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eTherapeutics+Complete:TherapeuticChoices:Appendices:DosageAdjustmentinRenalImpairment

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Appendices:DosageAdjustmentinRenalImpairment
JamesMcCormack,BSc(Pharm),PharmD
BruceCarleton,BPharm,PharmD
PieraCalissi,BSc(Pharm),PharmD,FCSHP
DateofRevision:July2015

Introduction
Carefuldosageadjustmentmayreducetheriskofdrugtoxicityinpatientswithimpairedrenalfunction.Thefollowingis
anapproachtoempiricdosageadjustments(doseand/orinterval)inadultpatientsbasedonanestimateofrenalfunction
(Figure1,Table1).Thisapproachdoesnotapplytopatientsondialysis(consultspecializedreferences).

Patient/DrugConsiderations
Thefollowingquestionsshouldbeansweredpriortomakingempiricdosageadjustments.Table2providesdrugspecific
information.
Isthepatient'srenalfunctionimpaired?
Usethefollowingformula 1toestimatetheweightcorrectedcreatinineclearance(ClCr)andtoguideempiricdosage
adjustments:
Males:ClCr
(140age)1.5
(mL/s/70kg) =

serumcreatinine(mol/L)
Females:ClCr(mL/s/70kg)=0.85aboveequation
ManycliniciansmaybemorefamiliarwithaClCrformulathatincludesweight.WhenusingformulastoestimateClCr,first
identifythereasonfortheClCrdetermination.Ifanestimateofthepatient'strueClCr(inmL/second)isneeded,thenuse
aClCrformulathatincludesweight.However,iftheestimateofthedegreeofrenalimpairmentistoguidedosage
adjustments,useaweightcorrectedestimateofClCrratherthanthepatient'sactualClCr.Thisweightcorrectedestimate
isthencomparedtoanormalClCrfora70kgmale(1.82mL/s)toapproximatethedegreeofrenaldysfunction.
ChartsthatsuggestempiricdosageadjustmentsareusuallybasedontheassumptionthatthebaselineornormalClCris
1.82mL/s.Inaddition,aweightcorrectedClCriseasiertocalculate.
Elderly(>65years)ormalnourishedpatientsmayhaverelativelylowmusclemassandthereforeproducelesscreatinine.
Iftheactualserumcreatinineforsuchpatientsisused,theformulacanoftenoverestimaterenalfunction.Aruleof
thumbinsuchpatientsisnottouseaserumcreatinine<100mol/Lintheaboveformula.
Overthelastfewyears,anewequation(ModificationofDietinRenalDiseaseMDRD)toestimatetheglomerularfiltration
rate(GFR)hasfounditswayintoclinicaluse.TheMDRDisrecommendedforstagingchronickidneydiseasebecauseit
hasimprovedpredictiveperformanceovertheCockcroftGaultequationinestimatingtheGFR.Somecliniciansalsouse
theMDRDtoestimatetheGFRinordertoadjustmedicationdosesinpatientswithrenalimpairment.However,in
adjustingdrugdosesinpatientswithrenalimpairment,theimprovedaccuracyoftheMDRDequationtopredicttheGFR
willnot,inmostcases,resultinmeasurablyimprovedoutcomessuchasenhancedmedicationsafetyorefficacy.Thisis
becausemostrecommendationsfordrugdosinginpatientswithrenalimpairmentarenotbasedonspecific
pharmacokineticorpharmacodynamicoutcomedata.Instead,thedosagerecommendationsarebasedonsomewhat
broadandarbitraryGFRcutoffpoints.Giventhis,boththeCockcroft,GaultandMDRDequationsprovidesufficiently
accurateestimatesofrenalfunctionforuseindrugdosageadjustment.Cliniciansshouldlikelychoosetheequationthatis
easiesttouseortheonewithwhichtheyaremostfamiliar.Mostimportantly,cliniciansneedtodeterminerational
startingdosesusingnotonlytheseequations,butalsobasedontheurgencyoftheneedforaresponsetodrugtherapy.
Alltheseissuesmakethecurrentdebateaboutwhichformulatousetoestimaterenalfunctionsomewhatirrelevant.
However,regardlessofthemethodused,thereisacriticalnextstep:titratethedosewheneverpossible,anddetermine
thecorrectdosebymonitoringapatient'sresponsetothedosechosen.
Ingeneral,ifClCrestimatesare>1mL/s/70kg,empiricdosageadjustmentsarenotrequiredbecausechangesinClCr
from2to1mL/s/70kgareassociatedwithrelativelysmallchangesinthehalflifeofadrugoritsactivemetabolite.
However,asClCrfallsbelow1mL/s/70kg,empiricdosageadjustmentsshouldbebasedonthefollowingquestions.
Isthedrugeffective/safeinpatientswithrenalimpairment?
Somedrugsareineffectiveorpotentiallytoxicinpatientswithclinicallyimportantrenaldysfunction(ClCr<0.5mL/s/70
kg)andshouldbeavoided(seeTable2,Commentscolumn).
Isthedrugnephrotoxic?
Anumberofdrugshavethepotentialtoworsenrenalfunctionandanalternativenonnephrotoxicagentshouldbeusedif
possible(seeTable2,Commentscolumn).

