Indomethacin - Drug Information

6/9/2016
Indomethacin:Druginformation
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Copyright19782016Lexicomp,Inc.Allrightsreserved.
(Foradditionalinformationsee"Indomethacin:Patientdruginformation"andsee"Indomethacin:Pediatricdrug
information")
ForabbreviationsandsymbolsthatmaybeusedinLexicomp(showtable)
ALERT:USBoxedWarning
Seriouscardiovascularthromboticevents:
Nonsteroidalantiinflammatorydrugs(NSAIDs)causeanincreasedriskofseriouscardiovascularthromboticevents,
includingmyocardialinfarction(MI)andstroke,whichcanbefatal.Thisriskmayoccurearlyintreatmentandmay
increasewithdurationofuse.
Indomethaciniscontraindicatedinthesettingofcoronaryarterybypassgraft(CABG)surgery.
Seriousgastrointestinalbleeding,ulceration,andperforation:
NSAIDscauseanincreasedriskofseriousgastrointestinal(GI)adverseeventsincludingbleeding,ulceration,and
perforationofthestomachorintestines,whichcanbefatal.Theseeventscanoccuratanytimeduringuseand
withoutwarningsymptoms.Elderlypatientsandpatientswithapriorhistoryofpepticulcerdiseaseand/orGIbleeding
areatgreaterriskforseriousGIevents.
BrandNames:US IndocinTivorbex
BrandNames:Canada NovoMethacinProIndoratioIndomethacinSandozIndomethacin
PharmacologicCategory Analgesic,NonopioidNonsteroidalAntiinflammatoryDrug(NSAID),Oral
NonsteroidalAntiinflammatoryDrug(NSAID),Parenteral
Dosing:Adult
Inflammatory/rheumatoiddisorders:Note:Uselowesteffectivedosefortheshortestdurationpossible.
Oral(immediaterelease[excludingTivorbex)]),rectal:25mg2to3timesdailyifwelltolerated,increasedailydosage
by 25 or 50 mg at weekly intervals until satisfactory response or a total daily dose of 150 to 200 mg/day
(maximum dose: 200 mg/day) is reached. In patients with arthritis and persistent night pain and/or morning
stiffnessmaygivethelargerportion(uptomaximumof100mg)ofthetotaldailydoseatbedtime.
Oral(extendedreleasecapsules):Initial:75mgoncedaily,mayincreaseto75mgtwicedaily(maximumdose:150
mg/day).
Bursitis/tendonitis of the shoulder: Oral (excluding Tivorbex and Canadian products), rectal (excluding Canadian
products):Initialdose:75to150mg/dayin3to4divideddosesor1to2divideddosesforextendedreleaseusual
treatmentis7to14daysdiscontinueaftersigns/symptomsofinflammationhavebeencontrolledforseveraldays.
Acutegoutyarthritis:Oral(excludingextendedreleasecapsulesandTivorbex),rectal:50mg3timesdailyuntilpainis
tolerablethenrapidlyreducedosetocompletecessationofdrug.
Acutepain(mildtomoderate):Oral(Tivorbexonly):20mg3timesdailyor40mg2or3timesdaily
Prevention of pancreatitis postendoscopic retrograde cholangiopancreatography (ERCP) (offlabel use): Rectal:
100mgimmediatelyafterERCP(Elmunzer,2012)
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Dosing:Pediatric
(Foradditionalinformationsee"Indomethacin:Pediatricdruginformation")
Patentductusarteriosus:
Neonates weighing between 500 to 1,750 g: IV: Initial: 0.2 mg/kg, followed by 2 doses depending on postnatal age
(PNA):
PNAattimeofFIRSTdose<48hours:0.1mg/kgat12to24hourintervals
PNAattimeofFIRSTdose2to7days:0.2mg/kgat12to24hourintervals
PNAattimeofFIRSTdose>7days:0.25mg/kgat12to24hourintervals
Note:Ingeneral,mayuse12hourdosingintervalifurineoutput>1mL/kg/hourafterpriordoseuse24hourdosing
interval if urine output is <1 mL/kg/hour but >0.6 mL/kg/hour. Doses should be withheld if patient has oliguria
(urineoutput<0.6mL/kg/hour)oranuriaatthescheduledtimeofthesecondorthirddosedonotgiveadditional
dosesuntilrenalfunctionhasreturnedtonormal.Iftheductusarteriosusclosesorissignificantlyreducedinsize
after 48 hours or more from completion of first course, no further doses are necessary. If the ductus arteriosus
reopens, a second course of 1 to 3 doses may be given if unresponsive after 2 doses, surgery may be
necessary.
Inflammatory/rheumatoid disorders: Note: Use lowest effective dose for the shortest duration possible. Canadian
labelingcontraindicatesuseinchildrenandadolescents<14years.
Children2years(limiteddataavailable):Oral(excludingextendedreleasecapsulesandTivorbex):1to2mg/kg/day
in2to4divideddosesmaximumdailydose:4mg/kg/dayor200mg/day,whicheverisless
Adolescents>14years:
Oral(immediaterelease[excludingTivorbex]),rectal:Refertoadultdosing.
Oral(extendedreleasecapsules):Refertoadultdosing.
Dosing:Geriatric Refertoadultdosing.Uselowestrecommendeddoseandfrequencyinelderlytoinitiatetherapy
forindicationslistedinadultdosing.
Dosing:RenalImpairment
USlabeling:
Oral/rectal:Therearenodosageadjustmentsprovidedinthemanufacturerslabelingnotrecommendedinpatients
withadvancedrenaldisease.
Injection:Ifanuriaormarkedoliguria(urinaryoutput<0.6mL/kg/hour)evidentatthescheduledtimeofthesecondor
thirddose,holddoseuntilrenalfunctionreturnstonormal.Useiscontraindicatedinneonateswithsignificant
renalimpairment.
Canadianlabeling:
Mildtomoderateimpairment:Therearenodosageadjustmentsprovidedinthemanufacturerslabelingusewith
cautionandconsiderlowerdoses.
Severeimpairment(CrCl<30mL/minute)ordeterioratingrenalfunction:Useiscontraindicated.
KDIGO2012guidelinesprovidethefollowingrecommendationsforNSAIDs:
eGFR30to<60mL/minute/1.73m2:Temporarilydiscontinueinpatientswithintercurrentdiseasethatincreasesrisk
ofacutekidneyinjury.
eGFR<30mL/minute/1.73m2:Avoiduse.
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Dosing:HepaticImpairment
USlabeling:Therearenodosageadjustmentsprovidedinthemanufacturerslabelingusewithcaution.
Canadianlabeling:Therearenodosageadjustmentsprovidedinthemanufacturerslabeling.Useiscontraindicatedin
severeliverimpairmentoractiveliverdisease.
