravastatin,fluvastatin,androsuvastatinmayalsodecrease
theriskofaPgpinteraction.41275412764127741278

Pazopanib:PazopanibisaweakinhibitorofCYP3A4.Coadministrationofpazopanibandlovastatin,aCYP3A4substrate,maycausean
increaseinsystemicconcentrationsoflovastatin.Usecautionwhenadministeringthesedrugsconcomitantly.2860437098

Phenytoin:Phenytoin,aCYP3A4inducer,maydecreasetheefficacyoflovastatin,aCYP3A4substrate.Onecasestudydocumentedan
increaseintotalserumcholesterolconcentrationswhenphenytoinwasadministeredconcurrentlywithanotherHMGCoAreductase
inhibitor,atorvastatin.Totalserumcholesterolconcentrationsthendecreasedwhenphenytoinwasdiscontinued.Monitorforpotential
reducedcholesterolloweringefficacy.280012853528774

Posaconazole:Concurrentuseoflovastatinandposaconazoleiscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,andacute
renalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4inhibitorsincludingposaconazole.If
noalternativetoashortcourseoftreatmentwithposaconazoleisavailable,abriefsuspensionoflovastatintherapyduringsuchtreatmentcan
beconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterolloweringtherapy.28604

Proteaseinhibitors:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Quetiapine:Inapublishedcase,ithasbeenhypothesizedthatthecombinationoflovastatinandquetiapineresultedinprolongationofthe
QTcinterval.ThesuggestedmechanismiscompetitiveinhibitionoftheCYP3A4isoenzymeleadingtoelevatedquetiapineplasma
concentrations.BothlovastatinandquetiapineareCYP3A4substrates.TheQTcintervalreturnedtobaselinewhenthelovastatindosewas
reduced.Theclinicalsignificanceandreproducibilityofthisinteractionisunknown.2860429716

Quinine:LovastatinisaCYP3A4substratetherefore,quininehasthepotentialtoinhibitthemetabolismoflovastatinleadingtoanincreased
potentialofrhabdomyolysis.Patientsreceivingconcomitantlovastatinandquinineshouldbemonitoredcloselyformusclepainorweakness.
Lowerstartingdosesoflovastatinshouldbeconsideredwhilepatientsarereceivingquinine.8189

Raltegravir:Raltegravirusehasbeenassociatedwithelevatedcreatininekinaseconcentrationsmyopathyandrhabdomyolysishavebeen
reported.UseraltegravircautiouslywithdrugsthatincreasetheriskofmyopathyorrhabdomyolysissuchasHMGCoAreductaseinhibitors
(Statins).10381

Ranolazine:Theriskofmyopathyandrhabdomyolysismaybeincreasedinpatientstakingranolazineandlovastatinconcurrentlya
lovastatindosageadjustmentmaybeconsidered.RanolazineinhibitsCYP3AisoenzymesandPglycoproteintransport.Althoughnotstudied,
ranolazinemaytheoreticallyincreaseplasmaconcentrationsofCYP3A4and/orPglycoproteinsubstratessuchaslovastatin.Theplasma
concentrationsofsimvastatin,aCYP3A4substrate,anditsactivemetaboliteareeachincreasedabout2foldinhealthysubjectsreceiving
simvastatin(80mgoncedaily)andranolazine(1000mgtwicedaily).Thedoseofsimvastatinmayhavetobereducedwhenranolazineis
coadministered.Sincelovastatinhasasimilardruginteractionprofilerelativetosimvastatin,itisprudenttoconsiderusinglowerdosesof
lovastatinduringranolazinetherapy.Monitorserumlipidprofileandforsignsandsymptomsofmyopathyduringcoadministration.11350
28604 31938

RedYeastRice:SincecompoundsinredyeastriceclaimtohaveHMGCoAreductaseinhibitoractivity,redyeastriceshouldnotbeusedin
combinationwithHMGCoAreductaseinhibitors.TheadministrationofmorethanoneHMGCoAreductaseinhibitoratonetimewouldbe
duplicativetherapyandperhapsincreasetheriskofdrugrelatedtoxicityincludingmyopathyandrhabdomyolysis.2860429173

Ribociclib:Usecautionifcoadministrationofribociclibwithlovastatinisnecessary,asthesystemicexposureoflovastatinmaybeincreased
resultinginincreaseintreatmentrelatedadversereactions.RibociclibisamoderateCYP3A4inhibitorandlovastatinisaCYP3A4substrate.
286042877434492412755656361816

RibociclibLetrozole:Usecautionifcoadministrationofribociclibwithlovastatinisnecessary,asthesystemicexposureoflovastatinmaybe
increasedresultinginincreaseintreatmentrelatedadversereactions.RibociclibisamoderateCYP3A4inhibitorandlovastatinisaCYP3A4
substrate.286042877434492412755656361816

Rifabutin:Rifampinhasbeenreportedtosignificantlyincreasetheplasmaclearanceanddecreasetheserumconcentrationsofatorvastatin,
simvastatinandfluvastatin,withthepotentialforreducedantilipemicefficacy.Althoughnotstudied,asimilarinteractioncanbeexpected
betweenotherrifamycins(e.g.,rifabutin,rifapentine)andotherHMGCoAreductaseinhibitors(Statins).Toevaluatethisinteraction,
monitorserumlipidconcentrationsduringcoadministrationofrifamycinswithHMGCoAreductaseinhibitors.618761888879

Rifampin:Rifampinhasbeenreportedtosignificantlyincreasetheplasmaclearanceanddecreasetheserumconcentrationsofatorvastatin,
simvastatinandfluvastatin,withthepotentialforreducedantilipemicefficacy.Althoughnotstudied,asimilarinteractioncanbeexpected
betweenotherrifamycins(e.g.,rifabutin,rifapentine)andotherHMGCoAreductaseinhibitors(Statins).Toevaluatethisinteraction,
monitorserumlipidconcentrationsduringcoadministrationofrifamycinswithHMGCoAreductaseinhibitors.2944732067