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Isanimmediateclinicaleffectrequired?
Whenfailuretoelicitanimmediateresponse(e.g.,lifethreateningconditionsorseverepain)posesaclinicallyimportant
riskofmortalityormorbidity,drugdosingshouldbeaimedatobtainingatherapeuticresponsewithinminutesorhours
irrespectiveofrenalfunction.Inanattempttoachievearapidresponse,usualinitialdosesshouldbeused,followedby
empiricdosageadjustmentsoncethepatienthasresponded.
Ifanimmediateeffectisnotrequired,canthedosebetitrated?
Manyconditionsdonotrequireanimmediateormaximaleffect,anddosetitrationcanoftenbeusedtodeterminethe
lowesteffectivedose.Toidentifythecorrectdoseforanypatient,butparticularlyinpatientswithrenalimpairment,start
withalowdose(e.g.,onequarteroronehalfofthetypicallyrecommendeddose),andtitrateuptoaclinicaleffect.
Isthedrug>50%renallyeliminatedordoesithaveactiveortoxicmetabolites?
Drugsthatareprimarilyeliminatedbythekidney(>50%)requireempiricdosageadjustmentsbasedonanestimateof
renalfunction(Table2).Inaddition,somedrugsaremetabolizedtoactiveortoxicmetaboliteswhichmaybeexcretedby
thekidneyandmayneeddosageadjustments.Somedrugsshouldbeavoidedinpatientswithcompromisedrenal
functioniftoxicmetabolitescanaccumulate(e.g.,meperidine).

ApproachtoEmpiricDosageAdjustments
Whendosetitrationisnotpossibleordesired,baseempiricdosageadjustmentsonestimatesofrenalfunction.

IntervalversusDoseAdjustment
Fordrugsgivenintermittently,thedoseorthedosingintervalcanbeadjustedbasedonthedesiredgoal.Oftena
combinationofextendingtheintervalandreducingthedoseiseffectiveandconvenient.Iftheaimistoachievesteady
statemaximum/peakandminimum/troughconcentrations(e.g.,aminoglycosides)similartothoseseeninpatientswith
normalrenalfunction,extendtheintervalbetweendoses.Ifarelativelyconstantsteadystateconcentrationisdesired
(e.g.,antihypertensives),reducethedose.

DrugsEliminated75%bytheKidney
Table1providesguidelinesforthedosageofthesedrugs(Table2)basedontheusualdosinginterval.Forfrequently
administereddrugs(e.g.,Q4HQ12H),extendingtheintervalmaydecreasethecostofadministrationorimprove
adherence.

DrugsEliminated50to<75%bytheKidney
Thesedrugshaveaclinicallyimportantproportionofnonrenalclearance,therefore,empiricdosageadjustmentsare
generallynotrequireduntilrenalfunctionestimatesare<0.75mL/s/70kg(Table1,Table2).

DrugsEliminated<50%bytheKidney
Fordrugseliminated<50%bythekidney(Table2),empiricdosageadjustmentsaregenerallynotrequired,assuming
thedrughasnoactiveortoxicmetabolites.However,thesedrugsmayrequiredosageadjustmentinpatientswith
clinicallyimportantliverdysfunction.

DrugswithActiveorToxicMetabolites
Empiricdosageadjustmentsfordrugswithactiveortoxicmetaboliteswhicharedependentonrenaleliminationshouldbe
madeasthoughthedrugwere75100%renallyeliminated(Table2,Commentscolumn).

FurtherDosageAdjustmentsBasedonClinicalResponse
Alloftheaboverecommendationsareforempiricdosageadjustments,andfurtherdosagechangesmustalwaysbe
madebasedonapatientspecificassessmentofefficacyandtoxicity.Serumdrugconcentrationmonitoringmayguide
dosageadjustmentsforcertaindrugs(Table2,Commentscolumn).