DosageForms:US Excipientinformationpresentedwhenavailable(limited,particularlyforgenerics)consult
specificproductlabeling.[DSC]=Discontinuedproduct
Capsule,Oral:
Tivorbex:20mg,40mg[containsbrilliantbluefcf(fd&cblue#1),fd&cblue#2(indigotine),fd&cred#40]
Generic:25mg,50mg
CapsuleExtendedRelease,Oral:
Generic:75mg
SolutionReconstituted,Intravenous:
Indocin:1mg(1ea[DSC])
Generic:1mg(1ea)
SolutionReconstituted,Intravenous[preservativefree]:
Generic:1mg(1ea)
Suppository,Rectal:
Indocin:50mg(30ea)
Suspension,Oral:
Indocin:25mg/5mL(237mL)[containsalcohol,usppineapplecoconutmintflavor]
GenericEquivalentAvailable:US Maybeproductdependent
DosageForms:Canada Note:ReferalsotoDosageForms.Extendedreleasecapsule,intravenoussolution,
andoralsuspensionarenotavailableinCanada.
Excipientinformationpresentedwhenavailable(limited,particularlyforgenerics)consultspecificproductlabeling.
Suppository,Rectal:100mg
MedicationGuideand/orVaccineInformationStatement(VIS) AnFDAapprovedpatient
medicationguide,whichisavailablewiththeproductinformationandasfollows,mustbedispensedwiththismedication:
Indocin:http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088612.pdf
IndocinSR:http://www.fda.gov/downloads/Drugs/DrugSafety/UCM501640.pdf
Tivorbex::http://www.fda.gov/downloads/Drugs/DrugSafety/UCM501662.pdf
Administration
Oral: Administer with food, immediately after meals, or with milk or antacids to decrease GI adverse effects. Extended
releasecapsulesmustbeswallowedwholedonotcrush.
IV:Administerover20to30minutes.ReconstituteIVformulationjustpriortoadministrationdiscardanyunusedportion
avoidIVbolusadministrationorinfusionviaanumbilicalcatheterintovesselsnearthesuperiormesentericarteryas
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thesemaycausevasoconstrictionandcancompromisebloodflowtotheintestines.Donotadministerintraarterially.
Avoidextravascularinjectionorleakagesolutionmaybeirritatingtotissue.
Rectal:Forrectaluseonlynotfororalorintravaginaluse.
Compatibility StableinNS.
Ysiteadministration:
Compatible:Furosemide,insulin(regular),nitroprusside,potassiumchloride,sodiumbicarbonate.
Incompatible:Aminoacidinjection,calciumgluconate,cimetidine,dobutamine,dopamine,gentamicin,levofloxacin,
pantoprazole,tobramycin.Variable(consultdetailedreference):Dextroseinjection.
Compatibilityinsyringe:Incompatible:Pantoprazole.
Use
Acutepain,mildtomoderate(Tivorbexonly):Treatmentofmildtomoderateacutepaininadults.
Arthritis(excludingTivorbex):Treatmentofmoderatetosevererheumatoidarthritis(RA),includingacuteflaresof
chronicdiseasemoderatetosevereosteoarthritis(OA)acutegoutyarthritis(exceptextendedrelease[ER]
capsules).
Inflammatoryconditions(excludingTivorbex):Treatmentofmoderatetosevereankylosingspondylitisacutepainful
bursitisand/ortendinitisoftheshoulder(excludingCanadianproducts).
Patentductusarteriosus(IVonly):Tocloseahemodynamicallysignificantpatentductusarteriosusinprematureinfants
weighingbetween500and1,750gwhen48hoursusualmedicalmanagement(eg,fluidrestriction,diuretics,digitalis,
respiratorysupport)isineffective.
Use:OffLabel
PericarditisPreventionofpancreatitispostendoscopicretrogradecholangiopancreatography(ERCP)Managementof
pretermlabor
MedicationSafetyIssues
Soundalike/lookalikeissues:
IndocinmaybeconfusedwithImodium,Lincocin,Minocin,Vicodin
GeriatricPatients:HighRiskMedication:
BeersCriteria:IndomethacinisidentifiedintheBeersCriteriaasapotentiallyinappropriatemedicationtobeavoided
inpatients65yearsandolder(independentofdiagnosisorcondition)duetoanincreasedriskofNSAIDrelated
adverseeventsandadverseCNSeffectsinolderadultscomparedtootherNSAIDs(BeersCriteria[AGS2015]).
PharmacyQualityAlliance(PQA):Indomethacinisidentifiedasahighriskmedicationinpatients65yearsandolder
onthePQAs,UseofHighRiskMedicationsintheElderly(HRM)performancemeasure,asafetymeasureused
bytheCentersforMedicareandMedicaidServices(CMS)StarRatingSystemforMedicareplans.
AdverseReactionsSignificant
>10%:
Centralnervoussystem:Headache(12%to16%)
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Gastrointestinal:Vomiting(12%)
Hematologic&oncologic:Postoperativehemorrhage(11%)
1%to10%:
Cardiovascular:Presyncope(3%),syncope(2%)
Centralnervoussystem:Dizziness(3%to9%),depression(<3%),drowsiness(<3%),fatigue(<3%),malaise(<3%),
vertigo(<3%)
Dermatologic:Pruritus(1%to4%),hyperhidrosis(2%),skinrash(1%to2%)
Endocrine&metabolic:Hotflash(2%)
Gastrointestinal: Epigastric pain (3% to 9%), heartburn (3% to 9%), nausea (3% to 9%), dyspepsia (2% to 9%),
constipation (6%), diarrhea (3%), abdominal pain (<3%), decreased appetite (2%), rectal irritation
(suppository),tenesmus(suppository)
Otic:Tinnitus(<3%)
Miscellaneous:Swelling(3%postprocedural)
<1% (Limited to important or lifethreatening): Acute respiratory distress, agranulocytosis, anaphylaxis, anemia,
angioedema, aphthous stomatitis, aplastic anemia, aseptic meningitis, asthma, bone marrow depression, cardiac
arrhythmia,cardiacfailure,cerebrovascularaccident,chestpain,cholestaticjaundice,coma,confusion,convulsions,
cornealdeposits,depersonalization,depression,diplopia,disseminatedintravascularcoagulation,dysarthria,edema,
erythema multiforme, erythema nodosum, exacerbation of epilepsy, exacerbation of Parkinsons disease, exfoliative
dermatitis, fluid retention, gastritis, gastroenteritis, gastrointestinal hemorrhage, gastrointestinal perforation (rare),
gastrointestinal ulcer, glycosuria, gynecomastia, hearing loss, hematuria, hemodynamic deterioration (patients with
severe heart failure and hyponatremia), hemolytic anemia, hepatic failure, hepatic necrosis, hepatitis (including fatal
cases), hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperglycemia, hyperkalemia, hypersensitivity reaction,
hypertension, hypotension, immune thrombocytopenia, interstitial nephritis, intestinal obstruction, intestinal stenosis,
involuntary muscle movements, jaundice, leukopenia, maculopathy, myocardial infarction, necrotizing fasciitis,
nephrotic syndrome, oliguria, peripheral neuropathy, proctitis, psychosis, pulmonary edema, purpura, rectal
hemorrhage, regional ileitis, renal failure, renal insufficiency, retinal disturbance, shock, significant cardiovascular
event, StevensJohnson syndrome, stomatitis, syncope, thrombocytopenia, thrombophlebitis, toxic amblyopia, toxic
epidermalnecrolysis,ulcerativecolitis,vaginalhemorrhage
Contraindications
Hypersensitivity(eg,anaphylacticreactions,seriousskinreactions)toindomethacinoranycomponentoftheformulation
useinthesettingofcoronaryarterybypassgraft(CABG)surgeryhistoryofasthma,urticaria,orallergictype
reactionsaftertakingaspirinorotherNSAIDagentspatientswithahistoryofproctitisorrecentrectalbleeding
(suppositories).