Rifapentine:Rifampinhasbeenreportedtosignificantlyincreasetheplasmaclearanceanddecreasetheserumconcentrationsof
atorvastatin,simvastatinandfluvastatin,withthepotentialforreducedantilipemicefficacy.Althoughnotstudied,asimilarinteractioncanbe
expectedbetweenotherrifamycins(e.g.,rifabutin,rifapentine)andotherHMGCoAreductaseinhibitors(Statins).Toevaluatethis
interaction,monitorserumlipidconcentrationsduringcoadministrationofrifamycinswithHMGCoAreductaseinhibitors.618761888879

Rifaximin:Althoughtheclinicalsignificanceofthisinteractionisunknown,concurrentuseofrifaximin,aPglycoprotein(Pgp)substrate,
andlovastatin,aPgpinhibitor,maysubstantiallyincreasethesystemicexposuretorifaximincautionisadvisedifthesedrugsmustbe
administeredtogether.Duringoneinvitrostudy,coadministrationwithcyclosporine,apotentPgpinhibitor,resultedinan83foldand124
foldincreaseinthemeanCmaxandAUCofrifaximin,respectively.Inpatientswithhepaticimpairment,theeffectsofreducedmetabolism
andPgpinhibitionmayfurtherincreaseexposuretorifaximin.29289

Ritonavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Rivaroxaban:Coadministrationofrivaroxabanandlovastatinmayresultinincreasesinrivaroxabanexposureandmayincreasebleedingrisk.
LovastatinisaninhibitorofPgp,andrivaroxabanisasubstrateofPgp.Ifthesedrugsareadministeredconcurrently,monitorthepatientfor
signsandsymptomsofbleeding.11350412754485453355506

Sapropterin:Cautionisadvisedwiththeconcomitantuseofsapropterinandlovastatinascoadministrationmayresultinincreasedsystemic
exposureoflovastatin.LovastatinisasubstrateforthedrugtransporterPglycoprotein(Pgp)invitrodatashowthatsapropterinmay
inhibitPgp.Ifthesedrugsareusedtogether,closelymonitorforincreasedsideeffectsoflovastatin.286042877433635

Saquinavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Siltuximab:CautioniswarrantedinpatientswithcoadministeredCYP3A4substrates,suchaslovastatin,inwhichadecreasedeffectwould
beundesirable.CytochromeP450sintheliveraredownregulatedbyinfectionandinflammationstimuli,includingcytokinessuchas
interleukin6(IL6).InhibitionofIL6signalingbysiltuximabmayrestoreCYP450activitiestohigherlevelsleadingtoincreasedmetabolism
ofdrugsthatareCYP450substratesascomparedtometabolismpriortotreatment.TheeffectofsiltuximabonCYP450enzymeactivitycan
persistforseveralweeksafterstoppingtherapy.57062

Simeprevir:Althoughcoadministrationoflovastatinwithsimeprevirhasnotbeenstudied,useofthesedrugstogetherisexpectedtoincrease
lovastatinexposure.Ifthesedrugsaregiventogether,titratethelovastatindosecarefullyandusethelowesteffectivedose.Closelymonitor
forstatinassociatedadversereactions,suchasmyopathyandrhabdomyolysis.56471

SofosbuvirVelpatasvir:Usecautionwhenadministeringvelpatasvirwithlovastatin.Takingthesemedicationstogethermayincreasethe
plasmaconcentrationsofbothdrugs,potentiallyresultinginadverseevents.Bothdrugsaresubstratesandinhibitorsofthedrugtransporter
Pglycoprotein(Pgp).286042877434492412755656360911

St.John'sWort,Hypericumperforatum:St.John'sWortappearstoinduceseveralisoenzymesofthehepaticcytochromeP450enzyme
system.CoadministrationofSt.John'swortcoulddecreasetheefficacyofsomemedicationsmetabolizedbytheseenzymesincluding
lovastatin.4935

Streptogramins:DalfopristinquinupristinhasbeenshowntoinhibitCYP3A4andmaydecreasetheeliminationoflovastatin,aCYP3A4
substrate.471852215335

Tacrolimus:TheriskofdevelopingmyopathyduringtherapywithHMGCoAreductaseinhibitorsmaybeincreasedwhenusedwith
tacrolimus.29442

Telaprevir:Theconcurrentuseoflovastatinandtelapreviriscontraindicatedduetothepotentialforserious/lifethreateningreactions.
TelaprevirisaninhibitorofCYP3A4,whichisresponsiblelovastatinmetabolism.Coadministrationmayresultinlargeincreasesinlovastatin
serumconcentrations,whichcouldcauseadverseeventssuchasmyopathyandrhabdomyolysis.28604443935335

Telbivudine:TheriskofmyopathymaybeincreasedifanHMGCoAreductaseinhibitoriscoadministeredwithtelbivudine.Monitorpatients
foranysignsorsymptomsofunexplainedmusclepain,tenderness,orweakness,particularlyduringperiodsofupwarddosagetitration.32827

Telithromycin:Concurrentuseoflovastatinandtelithromyciniscontraindicated.Theriskofdevelopingmyopathy,rhabdomyolysis,and
acuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithstrongCYP3A4inhibitorsincluding
telithromycin.Ifnoalternativetoashortcourseoftreatmentwithtelithromycinisavailable,abriefsuspensionoflovastatintherapyduring
suchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterollowering
therapy.2815628604

TelotristatEthyl:Usecautionifcoadministrationoftelotristatethylandlovastatinisnecessary,asthesystemicexposureoflovastatinmaybe
decreasedresultinginreducedefficacyexposuretotelotristatethylmayalsobeincreased.Ifthesedrugsareusedtogether,monitorpatients
forsuboptimalefficacyoflovastatinaswellasanincreaseinadversereactionsrelatedtotelotristatethyl.Considerincreasingthedoseof
lovastatinifnecessary.LovastatinisaCYP3A4substrate.ThemeanCmaxandAUCofanothersensitiveCYP3A4substratewasdecreasedby
25%and48%,respectively,whencoadministeredwithtelotristatethylthemechanismofthisinteractionappearstobethattelotristatethyl
increasestheglucuronidationoftheCYP3A4substrate.Additionally,theactivemetaboliteoftelotristatethyl,telotristat,isasubstrateofP
glycoprotein(Pgp)andlovastatinisaPgpinhibitor.Exposuretotelotristatethylmayincrease.286042877434492412755656361795

Temsirolimus:Usecautionifcoadministrationoftemsirolimuswithlovastatinisnecessary,andmonitorforanincreaseintemsirolimusand
lovastatinrelatedadversereactions.TemsirolimusisaPglycoprotein(Pgp)substrate/inhibitorinvitro,whilelovastatinisalsoaPgp
substrate/inhibitor.PharmacokineticdataarenotavailableforconcomitantuseoftemsirolimuswithPgpinhibitorsorsubstrates,but
exposuretobothlovastatinandtemsirolimus(andactivemetabolite,sirolimus)islikelytoincrease.286042877434492412755058656563

TenofovirAlafenamide:Cautionisadvisedwhenadministeringtenofoviralafenamideconcurrentlywithlovastatin,ascoadministrationmay
resultinelevatedtenofoviralafenamideplasmaconcentrations.InhibitorsofthedrugtransporterPglycoprotein(Pgp),suchaslovastatin,
mayincreaseabsorptionoftenofoviralafenamide,aPgpsubstrate.Ifthesemedicationsareadministeredtogether,monitorfortenofovir
associatedadversereactions.Ofnote,whentenofoviralafenamideisadministeredaspartofacobicistatcontainingproduct,itsavailabilityis
increasedbycobicistatandafurtherincreaseoftenofoviralafenamideconcentrationsisnotexpecteduponcoadministrationofanadditional
Pgpinhibitor.286046061460688

Tenofovir,PMPA:Cautionisadvisedwhenadministeringtenofovir,PMPA,aPglycoprotein(Pgp)substrate,concurrentlywithinhibitorsof
Pgp,suchaslovastatin.Coadministrationmayresultinincreasedabsorptionoftenofovir.Monitorfortenofovirassociatedadversereactions.
28193

Teriflunomide:Concurrentuseofteriflunomide,aninhibitorofthehepaticuptakeorganicaniontransportingpolypeptideOATP1B1,with
someHMGCoAreductaseinhibitors(Statins),includingatorvastatin,lovastatin,pitavastatin,pravastatin,rosuvastatin,orsimvastatinmay
increasetheAUCofthestatin.Administrationofcyclosporine,anotherOATP1B1inhibitor,increasedtheplasmaAUCofpravastatin9.9fold.
Additivehepatotoxicitymayoccur.Cautionshouldalsobeexercisedwhenusingcombinationdosageforms,suchasamlodipineatorvastatin,
ezetimibesimvastatin,lovastatinniacin,niacinsimvastatin,andsimvastatinsitagliptin.Monitorpatientsforsignsofmyopathyor
hepatotoxicity.364515179451834

Ticagrelor:Avoidlovastatindoses>40mg/daywhenusedconcomitantlywithticagrelorasconcomitantusewillresultinhigherserum
concentrationsoflovastatin.LovastatinismetabolizedbyCYP3A4andticagrelorisaninhibitorofCYP3A4.Inaddition,coadministrationof
ticagrelorandlovastatinorlovastatinniacinmayresultinincreasedexposuretoticagrelorwhichmayincreasethebleedingrisk.Ticagreloris
aPglycoprotein(Pgp)substrateandlovastatinisaPgpinhibitor.Nodoseadjustmentisrecommendedbythemanufacturerofticagrelor.
Usecombinationwithcautionandmonitorforevidenceofbleeding.4495156563

Tigecycline:CoadministrationofPglycoprotein(Pgp)inhibitors,suchaslovastatin,mayincreasetigecyclineserumconcentrations.Based
onaninvitrostudy,tigecyclineisaPgpsubstratehowever,thepotentialcontributionofPgpmediatedtransporttotheinvivodisposition
oftigecyclineisnotknown.28604287743129956563

Tipranavir:Concurrentuseoflovastatinandantiretroviralproteaseinhibitorsiscontraindicated.Theriskofdevelopingmyopathy,
rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministeredconcomitantlywithantiretroviralprotease
inhibitors.LovastatinisasubstrateofCYP3A4andantiretroviralproteaseinhibitorsarestronginhibitorsofCYP3A4therefore,
coadministrationmayresultinsubstantialincreasesinplasmaconcentrationsoflovastatin.28604

Tocilizumab:Invitro,tocilizumabhasthepotentialtoaffectexpressionofmultipleCYPenzymes,includingCYP3A4.A57%decreasein
simvastatinexposurewasnoted1weekafterasingletocilizumabdosesimvastatinisaCYP3A4substrate.Utilizecautionwhenusing
tocilizumabincombinationwithCYP3A4substratedrugswhereadecreaseineffectivenessisundesirablesuchaslovastatin.38283

Topotecan:Avoidtheconcomitantuseoflovastatin,aPglycoprotein(Pgp)inhibitor,withoraltopotecan,aPgpsubstratePgpinhibitors
havelessofaneffectonintravenoustopotecanandthesemaybecoadministeredwithcaution.Ifcoadministrationoflovastatinandoral
topotecanisnecessary,carefullymonitorforincreasedtoxicityoftopotecan,includingseveremyelosuppressionanddiarrheathisalso
appliestocombinationproductscontaininglovastatin,suchaslovastatinniacin.Inapharmacokineticcohortstudy,coadministrationoforal
topotecanwithapotentPgpinhibitor(n=8)increasedtheCmaxandAUCoftopotecanby2to3fold(p=0.008)coadministrationwith
intravenoustopotecan(n=8)increasedtotaltopotecanexposureby1.2fold(p=0.02)andtopotecanlactoneby1.1fold(notsignificant).
10430 28604 28774 33536 34492 41275 46322 56563