Neonates(IVonly):Necrotizingenterocolitis(provenorsuspected)significantrenalimpairmentactivebleeding(including
intracranialhemorrhageandgastrointestinalbleeding),thrombocytopenia,coagulationdefectsuntreatedinfection
(provenorsuspected)congenitalheartdiseasewherepatencyoftheductusarteriosusisnecessaryforadequate
pulmonaryorsystemicbloodflow(eg,pulmonaryatresia,severetetralogyofFallot,severecoarctationoftheaorta)
Canadianlabeling:Additionalcontraindications(notinUSlabeling):Severeuncontrolledheartfailureknownhyperkalemia
activegastric/duodenal/pepticulceractiveGIbleedhistoryofrecurrentGIulcerationactiveGIinflammatory
diseasecerebrovascularbleedingorotherbleedingdisordersseverehepaticimpairmentoractiveliverdisease
severerenalimpairment(CrCl<30mL/minute)ordeterioratingrenalfunctionconcurrentusewithotherNSAIDs
completeorpartialsyndromeofnasalpolypschildrenandadolescents<14yearsofagebreastfeedingpregnancy
(thirdtrimester)
Warnings/Precautions
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Concernsrelatedtoadverseeffects:
Anaphylactoidreactions:Eveninpatientswithoutpriorexposureanaphylactoidreactionsmayoccurpatientswith
"aspirintriad"(bronchialasthma,aspirinintolerance,rhinitis)maybeatincreasedrisk.Contraindicatedinpatients
whoexperiencebronchospasm,asthma,rhinitis,orurticariawithNSAIDoraspirintherapy.
Cardiovascularevents:[USBoxedWarning]:NSAIDscauseanincreasedriskofserious(andpotentiallyfatal)
adversecardiovascularthromboticevents,includingMIandstroke.Riskmayoccurearlyduring
treatmentandmayincreasewithdurationofuse.Relativeriskappearstobesimilarinthosewithandwithout
knowncardiovasculardiseaseorriskfactorsforcardiovasculardiseasehowever,absoluteincidenceofserious
cardiovascularthromboticevents(whichmayoccurearlyduringtreatment)washigherinpatientswithknown
cardiovasculardiseaseorriskfactorsandinthosereceivinghigherdoses.Newonsethypertensionor
exacerbationofhypertensionmayoccur(NSAIDsmayalsoimpairresponsetoACEinhibitors,thiazidediuretics,
orloopdiuretics)maycontributetocardiovasculareventsmonitorbloodpressureusewithcautioninpatients
withhypertension.Maycausesodiumandfluidretention,usewithcautioninpatientswithedema.Avoidusein
heartfailure(ACCF/AHA[Yancy2013]).AvoiduseinpatientswithrecentMIunlessbenefitsoutweighriskof
cardiovascularthromboticevents.Usethelowesteffectivedosefortheshortestdurationoftime,consistentwith
individualpatientgoals,toreduceriskofcardiovasculareventsalternatetherapiesshouldbeconsideredfor
patientsathighrisk.
CNSeffects:Maycausedrowsiness,dizziness,blurredvision,andotherneurologiceffectswhichmayimpair
physicalormentalabilitiespatientsmustbecautionedaboutperformingtaskswhichrequirementalalertness
(eg,operatingmachineryordriving).Headachemayoccurcessationoftherapyrequiredifheadachepersists
afterdosagereduction.
Gastrointestinalevents:[USBoxedWarning]:NSAIDscauseincreasedriskofseriousgastrointestinal
inflammation,ulceration,bleeding,andperforation(maybefatal)elderlypatientsandpatientswith
historyofpepticulcerdiseaseand/orGIbleedingareatgreaterriskforseriousGIevents.Theseevents
mayoccuratanytimeduringtherapyandwithoutwarning.AvoiduseinpatientswithactiveGIbleeding.
UsecautionwithahistoryofGIulcers,concurrenttherapyknowntoincreasetheriskofGIbleeding(eg,aspirin,
anticoagulantsand/orcorticosteroids,selectiveserotoninreuptakeinhibitors),advancedhepaticdisease,
coagulopathy,smoking,useofalcohol,orintheelderlyordebilitatedpatients.Usethelowesteffectivedosefor
theshortestdurationoftime,consistentwithindividualpatientgoals,toreduceriskofGIadverseevents
alternatetherapiesshouldbeconsideredforpatientsathighrisk.Whenusedconcomitantlywithaspirin,a
substantialincreaseintheriskofgastrointestinalcomplications(eg,ulcer)occursconcomitantgastroprotective
therapy(eg,protonpumpinhibitors)isrecommended(Bhatt2008).
Hematologiceffects:Plateletadhesionandaggregationmaybedecreasedmayprolongbleedingtimepatientswith
coagulationdisordersorwhoarereceivinganticoagulantsshouldbemonitoredclosely.Anemiamayoccur
patientsonlongtermNSAIDtherapyshouldbemonitoredforanemia.Rarely,NSAIDusehasbeenassociated
withpotentiallysevereblooddyscrasias(eg,agranulocytosis,thrombocytopenia,aplasticanemia).
Hepaticeffects:Transaminaseelevationshavebeenreportedwithusecloselymonitorpatientswithanyabnormal
liverfunctiontest(LFT).Rare,sometimesfatalseverehepaticreactions(eg,fulminanthepatitis,hepatic
necrosis,hepaticfailure)haveoccurredwithNSAIDusediscontinueimmediatelyifclinicalsignsorsymptoms
ofliverdiseasedeveloporifsystemicmanifestationsoccur.
Hyperkalemia:NSAIDusemayincreasetheriskofhyperkalemia,particularlyintheelderly,diabetics,renal
disease,andwithconcomitantuseofotheragentscapableofinducinghyperkalemia(eg,ACEinhibitors).
Monitorpotassiumclosely.