TrandolaprilVerapamil:Coadministrationofverapamilandlovastatinincreasestheriskformyopathy/rhabdomyolysis,particularlywith
higherdosesoflovastatin.Inpatientstakingverapamil,theinitiallovastatindoseshouldnotexceed10mg/dayPO.WhiletheFDAapproved
productlabelingforlovastatinproductsrecommendsamaximumlovastatindosageof20mg/daywhentheseagentsareusedtogether,the
productlabelingforverapamilsuggestsamaximumlovastatindosageof40mg/day.Thebenefitsoftheuseoflovastatininpatientstaking
verapamilshouldbecarefullyweighedagainsttherisksofthiscombination.Specificdosagerecommendationsforpediatricpatientsreceiving
thiscombinationarenotavailable.2827328604

Ulipristal:InvitrodataindicatethatulipristalmaybeaninhibitorofPglycoprotein(Pgp)atclinicallyrelevantconcentrations.Thus,co
administrationofulipristalandPgpsubstratessuchaslovastatinmayincreaselovastatinconcentrationsusecaution.Withsingledosesof
ulipristalforemergencycontraceptionitisnotclearthisinteractionwillhaveclinicalconsequence.Intheabsenceofclinicaldata,co
administrationofulipristal(whengivendaily)andPgpsubstratesisnotrecommended.4156950623

Vandetanib:Usecautionifcoadministrationofvandetanibwithlovastatinisnecessary,duetoapossibleincreaseinlovastatinrelated
adversereactions.LovastatinispartiallyasubstrateofPglycoprotein(Pgp).CoadministrationwithvandetanibincreasedtheCmaxandAUC
ofdigoxin,anotherPgpsubstrate,by29%and23%,respectively.2860428774344924390156563

Vemurafenib:Concomitantuseofvemurafenibandlovastatinmayresultinalteredconcentrationsoflovastatinandincreasedconcentrations
ofvemurafenib.Vemurafenibisasubstrate/inducerofCYP3A4andasubstrate/inhibitorofPglycoprotein(PGP).Lovastatinisasubstrateof
CYP3A4andasubstrate/inhibitorofPGP.Usecautionandmonitorpatientsfortoxicityandefficacy.11350412754533553355506

Venetoclax:Avoidtheconcomitantuseofvenetoclaxandlovastatin.VenetoclaxisasubstrateofPglycoprotein(Pgp)andmaybeaPgp
inhibitorattherapeuticdoselevelsinthegutlovastatinisasubstrateandaninhibitorofPgp.Consideralternativeagents.Ifconcomitant
useofthesedrugsisrequired,reducethevenetoclaxdosagebyatleast50%(maximumdoseof200mg/day)andconsideradministering
lovastatinatleast6hoursbeforevenetoclax.Iflovastatinisdiscontinued,wait2to3daysandthenresumetherecommendedvenetoclax
dosage(orpriordosageifless).Monitorpatientsforsignsandsymptomsofvenetoclaxtoxicitysuchashematologictoxicity,GItoxicity,and
tumorlysissyndrome.Inadruginteractionstudy(n=11),thevenetoclaxCmaxandAUCvalueswereincreasedby106%and78%,
respectively,whenaPgpinhibitorwascoadministeredinhealthysubjects.28774344925656360706

Verapamil:Coadministrationofverapamilandlovastatinincreasestheriskformyopathy/rhabdomyolysis,particularlywithhigherdosesof
lovastatin.Inpatientstakingverapamil,theinitiallovastatindoseshouldnotexceed10mg/dayPO.WhiletheFDAapprovedproduct
labelingforlovastatinproductsrecommendsamaximumlovastatindosageof20mg/daywhentheseagentsareusedtogether,theproduct
labelingforverapamilsuggestsamaximumlovastatindosageof40mg/day.Thebenefitsoftheuseoflovastatininpatientstakingverapamil
shouldbecarefullyweighedagainsttherisksofthiscombination.Specificdosagerecommendationsforpediatricpatientsreceivingthis
combinationarenotavailable.2827328604

VincristineLiposomal:LovastatininhibitsPglycoprotein(Pgp),andvincristineisaPgpsubstrate.Coadministrationcouldincrease
exposuretovincristinemonitorpatientsforincreasedsideeffectsifthesedrugsaregiventogether.2860428774346565143256563

Vincristine:LovastatininhibitsPglycoprotein(Pgp),andvincristineisaPgpsubstrate.Coadministrationcouldincreaseexposureto
vincristinemonitorpatientsforincreasedsideeffectsifthesedrugsaregiventogether.2860428774346565143256563

Vinorelbine:Cautioniswarrantedwhenlovastatinisadministeredwithvinorelbineasthereisapotentialforelevatedvinorelbine
concentrationsthismayalsoapplytocombinationproductscontaininglovastatin,includinglovastatinniacin.Monitorpatientsforan
earlieronsetand/oranincreasedseverityofadverseeffectsincludingneurotoxicityandmyelosuppression.VinorelbineisasubstrateofP
glycoprotein(Pgp)andlovastatinisaninhibitorofPgp.286042877434492412755656359600

Voriconazole:Theriskofdevelopingmyopathy,rhabdomyolysis,andacuterenalfailureissubstantiallyincreasediflovastatinisadministered
concomitantlywithCYP3A4inhibitors(e.g.,voriconazole).Althoughnotstudiedclinically,voriconazolehasbeenshowntoinhibitlovastatin
metabolisminvitro.Therefore,itislikelythatcoadministrationofvorizonazolewillresultinincreasedplasmaconcentrationsoflovastatin.
Accordingtothemanufacturer,adosereductionoflovastatinshouldbeconsideredifthedrugsarecoadministered.Becausepravastatinis
notsignificantlymetabolized,itislesslikelytointeractwiththeazoleantifungals.AbriefsuspensionofHMGCoAreductaseinhibitor
therapyduringsuchtreatmentcanbeconsideredastherearenoknownadverseconsequencestobriefinterruptionsoflongtermcholesterol
loweringtherapyhowever,somemanufacturersrecommenddoseadjustmentofthestatin.Administervoriconazolecautiouslytopatients
receivingHMGCoAreductaseinhibitors.28604344474882533453355506

Warfarin:MonitorINRcarefullyinpatientstakingwarfarinwhenlovastatinisinitiatedoralovastatindosageadjustmentismade.
Lovastatin'sinfluenceonwarfarin'sclinicaleffectsisunclear.Bleedingand/orprolongedprothrombintimehavebeenreportedinafew
patientswhenlovastatinwastakenconcurrentlywithcoumarinanticoagulants.However,onesmallclinicaltrialfoundnoeffecton
prothrombintimewhenlovastatinwasgiventopatientsreceivingwarfarin.AnotherHMGCoAreductaseinhibitorwasfoundtoincreasethe
INRby<2secondsinhealthysubjectstakinglowdosesofwarfarin.Alternatively,itappearsthatpravastatinandatorvastatinmaybeless
likelytosignificantlyinteractwithwarfarinbasedondruginteractionstudies.2854928604

Zafirlukast:ZafirlukastinhibitstheCYP3A4isoenzymesandshouldbeusedcautiouslyinpatientsstabilizedondrugsmetabolizedby
CYP3A4,suchaslovastatin.494853355506

Zileuton:ZileutonismetabolizedbythecytochromeP450isoenzyme3A4andcouldpotentiallycompetewithotherCYP3A4substrates
includinglovastatin.5415

Zonisamide:ZonisamideisaweakinhibitorofPglycoprotein(Pgp),andlovastatinisasubstrateofPgp.Thereistheoreticalpotentialfor
zonisamidetoaffectthepharmacokineticsofdrugsthatarePgpsubstrates.Usecautionwhenstartingorstoppingzonisamideorchanging
thezonisamidedosageinpatientsalsoreceivingdrugswhicharePgpsubstrates.2860428774288433449241275

Lastrevised:June13,2017

AdverseReactions
abdominalpain

alopecia

amnesia

anaphylactoidreactions

angioedema

anxiety

arthralgia

asthenia

backpain

blurredvision
cataracts

chestpain(unspecified)

chills

cholestasis

cirrhosis

confusion

constipation

depression

diabetesmellitus

diarrhea

dizziness

drowsiness

dysgeusia

dyspepsia

dyspnea

elevatedhepaticenzymes

eosinophilia

erythemamultiforme

fatigue

fever

flatulence

flushing

gastroesophagealreflux

gynecomastia

headache

hemolyticanemia

hepaticfailure

hepaticnecrosis

hepatitis

hepatoma

hyperglycemia

immunemediatednecrotizingmyopathy

impotence(erectiledysfunction)

infection

influenza
insomnia

jaundice

leukopenia

libidodecrease

lupuslikesymptoms

malaise

memoryimpairment

musclecramps

myalgia

myasthenia

myoglobinuria

myopathy

nausea

ocularirritation

pancreatitis

paresthesias

peripheralneuropathy

photosensitivity

pruritus

purpura

rash(unspecified)

renalfailure(unspecified)

renaltubularobstruction

rhabdomyolysis

sinusitis

StevensJohnsonsyndrome

thrombocytopenia

toxicepidermalnecrolysis

tremor

urticaria

vasculitis

vertigo

vomiting

weakness

xerostomia
Amyotrophiclateralsclerosis(ALS,LouGehrig'sDisease)hasbeenreportedtotheFDAinahigherthanexpectednumberofpatientstaking
statinslikelovastatin.ALSisaprogressivemotorneurondisorderwithsymptomssuchasdifficultywalkingorstanding,difficultywithfine
motorskills,atrophyoftongueandhandmuscles,dysphagia,dysarthria,andmuscleparalysis.DuetotheseriousnessofALSandthe
extensiveuseofstatins,FDAfurtherexamineddatafrom41longtermcontrolledclinicaltrials.Theresultsofthereviewshowednoincreased
incidenceofALSinpatientstreatedwithastatincomparedwithplacebo.34644Specifically,9ofapproximately64,000patientstreatedwitha
statin(4.2casesper100,000patientyears)and10ofapproximately56,000patientstreatedwithplacebo(5caseper100,000patientyears)
werediagnosedwithALS.FDAisexaminingthefeasibilityofperformingadditionalepidemiologicstudiestofurtherexaminetheincidence
andclinicalcourseofALSinpatientstakingstatins.

ThyroidfunctionabnormalitiesandelevationsinbilirubinhavebeenreportedwithHMGCoAreductaseinhibitorsalthoughthiseffectisnot
necessarilyassociatedwithlovastatinuse.28604