Ophthalmiceffects:Prolongedtherapymaycausecornealdepositsandretinaldisturbances,includingthoseofthe
macula.Discontinueusewithblurredordiminishedvisionandperformophthalmologicexam.Periodically
evaluatevisioninallpatientsreceivinglongtermtherapy.
Renaleffects:NSAIDusemaycompromiseexistingrenalfunctiondosedependentdecreasesinprostaglandin
synthesismayresultfromNSAIDuse,reducingrenalbloodflowwhichmaycauserenaldecompensation
(usuallyreversible).Patientswithimpairedrenalfunction,dehydration,hypovolemia,heartfailure,hepatic
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impairment,thosetakingdiuretics,andACEinhibitors,andtheelderlyareatgreaterriskofrenaltoxicity.
Rehydratepatientbeforestartingtherapymonitorrenalfunctionclosely.LongtermNSAIDusemayresultin
renalpapillarynecrosisandotherrenalinjury.
Skinreactions:NSAIDsmaycausepotentiallyfatalseriousskinadverseeventsincludingexfoliativedermatitis,
StevensJohnsonsyndrome(SJS),andtoxicepidermalnecrolysis(TEN)mayoccurwithoutwarning
discontinueuseatfirstsignofskinrash(oranyotherhypersensitivity).
Diseaserelatedconcerns:
Asepticmeningitis:Mayincreasetheriskofasepticmeningitis,especiallyinpatientswithsystemiclupus
erythematosus(SLE)andmixedconnectivetissuedisorders.
Asthma:Contraindicatedinpatientswithaspirinsensitiveasthmasevereandpotentiallyfatalbronchospasmmay
occur.Usecautioninpatientswithotherformsofasthma.
Coronaryarterybypassgraftsurgery:[USBoxedWarning]:Useiscontraindicatedinthesettingofcoronary
arterybypassgraft(CABG)surgery.RiskofMIandstrokemaybeincreasedwithusefollowingCABGsurgery.
Depression:Usecautionwithdepressionusemayaggravatedepressionorotherpsychiatricdisorders.
Epilepsy:Usecautionwithepilepsyusemayaggravatethiscondition.
Hepaticimpairment:Usewithcautioninpatientswithhepaticimpairmentpatientswithadvancedhepaticdisease
areatanincreasedriskofGIbleedingwithNSAIDs.Canadianlabelingcontraindicatesuseinseverehepatic
impairmentoractiveliverdisease.
Parkinsonism:UsecautionwithParkinsondiseaseusemayaggravatethiscondition.
Renalimpairment:Avoiduseinpatientswithadvancedrenaldiseasediscontinueusewithpersistentorworsening
abnormalrenalfunctiontests.Theinjectionformulationiscontraindicatedinneonateswithsignificantrenal
impairment.Canadianlabelingcontraindicatesuseinsevererenalimpairment(CrCl<30mL/minute)or
deterioratingrenalfunction.
Concurrentdrugtherapyissues:
Drugdruginteractions:Potentiallysignificantinteractionsmayexist,requiringdoseorfrequencyadjustment,
additionalmonitoring,and/orselectionofalternativetherapy.Consultdruginteractionsdatabaseformoredetailed
information.
Specialpopulations:
Elderly:ElderlypatientsareatgreaterriskforseriousGI,cardiovascular,and/orrenaladverseeventsusewith
caution.Indomethacinmaycauseconfusionor,rarely,psychosisremainalerttothepossibilityofsuchadverse
reactionsinelderlypatients.
Pediatric:Oral:Therehavebeencasesofhepatotoxicityreportedinpediatricpatientswithjuvenilerheumatoid
arthritis,includingfatalities.Closelymonitorifneededinpediatricpatients2yearsandperiodicallyassessliver
function.
Otherwarnings/precautions:
Appropriateuse:Tivorbexisnotindicatedforlongtermuse.
Surgical/dentalprocedures:Withholdforatleast4to6halflivespriortosurgicalordentalprocedures.
Metabolism/TransportEffects SubstrateofCYP2C19(minor),CYP2C9(minor)Note:Assignmentof
Major/MinorsubstratestatusbasedonclinicallyrelevantdruginteractionpotentialInhibitsCYP2C19(weak),CYP2C9
(weak)
DrugInteractions
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(Foradditionalinformation:LaunchLexiInteractDrugInteractionsProgram)
5ASADerivatives:NonsteroidalAntiInflammatoryAgentsmayenhancethenephrotoxiceffectof5ASADerivatives.
RiskC:Monitortherapy
ACEInhibitors:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.Specifically,the
combinationmayresultinasignificantdecreaseinrenalfunction.NonsteroidalAntiInflammatoryAgentsmay
diminishtheantihypertensiveeffectofACEInhibitors.RiskC:Monitortherapy
AgentswithAntiplateletProperties(e.g.,P2Y12inhibitors,NSAIDs,SSRIs,etc.):Mayenhancetheantiplateleteffectof
otherAgentswithAntiplateletProperties.RiskC:Monitortherapy
Alcohol(Ethyl):Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.Specifically,theriskof
GIbleedingmaybeincreasedwiththiscombination.RiskC:Monitortherapy
Aliskiren:NonsteroidalAntiInflammatoryAgentsmaydiminishtheantihypertensiveeffectofAliskiren.NonsteroidalAnti
InflammatoryAgentsmayenhancethenephrotoxiceffectofAliskiren.Management:Monitorrenalfunction
periodicallyinpatientsreceivingaliskirenandanynonsteroidalantiinflammatoryagent.Patientsatelevatedriskof
renaldysfunctionincludethosewhoareelderly,arevolumedepleted,orhavepreexistingrenaldysfunction.RiskC:
Monitortherapy
Aminoglycosides:NonsteroidalAntiInflammatoryAgentsmaydecreasetheexcretionofAminoglycosides.Dataonlyin
prematureinfants.RiskC:Monitortherapy
AminolevulinicAcid:PhotosensitizingAgentsmayenhancethephotosensitizingeffectofAminolevulinicAcid.RiskC:
Monitortherapy
AngiotensinIIReceptorBlockers:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.
Specifically,thecombinationmayresultinasignificantdecreaseinrenalfunction.NonsteroidalAntiInflammatory
AgentsmaydiminishthetherapeuticeffectofAngiotensinIIReceptorBlockers.Thecombinationofthesetwoagents
mayalsosignificantlydecreaseglomerularfiltrationandrenalfunction.RiskC:Monitortherapy
Anticoagulants:AgentswithAntiplateletPropertiesmayenhancetheanticoagulanteffectofAnticoagulants.RiskC:
Monitortherapy
Anticoagulants:NonsteroidalAntiInflammatoryAgentsmayenhancetheanticoagulanteffectofAnticoagulants.RiskC:
Monitortherapy
Antidepressants(Tricyclic,TertiaryAmine):MayenhancetheantiplateleteffectofNSAID(Nonselective).RiskC:Monitor
therapy
Apixaban:NSAID(Nonselective)mayenhancetheadverse/toxiceffectofApixaban.Specifically,theriskofbleedingmay
beincreased.Management:Acomprehensiverisktobenefitassessmentshouldbedoneforallpatientsbeforeany
concurrentuseofapixabanandnonsteroidalantiinflammatorydrugs(NSAIDs).Ifcombined,monitorpatientsextra
closelyforsignsandsymptomsofbleeding.RiskD:Considertherapymodification
BetaBlockers:NonsteroidalAntiInflammatoryAgentsmaydiminishtheantihypertensiveeffectofBetaBlockers.
Exceptions:LevobunololMetipranolol.RiskC:Monitortherapy
BileAcidSequestrants:MaydecreasetheabsorptionofNonsteroidalAntiInflammatoryAgents.RiskD:Considertherapy
modification
BisphosphonateDerivatives:NonsteroidalAntiInflammatoryAgentsmayenhancetheadverse/toxiceffectof
BisphosphonateDerivatives.Bothanincreasedriskofgastrointestinalulcerationandanincreasedriskof
nephrotoxicityareofconcern.RiskC:Monitortherapy
Cephalothin:AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectofCephalothin.Specifically,the
riskforbleedingmaybeincreased.RiskC:Monitortherapy
Collagenase(Systemic):AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectofCollagenase
(Systemic).Specifically,theriskofinjectionsitebruisingand/orbleedingmaybeincreased.RiskC:Monitortherapy
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Corticosteroids(Systemic):Mayenhancetheadverse/toxiceffectofNSAID(Nonselective).RiskC:Monitortherapy
CycloSPORINE(Systemic):NonsteroidalAntiInflammatoryAgentsmayenhancethenephrotoxiceffectof
CycloSPORINE(Systemic).NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationof
CycloSPORINE(Systemic).CycloSPORINE(Systemic)mayincreasetheserumconcentrationofNonsteroidalAnti
InflammatoryAgents.Specifically,elevateddiclofenacconcentrationshavebeenreported.Management:Consider
alternativestononsteroidalantiinflammatoryagents(NSAIDs).Monitorforevidenceofnephrotoxicity,aswellas
increasedserumcyclosporineconcentrationsandsystemiceffects(e.g.,hypertension)duringconcomitanttherapy
withNSAIDs.RiskD:Considertherapymodification
DabigatranEtexilate:NSAID(Nonselective)mayenhancetheadverse/toxiceffectofDabigatranEtexilate.Specifically,
theriskofbleedingmaybeincreased.Management:Acomprehensiverisktobenefitassessmentshouldbedonefor
allpatientsbeforeanyconcurrentuseofdabigatranandnonsteroidalantiinflammatorydrugs(NSAIDs).Ifcombined,
monitorpatientsextracloselyforsignsandsymptomsofbleeding.RiskD:Considertherapymodification
Dasatinib:MayenhancetheanticoagulanteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
Deferasirox:NonsteroidalAntiInflammatoryAgentsmayenhancetheadverse/toxiceffectofDeferasirox.Specifically,the
riskforGIulceration/irritationorGIbleedingmaybeincreased.RiskC:Monitortherapy
DeoxycholicAcid:AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectofDeoxycholicAcid.
Specifically,theriskforbleedingorbruisinginthetreatmentareamaybeincreased.RiskC:Monitortherapy
Desmopressin:NonsteroidalAntiInflammatoryAgentsmayenhancetheadverse/toxiceffectofDesmopressin.RiskC:
Monitortherapy
Dexketoprofen:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoid
combination
Diclofenac(Systemic):Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.Management:
Seekalternativestothecombineduseofdiclofenacwithothernonsteroidalantiinflammatoryagents(NSAIDs).Avoid
theuseofdiclofenac/misoprostolwithotherNSAIDs.RiskD:Considertherapymodification
Digoxin:NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationofDigoxin.RiskC:Monitor
therapy
Drospirenone:NonsteroidalAntiInflammatoryAgentsmayenhancethehyperkalemiceffectofDrospirenone.RiskC:
Monitortherapy
Edoxaban:NSAID(Nonselective)mayenhancetheadverse/toxiceffectofEdoxaban.Specifically,theriskofbleeding
maybeincreased.Management:Acomprehensiverisktobenefitassessmentshouldbedoneforallpatientsbefore
anyconcurrentuseofedoxabanandnonsteroidalantiinflammatorydrugs(NSAIDs).Ifcombined,monitorpatients
extracloselyforsignsandsymptomsofbleeding.RiskD:Considertherapymodification
Eplerenone:NonsteroidalAntiInflammatoryAgentsmaydiminishtheantihypertensiveeffectofEplerenone.Nonsteroidal
AntiInflammatoryAgentsmayenhancethehyperkalemiceffectofEplerenone.RiskC:Monitortherapy
Floctafenine:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoidcombination
Glucagon:IndomethacinmaydiminishthetherapeuticeffectofGlucagon.RiskC:Monitortherapy
Glucosamine:MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
Haloperidol:NonsteroidalAntiInflammatoryAgentsmayenhancetheadverse/toxiceffectofHaloperidol.Specifically
includingdrowsinessandconfusion.RiskC:Monitortherapy
Herbs(Anticoagulant/AntiplateletProperties)(eg,Alfalfa,Anise,Bilberry):Mayenhancetheadverse/toxiceffectofAgents
withAntiplateletProperties.Bleedingmayoccur.RiskD:Considertherapymodification
Herbs(Anticoagulant/AntiplateletProperties)(eg,Alfalfa,Anise,Bilberry):Mayenhancetheadverse/toxiceffectof
NonsteroidalAntiInflammatoryAgents.Bleedingmayoccur.Management:Concomitanttreatmentwiththeseagents
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shouldgenerallybeavoided.Ifusedconcomitantly,increaseddiligenceinmonitoringforadverseeffects(eg,bleeding,
bruising,alteredmentalstatusduetoCNSbleeds)mustbeemployed.RiskD:Considertherapymodification
HydrALAZINE:NonsteroidalAntiInflammatoryAgentsmaydiminishtheantihypertensiveeffectofHydrALAZINE.RiskC:
Monitortherapy
Ibritumomab:AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectofIbritumomab.Bothagentsmay
contributetoimpairedplateletfunctionandanincreasedriskofbleeding.RiskC:Monitortherapy
Ibrutinib:Mayenhancetheadverse/toxiceffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
Ketorolac(Nasal):Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoid
combination
Ketorolac(Systemic):Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoid
combination
Limaprost:MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
Lithium:NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationofLithium.RiskD:Consider
therapymodification
LoopDiuretics:NonsteroidalAntiInflammatoryAgentsmaydiminishthediureticeffectofLoopDiuretics.LoopDiuretics
mayenhancethenephrotoxiceffectofNonsteroidalAntiInflammatoryAgents.Management:Monitorforevidenceof
kidneyinjuryordecreasedtherapeuticeffectsofloopdiureticswithconcurrentuseofanNSAID.Consideravoiding
concurrentuseinCHForcirrhosis.Concomitantuseofbumetanidewithindomethacinisnotrecommended.RiskD:
Considertherapymodification
Methotrexate:NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationofMethotrexate.