Toxicitytotheskeletalmuscleoccursinfrequentlybutcanbeaseriousadversereactiontolovastatintherapy.Statininducedmyopathyis
generallydoserelated.Ingeneral,rhabdomyolysisisarare(<1/100,000prescriptions)complicationofHMGCoAreductaseinhibitor
('statin')therapy.Myopathy,rhabdomyolysisandacuterenalfailure(unspecified)(duetorenaltubularobstruction,myoglobinuria)have
beenreportedrarelywiththeuseoflovastatin,buttheriskisincreasedwhenlovastatinisusedincombinationwithdrugsknowntointeract
withHMGCoAreductaseinhibitors.Rarely,immunemediatednecrotizingmyopathy(IMNM)hasbeenreportedwithstatinuse.IMNMis
characterizedby:proximalmuscleweaknessandelevatedserumcreatinekinase,whichpersistdespitediscontinuationofstatintreatment
musclebiopsyshowingnecrotizingmyopathywithoutsignificantinflammationandimprovementwithimmunosuppressiveagents.
Rhabdomyolysismayoccuranytimeduringdrugtreatmentandtheriskmaybeincreasedbyanumberofconfoundingfactorsincludingage,
concomitantdrugtherapy,renaldysfunction,andconcomitantdiseasestates.Manycasesresultinhospitalizationandaneedfordialysisfor
treatment.Vigilantclinicalmonitoringduringprescribingcanhelplimitseriousadverseevents.Patientsshouldbemonitoredforsymptoms
ofmyopathyorrhabdomyolysis(unexplainedmyalgia,drowsiness/lethargy,fatigue,asthenia/weakness,fever,and/ormyasthenia)andCPK
serumconcentrations.Elevationsofcreatininephosphokinase(CPK)ofatleasttwicethenormalon1ormoreoccasionoccurin
approximately11%ofpatients.Duringclinicaltrials,myalgiahasbeenreportedin1.83%ofpatients,musclecrampshavebeenreportedin
0.61.1%ofpatients,andastheniahasbeenreportedin1.23%ofpatients.2860443289Theriskofmyopathyisdoserelated.IntheEXCEL
study,onecaseofmyopathyoccurredamong4933patientsreceiving2040mg/daylovastatinwhereas4of1649patientsexperienced
myopathyatthe80mg/daydosage.Themyopathyriskisgreateriflovastatinisadministeredwithgemfibrozil,lipidloweringdosesof
nicotinicacid(>=1g/day),CYP3A4inhibitors,orcyclosporine(seeDrugInteractions).Myopathyormyositiscanreverseiftherapyis
discontinued.Astudyoflovastatintherapyinmorethan3,300womenrevealedthatmyopathyoccurredtooinfrequentlytoaccuratelyapply
statisticalanalysis.23471LovastatinshouldbediscontinuedimmediatelyinanypatientwhodevelopsmyopathyorelevationsinCPK.

AdverseGIeffectsoccurwithlovastatinusebutareusuallymild.Theyincludenausea(1.92.5%),dyspepsia(11.6%),constipation(2
3.5%),diarrhea(23%),flatulence(3.74.5%),andabdominalpain(22.5%).Gastroesophagealreflux,xerostomia,andvomitingalsohave
beenreportedin0.51%ofpatientsinclinicaltrialsofimmediatereleaselovastatin.AnorexiahasbeenreportedwithHMGCoAreductase
inhibitors.2860443289

Althoughrare,severehepatotoxicitymayoccurduringHMGCoAreductaseinhibitortherapy.Hepatitis,fattychangesoftheliver,cholestasis
withjaundice,pancreatitis,andrarely,cirrhosis,fulminanthepaticnecrosis,hepaticfailure,andhepatomahavebeenreportedduringtherapy
withHMGCoAreductaseinhibitors.Lovastatintherapyhasbeenassociatedwithelevatedhepaticenzymes.Liverfunctiontests(LFTs)
shouldbeperformedpriortoinitiationoftherapywithlovastatinandthenrepeatedasclinicallyindicated.Ifseriousliverinjurywithclinical
symptomsand/orhyperbilirubinemiaorjaundiceoccursduringtreatmentwithlovastatin,promptlyinterrupttherapy.Ifanalternateetiology
isnotfound,donotrestartlovastatin.Persistentelevationsofserumtransaminases(tomorethan3timesupperlimitofnormal)were
reportedin1.9%ofpatientsreceivinglovastatinfor>=1yearduringearlyclinicaltrialsenzymeelevationsdecreasetopretreatment
concentrationsafterdrugdiscontinuation.Thisincreaseinserumtransaminasesusuallyoccurred312monthsafterinitiationoftherapyand
wasnotassociatedwithjaundiceorothersymptomsofliverdisease.Inonestudy,theincidenceofpersistentincreasesinserum
transaminasesover48weekswas0.1%forplacebo,0.1%for20mg/day,0.9%for40mg/day,and1.5%for80mg/day.Inanotherstudywith
amedianof5.1yearsoffollowup,persistentincreasesinserumtransaminaseswereseenin0.7%ofpatientstaking20mg/dayand0.4%of
patientstaking40mg/dayoflovastatin.28604

Headacheisthemostcommoncentralnervoussystemeffectassociatedwithlovastatinuse,occurringin2.18%ofpatientstaking
immediatereleaseandextendedreleaseformulations(placebo2.76%).Dizzinesshasalsobeenreportedin0.52%oflovastatintreated
patients(0.76%placebo).Insomniaandparesthesiasalsohavebeenreportedduringlovastatintherapy(0.51%).Rarecasesofcognitive
impairment(e.g.,memoryloss,forgetfulness,amnesia,memoryimpairment,confusion)havebeenassociatedwiththeuseofstatins.Areview
ofavailabledatabytheFDAdidnotfindanassociationbetweentheeventandaspecificstatin,statindose,concomitantmedication,orageof
thepatient.Ingeneral,postmarketingreportsdescribedpatientsovertheageof50yearswhoexperiencednotable,butilldefinedmemory
lossorimpairmentthatwasreversibleuponstatindiscontinuation.Thecasesdidnotappeartobeassociatedwithprogressiveorfixed
dementia.Thetimetosymptomonset(1daytoyears)andresolution(median3weeks)isvariable.49066Otherneurologicaleffectsreported
withHMGCoAreductaseinhibitorsandnotnecessarilyassociatedwithlovastatinuseincludedysgeusia,impairmentofextraocular
movement,facialparesis,tremor,vertigo,peripheralnervepalsy,psychicdisturbances,anxiety,anddepression.2860443289

Arthralgiahasbeenreportedduringtherapywithlovastatin.Duringclinicaltrialsofimmediatereleaselovastatin,arthralgiawasreportedin
0.51%ofpatientsreceivinglovastatin.Incontrolledtrialsofextendedreleaselovastatin(e.g.,vs.placeboandvs.lovastatinimmediate
release),arthralgiawasreportedin6%ofpatientstakingimmediatereleaselovastatin,5%ofpatientsreceivingextendedreleaselovastatin
and6%ofthosetakingplacebo.2860443289