Management:Alternativeantiinflammatorytherapyshouldbeconsideredwheneverpossible,especiallyifthepatient
isreceivinghigher,antineoplasticdosesofmethotrexate.RiskD:Considertherapymodification
Morniflumate:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoidcombination
Multivitamins/Fluoride(withADE):MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:
Monitortherapy
Multivitamins/Minerals(withADEK,Folate,Iron):MayenhancetheantiplateleteffectofAgentswithAntiplatelet
Properties.RiskC:Monitortherapy
Multivitamins/Minerals(withAE,NoIron):MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.Risk
C:Monitortherapy
Naftazone:MayenhancetheantiplateleteffectofNonsteroidalAntiInflammatoryAgents.RiskC:Monitortherapy
NonsteroidalAntiInflammatoryAgents:Mayenhancetheadverse/toxiceffectofotherNonsteroidalAntiInflammatory
Agents.RiskC:Monitortherapy
NSAID(COX2Inhibitor):NonsteroidalAntiInflammatoryAgentsmayenhancetheadverse/toxiceffectofNSAID(COX2
Inhibitor).RiskX:Avoidcombination
Obinutuzumab:AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectofObinutuzumab.Specifically,
theriskofseriousbleedingrelatedeventsmaybeincreased.RiskC:Monitortherapy
Omacetaxine:NonsteroidalAntiInflammatoryAgentsmayenhancetheadverse/toxiceffectofOmacetaxine.Specifically,
theriskforbleedingrelatedeventsmaybeincreased.Management:Avoidconcurrentuseofnonsteroidal
antiinflammatorydrugs(NSAIDs)withomacetaxineinpatientswithaplateletcountoflessthan50,000/uL.RiskX:
Avoidcombination
Omega3FattyAcids:MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
Pelubiprofen:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoidcombination
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PEMEtrexed:NSAID(Nonselective)mayincreasetheserumconcentrationofPEMEtrexed.Management:Patientswith
mildtomoderaterenalinsufficiency(estimatedcreatinineclearance4579mL/min)shouldavoidNSAIDsfor25days
priorto,thedayof,and2daysafterpemetrexed.RiskD:Considertherapymodification
PentosanPolysulfateSodium:Mayenhancetheadverse/toxiceffectofAgentswithAntiplateletProperties.Specifically,
theriskofbleedingmaybeincreasedbyconcurrentuseoftheseagents.RiskC:Monitortherapy
Pentoxifylline:MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
Porfimer:PhotosensitizingAgentsmayenhancethephotosensitizingeffectofPorfimer.RiskC:Monitortherapy
PotassiumSparingDiuretics:NonsteroidalAntiInflammatoryAgentsmaydiminishtheantihypertensiveeffectof
PotassiumSparingDiuretics.NonsteroidalAntiInflammatoryAgentsmayenhancethehyperkalemiceffectof
PotassiumSparingDiuretics.RiskC:Monitortherapy
PRALAtrexate:NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationofPRALAtrexate.More
specifically,NSAIDSmaydecreasetherenalexcretionofpralatrexate.Management:Closelymonitorforincreased
pralatrexateserumlevelsand/ortoxicityifusedconcomitantlywithanNSAID.Monitorfordecreasedpralatrexate
serumlevelswithNSAIDdiscontinuation.RiskC:Monitortherapy
Probenecid:MayincreasetheserumconcentrationofNonsteroidalAntiInflammatoryAgents.RiskC:Monitortherapy
ProstacyclinAnalogues:MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitor
therapy
Prostaglandins(Ophthalmic):NonsteroidalAntiInflammatoryAgentsmaydiminishthetherapeuticeffectofProstaglandins
(Ophthalmic).NonsteroidalAntiInflammatoryAgentsmayalsoenhancethetherapeuticeffectsofProstaglandins
(Ophthalmic).RiskC:Monitortherapy
QuinoloneAntibiotics:NonsteroidalAntiInflammatoryAgentsmayenhancetheneuroexcitatoryand/orseizurepotentiating
effectofQuinoloneAntibiotics.NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationof
QuinoloneAntibiotics.RiskC:Monitortherapy
Rivaroxaban:NSAID(Nonselective)mayenhancetheadverse/toxiceffectofRivaroxaban.Specifically,theriskof
bleedingmaybeincreased.Management:Acomprehensiverisktobenefitassessmentshouldbedoneforallpatients
beforeanyconcurrentuseofrivaroxabanandnonsteroidalantiinflammatorydrugs(NSAIDs).Ifcombined,monitor
patientsextracloselyforsignsandsymptomsofbleeding.RiskD:Considertherapymodification
Salicylates:NSAID(Nonselective)mayenhancetheadverse/toxiceffectofSalicylates.Anincreasedriskofbleeding
maybeassociatedwithuseofthiscombination.NSAID(Nonselective)maydiminishthecardioprotectiveeffectof
Salicylates.SalicylatesmaydecreasetheserumconcentrationofNSAID(Nonselective).Exceptions:Choline
MagnesiumTrisalicylate.RiskD:Considertherapymodification
Salicylates:AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectofSalicylates.Increasedriskof
bleedingmayresult.RiskC:Monitortherapy
SelectiveSerotoninReuptakeInhibitors:MayenhancetheantiplateleteffectofNSAID(Nonselective).NSAID
(Nonselective)maydiminishthetherapeuticeffectofSelectiveSerotoninReuptakeInhibitors.Management:Consider
usingalternativeanalgesics,whenappropriate,and/oradditionofagastroprotectiveagent.Monitorpatientscloselyfor
signs/symptomsofbleeding,andforevidenceofdiminishedSSRIeffectivenesswithconcurrentuse.RiskD:
Considertherapymodification
Serotonin/NorepinephrineReuptakeInhibitors:MayenhancetheantiplateleteffectofNSAID(Nonselective).RiskC:
Monitortherapy
SodiumPhosphates:MayenhancethenephrotoxiceffectofNonsteroidalAntiInflammatoryAgents.Specifically,therisk
ofacutephosphatenephropathymaybeenhanced.Management:Consideravoidingthiscombinationbytemporarily
suspendingtreatmentwithNSAIDs,orseekingalternativestooralsodiumphosphatebowelpreparation.Ifthe
combinationcannotbeavoided,maintainadequatehydrationandmonitorrenalfunctionclosely.RiskD:Consider
therapymodification
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Tacrolimus(Systemic):NonsteroidalAntiInflammatoryAgentsmayenhancethenephrotoxiceffectofTacrolimus
(Systemic).RiskC:Monitortherapy
Talniflumate:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoidcombination
TenofovirProducts:NonsteroidalAntiInflammatoryAgentsmayenhancethenephrotoxiceffectofTenofovirProducts.
Management:Seekalternativestothesecombinationswheneverpossible.Avoiduseoftenofovirwithmultiple
NSAIDsoranyNSAIDgivenatahighdose.RiskD:Considertherapymodification
Tenoxicam:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.RiskX:Avoidcombination
ThiazideandThiazideLikeDiuretics:MayenhancethenephrotoxiceffectofNonsteroidalAntiInflammatoryAgents.
NonsteroidalAntiInflammatoryAgentsmaydiminishthetherapeuticeffectofThiazideandThiazideLikeDiuretics.
ThrombolyticAgents:AgentswithAntiplateletPropertiesmayenhancetheanticoagulanteffectofThrombolyticAgents.
Tiludronate:IndomethacinmayincreasetheserumconcentrationofTiludronate.Management:Separatedosesof
tiludronateatleasttwohoursbeforeortwohoursafterindomethacin.RiskD:Considertherapymodification
Tipranavir:MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
TositumomabandIodineI131Tositumomab:AgentswithAntiplateletPropertiesmayenhancetheadverse/toxiceffectof
TositumomabandIodineI131Tositumomab.Specifically,theriskofbleedingrelatedadverseeventsmaybe
increased.RiskC:Monitortherapy
Treprostinil:Mayenhancetheadverse/toxiceffectofNonsteroidalAntiInflammatoryAgents.Bleedingmayoccur.RiskC:
Monitortherapy
Triamterene:IndomethacinmayenhancethenephrotoxiceffectofTriamterene.Management:Consideralternativesto
concomitanttreatmentwithtriamtereneandindomethacin.Ifthecombinationcannotbeavoided,monitorfor
developmentofrenalfailure.RiskD:Considertherapymodification
Urokinase:AgentswithAntiplateletPropertiesmayenhancetheanticoagulanteffectofUrokinase.RiskX:Avoid
combination
Vancomycin:NonsteroidalAntiInflammatoryAgentsmayincreasetheserumconcentrationofVancomycin.RiskC:
Monitortherapy
Verteporfin:PhotosensitizingAgentsmayenhancethephotosensitizingeffectofVerteporfin.RiskC:Monitortherapy
VitaminE(Systemic):MayenhancetheantiplateleteffectofAgentswithAntiplateletProperties.RiskC:Monitortherapy
VitaminKAntagonists(eg,warfarin):NSAID(Nonselective)mayenhancetheanticoagulanteffectofVitaminK
Antagonists.RiskD:Considertherapymodification
FoodInteractions Foodmaydecreasetheratebutnottheextentofabsorption.Indomethacinpeakserumlevels
maybedelayediftakenwithfood.Management:AdministerwithfoodormilktominimizeGIupset.
PregnancyRiskFactor C(<30weeksgestation)C/D(30weeksgestation[manufacturerspecific])(show
table)
PregnancyImplications Adverseeventshavebeenobservedinanimalreproductionstudiesstudiesinpregnant
womenhavedemonstratedrisktothefetusifadministeredat30weeksgestation.Indomethacincrossestheplacenta
andcanbedetectedinfetalplasmaandamnioticfluid.Indomethacinexposureduringthefirsttrimesterisnotstrongly
associatedwithcongenitalmalformationshowever,cardiovascularanomaliesandcleftpalatehavebeenobserved
followingNSAIDexposureinsomestudies.TheuseofanNSAIDclosetoconceptionmaybeassociatedwithan
increasedriskofmiscarriage.NonteratogeniceffectshavebeenobservedfollowingNSAIDadministrationduringthethird
trimester,includingmyocardialdegenerativechanges,prenatalconstrictionoftheductusarteriosus,failureoftheductus
arteriosustoclosepostnatally,andfetaltricuspidregurgitationrenaldysfunctionorfailure,oligohydramnios
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gastrointestinalbleedingorperforation,increasedriskofnecrotizingenterocolitisintracranialbleeding(including
intraventricularhemorrhage),plateletdysfunctionwithresultantbleedingandpulmonaryhypertension.Theriskoffetal
ductalconstrictionfollowingmaternaluseofindomethacinisincreasedwithgestationalageanddurationoftherapy.
Becausetheymaycauseprematureclosureoftheductusarteriosus,useofNSAIDslateinpregnancyshouldbeavoided
(useafter31or32weeksgestationisnotrecommendedbysomeclinicians).Indomethacinhasbeenusedforashort
duration(eg,48hours)inthemanagementofpretermlabor.Indomethacinshouldbeusedwithcautioninpregnant
womenwithhypertension.ThechronicuseofNSAIDsinwomenofreproductiveagemaybeassociatedwithinfertility
thatisreversibleupondiscontinuationofthemedication.Useduringpregnancy(thirdtrimester)iscontraindicatedinthe
Canadianlabeling.
BreastFeedingConsiderations Indomethacinisexcretedintobreastmilkandlowamountshavebeen
measuredintheplasmaofnursinginfants.Seizuresinanursinginfantwereobservedinonecasereport,although
adverseeventshavenotbeennotedinothercases.Breastfeedingisnotrecommendedbymostmanufacturers(useis
contraindicatedintheCanadianlabeling)Tivorbexmaybeusedwithcautionduringbreastfeeding.(Thetherapeuticuse
ofindomethaciniscontraindicatedinneonateswithsignificantrenalfailure.)Hypertensivecrisisandpsychiatricside
effectshavebeennotedincasereportsfollowinguseofindomethacinforanalgesiainpostpartumwomen.Usewith
cautioninnursingwomenwithhypertensivedisordersofpregnancyorpreexistingrenaldisease.
DietaryConsiderations MaycauseGIupsettakewithfoodormilktominimize
Pricing:US
Capsule,controlledrelease(IndomethacinEROral)
75mg(60):$180.22
Capsules(IndomethacinOral)
25mg(100):$38.20
50mg(100):$63.75
Capsules(TivorbexOral)
20mg(90):$414.72
40mg(90):$414.72
Solution(reconstituted)(IndomethacinSodiumIntravenous)
1mg(1):$475.20
Suppository(IndocinRectal)
50mg(30):$603.00
Suspension(IndocinOral)
25mg/5mL(237mL):$533.26
Disclaimer:ThepricingdataprovidearepresentativeAWPand/orAAWPpricefromasinglemanufacturerofthebrand
and/orgenericproduct,respectively.Thepricingdatashouldbeusedforbenchmarkingpurposesonly,andassuchshould
notbeusedtosetoradjudicateanypricesforreimbursementorpurchasingfunctions.Pricingdataisupdatedmonthly.