Allergicreactionscanoccurwithlovastatintherapy.Rash(unspecified)occursin0.81.3%ofpatientsreceivinglovastatintherapyvs.0.7%
forplacebo.28604Avarietyofgeneralskinchanges(i.e.,nodules,discoloration,drynessofmucousmembranes,changestohair/nails)have
beenreportedduringHMGCoAreductaseinhibitortherapy.Alopeciaandpruritushavebeenreportedin0.51%ofpatientsreceiving
lovastatin.AnapparenthypersensitivitysyndromehasbeenreportedrarelywithHMGCoAreductaseinhibitorswhichhasincludedoneor
moreofthefollowingfeaturesoranaphylactoidreactions:anaphylaxis,angioedema,lupuslikesymptoms,polymyalgiarheumatica,
dermatomyositis,vasculitis,purpura,thrombocytopenia,leukopenia,hemolyticanemia,positiveANA,ESRincrease,eosinophilia,arthritis,
arthralgia,urticaria,asthenia,photosensitivity,fever,chills,flushing,malaise,dyspnea,toxicepidermalnecrolysis,erythemamultiforme,and
StevensJohnsonsyndrome.28604

Blurredvisionhasbeenreportedin0.91.2%oflovastatintreatedpatients(vs.0.8%placebo).Ocularirritationhasbeenreportedin0.51%
ofpatientsinlovastatinclinicaltrials.OtheroculareffectsreportedwithHMGCoAreductaseinhibitorsandnotnecessarilyassociatedwith
lovastatinuseincludeprogressionofcataracts(lensopacities),andophthalmoplegia.28604

AnassociationbetweenHMGCoAreductaseinhibitors(statins),includinglovastatin,andperipheralneuropathyhasbeenreportedinthe
literature(caseseries,casecontrolstudies,cohortstudies).3292932930InanestedcasecontrolstudyofaDanishpopulation,theoddsratio
foridiopathicperipheralneuropathyin166patientsthateverorwerecurrentlytakingastatin,was3.7(95%CI1.87.6)32930similarresults
havebeenfoundinotherpopulationbasedstudies,althoughthenumberofpatientsstudiedwassignificantlysmaller.Casereportsandseries
indicatethattheonsetofneuropathyistypically>1yearafterdruginitiationandisreversiblewithdrugdiscontinuation.However,cases
describingirreversibleneuropathyarealsoreported.3292632930Theadverseeffectappearstobeaclasseffectbecauseinallcases,whena
patientiseitherrechallengedortreatedwithadifferentstatin,thesymptomsofneuropathyreturn.Whilethedataappeartosupportan
associationbetweenHMGCoAreductaseinhibitorsandperipheralneuropathy,theincidenceisrareandestimatedtobeapproximately1per
14,000personyears.Furthermore,acausalrelationshipcannotbedefinitivelyestablishedbasedontheobservationalnatureoftheavailable
data.329263292932930Thebenefitsofstatintherapyfaroutweighanyriskofperipheralneuropathyhowever,untilmoreinformationis
available,healthcareprovidersshouldbeawareofthisadverseeffect.

IncreasedhemoglobinA1candfastingserumglucose(hyperglycemia)havebeenreportedduringtherapywithHMGCoAreductase
inhibitors.28604Ametaanalysisof13statintrialswith91,140participantsshoweda9%increaseinthelikelihoodofthedevelopmentof
diabetes(OR1.0995%CI1.021.17).Theincidenceofdiabeteswashigherinhighriskpatients(i.e.,age7082yearswithorathighriskof
cardiovasculardisease,myocardialinfarctionwithinthelast6months,orheartfailure)comparedtopatientswithlowdiabetesrisk(i.e.,low
BMI).39866Additionally,ananalysisofthedatafromtheWomen'sHealthInitiative(WHI)trialfoundthatstatinuseinpostmenopausal
womenisassociatedwithanincreasedriskofnewonsetdiabetesmellitus(multivariateadjustedHR1.4895%CI1.381.59).49063No
differenceintheriskfordiabetesbetweenstatinswasdetectedineitheranalysis.Becausetheuseofstatinshasbeenassociatedwith
significantbenefitforcardiovascularriskreductionandallcausemortalityatcomparableratesindiabeticandnondiabeticpatients49064,
nochangestoclinicalpracticeguidelineshavebeenrecommendedineitherpopulation.However,theincreasedriskofdiabetesshouldbe
consideredwheninitiatinglovastatintherapyinpatientsatlowriskforcardiovasculareventsandinpatientgroupswherethecardiovascular
benefitofstatintherapyhasnotbeenestablished.39866

Duringclinicalstudies,infectionwasreportedin11%ofpatientstakingextendedreleaselovastatinand16%ofthosetakingimmediate
releaselovastatin(placebo=9%).Sinusitiswasreportedin4%and6%,respectively(placebo=3%),andurinarytractinfectionwasreported
in2%and3%,respectively(placebo=6%).Influenza(reportedasflusyndrome)wasreportedin5%ofpatientstakingeitherformulation
(placebo=3%).43289

Duringclinicalstudies,painwasreportedin3%ofpatientstakingextendedreleaselovastatinand5%ofthosetakingimmediaterelease
lovastatin(placebo=0%).Backpainwasreportedin5%ofpatientstakingeitherformulation(placebo=3%).Legpainandshoulderpain
werereportedin0.51%ofpatientsduringclinicaltrialsofimmediatereleaselovastatin.Accidentalinjurywasreportedin6%ofpatients
receivingextendedreleaselovastatinandin4%ofthosetakingimmediatereleaselovastatin(placebo=9%).2860443289

Duringclinicaltrialsoflovastatin,chestpain(unspecified)wasreportedin0.51%ofpatients.28604