MonitoringParameters Monitorresponse(pain,rangeofmotion,gripstrength,mobility,ADLfunction),
inflammationobserveforweightgain,edemamonitorrenalfunction(urineoutput,serumcreatinine,BUN)observefor
bleeding,bruisingevaluategastrointestinaleffects(abdominalpain,bleeding,dyspepsia)mentalconfusion,disorientation,
CBC,bloodpressure,liverfunctiontests(particularlywithpediatricuse)periodicophthalmologicexamswithprolonged
therapy
InternationalBrandNames AdcoIndogel(ZW)Agilex(AR)AmunoRetard(DE)Andocit(TH)Anodyne(TW)
Antalgin(MX)Argilex(AR)Arthrexin(AU,ZA,ZW)ArtrilonaS(UY)Artrinovo(ES)Catlep(JP)ChronoIndocid(FR)
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Confortid(AE,BH,CY,DK,EG,FI,IQ,IR,IS,JO,KW,LB,LY,OM,QA,SA,SE,SY,YE)Docin(TH)Ekmetacin(PT)
ElmegoSpray(TH)Elmetacin(AE,AU,BH,CZ,EC,EE,HU,KW,LT,LV,PK,PL,QA,SA,SK,VE)Flamaret(ZA)
IDC(TH)Idicin(IN)Idomethine(JP)IM75(AR)Imet(BF,BJ,CI,ET,GH,GM,GN,KE,LR,MA,ML,MR,MU,MW,
NE,NG,SC,SD,SL,SN,TN,TZ,UG,ZM,ZW)Inacid(ES)Indacin(PK)Indaflex(MX)Indalgin(TW)Indanet(MX)
Indecin(TW)Indo(SG)Indobene(CZ,HU,SK)Indocap(BD,IN,PK)IndocapS.R.(IN)Indocid(AE,AT,AU,BB,BF,
BH,BJ,BR,BS,BZ,CH,CI,CY,EG,ET,FR,GB,GH,GM,GN,GR,IQ,IR,JM,JO,KE,KW,LB,LR,LY,MA,ML,
MR,MU,MW,MX,NE,NG,OM,PE,PT,QA,SA,SC,SD,SL,SN,SY,TN,TT,TZ,UG,VE,YE,ZM,ZW)IndocidR
(NZ)Indocin(BM)IndocinI.V.(IL,KR)Indocolir(DE,TR)Indocollirio(IT)Indocollyre(AT,BE,CZ,FR,HR,HU,IL,
JO,KR,LB,NL,PL,PT,RU)IndoflamEye(IN)Indogesic(AE,BH,CY,EG,IQ,IR,JO,KW,LB,LY,OM,QA,SA,SY,
YE)Indol(LK)Indolag(AE,BF,BH,BJ,BM,CI,CY,EG,ET,GH,GM,GN,GY,IQ,IR,JO,KE,KW,LB,LR,LY,MA,
ML,MR,MU,MW,NE,NG,OM,PR,QA,SA,SC,SD,SL,SN,SR,SY,TN,TZ,UG,YE,ZM,ZW)Indolgina(CR,DO,
GT,HN,NI,PA,SV)Indomecin(CO)IndomedF(TH)Indomee(SE)Indomen(MY,SG)Indomet(AR,EE)Indometa
(KR)Indomin(AE,BH,CY,EG,IQ,IR,JO,KW,LB,LY,OM,QA,RU,SA,SY,YE)Indono(TH)Indorem(BM,GY,PR,
SR)Indosan(AE,BH,CY,EG,IQ,IR,JO,KW,LB,LY,OM,QA,SA,SY,YE)Indosima(PY)IndosinGel(HR)Indovis
(IL)Indoxen(HK)Indoy(TW)Indozu(TW)Indylon(BF,BJ,CI,ET,GH,GM,GN,KE,LR,MA,ML,MR,MU,MW,NE,
NG,SC,SD,SL,SN,TN,TZ,UG,ZM,ZW)Inomet(TR)Insaid(BD)LuQi(CN)Malival(MX)Metacen(IT)Methacin
(HK,LK)Metindol(PL)Mobilat(DE)Moviflex(PE)Omexin(BD)Paragan(BD)Rakev(LK)Recticin100(ET)
Reumacid(AE,BH,CY,EG,IQ,IR,JO,KW,LB,LY,OM,QA,SA,SY,YE)Reusin(ES)Rheumacid(BF,BJ,CI,ET,
GH,GM,GN,KE,LR,MA,ML,MR,MU,MW,NE,NG,SC,SD,SL,SN,TN,TZ,UG,ZM,ZW)Rindocin(BD)
Rothacin(AE)SchmerzSpray(DE)SigadocSpray(DE)Sportflex(BE)Stratasin(MX)Uniof(PE)ViGel(PH)Vindo
(LK)XantomicinForte(PY)
MechanismofAction Reversiblyinhibitscyclooxygenase1and2(COX1and2)enzymes,whichresultsin
decreasedformationofprostaglandinprecursorshasantipyretic,analgesic,andantiinflammatoryproperties
Otherproposedmechanismsnotfullyelucidated(andpossiblycontributingtotheantiinflammatoryeffecttovarying
degrees),includeinhibitingchemotaxis,alteringlymphocyteactivity,inhibitingneutrophilaggregation/activation,and
decreasingproinflammatorycytokinelevels.
PharmacodynamicsandPharmacokinetics
Onsetofaction:~30minutes
Duration:4to6hours
Absorption: Oral: Immediate release: Neonates: Formulation specific Adults: Prompt and extensive Extended release:
Adults: 90% over 12 hours (Note: 75 mg product is designed to initially release 25 mg and then 50 mg over an
extendedperiodoftime)
Distribution:CrossesbloodbrainbarrierNeonates:PDA:0.36L/kgPostPDAclosure:0.26L/kgAdults:0.341.57L/kg
Proteinbinding:99%
Metabolism: Hepatic significant enterohepatic recirculation metabolites include desmethyl, desbenzoyl and desmethyl
desbenzoyl(allinunconjugatedform)
Bioavailability:
Neonates, premature: Percent bioavailability reported in the literature is highly variable and may be influenced by
formulation components and indomethacin physicochemical properties (Scanlon 1982) some have suggested
that aqueous formulations are less bioavailable compared to ethanol based formulations (Mrongovious 1982
Scanlon 1982) aqueous suspension (in saline): 13% to 20% (Mrongovious 1982 Sharma 2003) ethanol based
(96%v/v)suspension:98.6%(AlZa'abi2007)
Adults:Oral:100%rectal:80%to90%(thanthatabsorbedfromcapsuleform)
Halflifeelimination:
Neonates:Postnatalage(PNA)<2weeks:20hoursPNA>2weeks:11hours
Adults:2.611.2hours7.6hours(Tivorbex)
Timetopeak:Oral:Immediaterelease:2hoursTivorbexcapsules:1.67hours
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Excretion:Urine(60%,primarilyasglucuronideconjugates)feces(33%,primarilyasmetabolites1.5%asunchanged
drug)
Clearance:Pretermneonates:~19mL/hour/kg(range:4.745.5mL/hour/kg)(AlZa'abi2007)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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