ThefollowingreproductiveeffectshavebeenreportedwithHMGCoAreductaseinhibitorsandarenotnecessarilyassociatedwithlovastatin
usegynecomastia,libidodecrease,impotence(erectiledysfunction).28604

Lastrevised:November7,2012

Classifications
HMGCoAreductaseinhibitors

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GlobalDrugNames
Argentina Hipovastin(Gador)
Loriter(Elvetium)
Mevlor(MSD)
 Sivlor(Sidus)

Austria Mevacor(MSD)

Brazil Lipoclin(NeoQuimica)
Lovasc(Klinger)
Lovast(Teuto)
Lovaton(Royton)
Lovax(Cellofarm)
Mevacor(MSD)
Mevalip(Teuto)
Minor(Biosintetica)
Neolipid(Biobras)
Reducol(MSD)
Redustatin(UniaoQuimica)

Canada Mevacor(MerckFrosst)

Chile Colevix(Royal)
Hiposterol(LaboratoriosChile)
Lispor(Medipharm)
Lovacol(Saval)
Mevacor(MSD)
NijTerol(Deutsche)
Sanelor(Sanitas)

China AiLeTing(Qilu)
Deolip(Hisun)
DuLe(JinSangZi)
Gengxian(Dongyu)
JunNing(YangtzeRiver)
LeHuo(Tiancifu)
Lefuxin(Livzon)
LuoZhiDa(Ruibang)
Luohuaning(NCPC)
Meixinjie(Winsunny)
MingWeiXin(HaiKang)
SuErQing(Hayao)
SuXin(Suzhong)
XinLu(LukangChenxin)
XueQing(Daxin)

CzechRepublic Holetar(KRKA)
Lovacard(Leciva)
Medostatin(Medochemie)
Mevacor(MSD)
Rancor(Ranbaxy)

Denmark Lipivas(MSD)
Lovacodan(Stada)
Lovastad(KRKA)
Mevacor(MSD)

Finland Lovacol(Orion)
Mevacor(MSD)

Germany Lova(TAD)
Lovabeta(Betapharm)
Lovadura(Merckdura)
Lovagamma(Worwag)
 Lovahexal(Hexal)
Mevinacor(MSD)

Greece Aurostatin(Aurora)
BLovatin(Medicus)
Cecural(Demo)
Ilopar(Pharmanel)
Liferzit(Medinova())
Lipidless(Angelini)
Lostin(Pharmathen)
Lovadrug(MedOne)
Lovapen(Elpen())
Lovasten(Vocate)
Lovatex(Gap)
Lovatop(PhoinixPharm())
Lowlipid(Alapis)
Medovascin(Medochemie)
Mevacor(Vianex())
Mevastin(Genepharm)
Mevinol(Vianex())
Misodomin(Kleva)
Nabicortin(Help)
Terveson(Doctum)
Velkalov(Velka)
Viking(Rafarm)

HongKong Ellanco(Duopharma)
Lofacol(Dexa)
Lomar(Aegis)
Medostatin(Medochemie)
Mevacor(MSD)
Ovastar(Sinil)

Hungary Mevacor(MSD)
Stoplip(Apotex)

India Aztatin(Sun)
Elstatin(Glenmark)
Favolip(SarabhaiPiramal)
Lestric(Ranbaxy)
Lipistat(RPG)
Lochol(Micro)
Lostatin(Reddy)
Lotin(Intas)
Lova(Orchid)
Lovacard(Cipla)
Lovadac(Zydus)
Lovalip(Cadila)
Lovameg(Alembic)
Lovastat(Torrent)
Lovastrol(Medley)
Lovatin(Intas)
Lovex(Lupin)
ProHDL(Wockhardt)
Rovacor(Ranbaxy)

Indonesia Cholvastin(Sanbe)
Justin(Ifars)
Lipovas(TempoScanPacific)
Lofacol(Ferron)
 Lotivas(Ethica)
Lotyn(Interbat)
Lovatrol(Fahrenheit)

Israel Lovalip(MSD)

Italy Lovinacor(Innova)
Rextat(Recordati)
Tavacor(Savio)

Malaysia Ellanco(CCM)
Lestric(Ranbaxy)
Lostatin(Reddy)
Lovarem(Remedica)
Lovastin(YSP)
Medostatin(Medochemie)
Mevacor(MSD)

Mexico Casbame(Bajamed)
Dilucid(Collins)
Liperol(Rayere)
Mevacor(MSD)

Norway Mevacor(MSD)

Poland Anlostin(Biovena)
ApoLova(Apotex)
Liprox(Biofarm)
Lovasterol(Polpharma)
Lovastin(GedeonRichter)

Portugal Flozul(Farlab)
Lipdaune(Sofex)
Lipus(BAFarma)
Mevinacor(MSD)
Mevlor(Chibret)
Tecnolip(Tecnifar)

RussianFederation Apextatin(Kanonfarma)
Cardiostatin(MakizPharma)
Holetar(KRKA)
Lovasterol(Polpharma)
Medostatin(Medochemie)
Mevacor(MSD)
Rovacor(Ranbaxy)

Singapore Ellanco(Duopharma)
Elstatin(Glenmark)
Lochol(Micro)
Lofacol(Dexa)
Lostatin(Reddy)
Lovastin(YungShin)
Medostatin(Medochemie)
Mevacor(MSD)
Rovacor(Ranbaxy)

SouthAfrica Lovachol(Aspen)

Spain Aterkey(Pharminicio)
Colesvir(Vir)
 Lipofren(Abello)
Liposcler(UCB)
Mevacor(MSD)
Mevasterol(Cantabria)
Nergadan(Vifor)
Taucor(SigmaTau)

Venezuela Dislipin(Leti)
Levistan(Giempi)
Lostatin(Biofarma)
Lovanil(Flupal)
Lovas(RoemmersKlinos)
Mevacor(MSD)

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