Algorithm

Figure1:EmpiricDosageAdjustmentBasedonRenalFunction(Adults)
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aForexample,antihypertensives,antihyperglycemics,antidepressants.
Abbreviations: ClCr=creatinineclearance

DosageAdjustmentTables

Table1:SuggestedEmpiricDosageAdjustmentsinAdultsforDrugsPrimarilyRenallyEliminatedbasedonpercentage
renaleliminationandestimatedcreatinineclearance(normalClCr=2mL/s/70kg)
HowtoUseTable1:
1. Estimaterenalfunction(weightcorrectedCICr),e.g.,apatientwithanestimatedClCrof0.42mL/s/70kgis
receivingivampicillin.
2. Determinepercentagerenaleliminationofdrug(Table2),e.g.,ampicillinis75100%renallyeliminated,
accordingtoTable2.
3. Determinenormaldosinginterval,e.g.,usualdosingintervalforampicillinisQ6H.
4. Usingaboveinformation,determineempiricdosageadjustment,e.g.,thepatient'sClCrisbetween0.25and0.5
mL/s/70kg.Therefore,theempiricdosingadjustmentistoadministertheampicillinQ12H.

NormalDosingInterval

%Renal
Elimination
ofDrug:

75100%

5074%

Q4H

>1

>0.75

Estimated

0.51

0.330.75

Q8H

Q12H

Q24H

Noadjustment No
required
adjustment
required

No
adjustment
required

No
adjustment
required

Noadjustment
required

Q6H

Q12H

Q24H

Reducedose

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Q6H

Q8H

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ClCr
(mL/s/70
kg)

by25%a

0.250.5

0.160.33

Q8H

Q12H

Q24H

Q24Hand
reducedose
by25%a

Reducedose
by50%a

<0.25

<0.16

Q12H

Q24H

Q24Hand
reducedose
by25%a

Q24Hand
reducedose
by50%a

Reducedose
by75%a

aForcertaindrugs,decreasingthedoseisnotappropriate,oronemayneedtoextendinterval>Q24Hifavailabledosageformsdonot
permitspecificdosereductions.

Table2:DosageAdjustmentinRenalImpairmentAdults

%Renal
Elimination
Drug

<50b

50
74c 75c

Comments

5aminosalicylicacid

abacavir

abatacept

acarbose

acebutolol

acenocoumarol

acetaminophen

acetazolamide

acitretin

acyclovir

adalimumab

adefovirdipivoxil

Nephrotoxic.Activemetaboliteassume75%renalelimination
fordosageadjustment

adenosine

albendazole

alemtuzumab

alendronate

Avoidinsevererenalimpairment

alfacalcidol

alfuzosin

aliskiren

allopurinol

Activemetaboliteassume75%renaleliminationfordosage
adjustment

almotriptan

alogliptin

alprazolam

alprostadil

alteplase

aluminumsalts

Avoidinsevererenalimpairmentasmayaccumulate

amantadine

amikacin

Nephrotoxicmonitorserumdrugconcentrations

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Avoidineffectiveinsevererenalimpairment

Activemetabolite

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amiloride

Avoidinsevererenalimpairment

aminophylline

amiodarone

Activemetabolitebutnodosageadjustmentrequired

amitriptyline

Activemetabolitebutnodosageadjustmentrequired

amlodipine

amoxicillin

amoxicillin/clavulanate

amphetamine,mixedsalts

Activemetabolitebutnodosageadjustmentrequired

amphotericin

Nephrotoxic

ampicillin

anakinra

anidulafungin

apixaban

apremilast

aprepitant

aripiprazole

ASA

asenapine

atazanavir

atenolol

atomoxetine

atorvastatin

Activemetabolitebutnodosageadjustmentrequired

atovaquone

atropine

auranofin

Avoidnephrotoxic

azathioprine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

azilsartan

azithromycin

baclofen

belimumab

benazepril

benztropine

bezafibrate

Avoidinrenalimpairment

bisacodyl

Activemetabolitebutnodosageadjustmentrequired

bismuthsubsalicylate

bisoprolol

bivalirudin

boceprevir

brinzolamide

bromocriptine

brompheniramine

budesonide

Manufacturerrecommendsdosereductioninsevererenal
impairment

Nephrotoxic

Reducedoseinsevererenalimpairment

Eyedropscontraindicatedinsevererenalimpairment

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bumetanide

Largerdosesmayberequiredinsevererenalimpairment

buprenorphine

bupropion

Activemetaboliteassume75%renaleliminationfordosage
adjustment

buserelin

buspirone

butalbital

Activemetaboliteassume75%renaleliminationfordosage
adjustment

caffeine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

calcitonin

calcitriol

calciumsalts

canagliflozin

candesartan

captopril

carbamazepine

Activemetabolitebutnodosageadjustmentrequired

carvedilol

Activemetabolitebutnodosageadjustmentrequired

cascara

Routeofeliminationunknown

caspofungin

cefaclor

cefadroxil

cefazolin

cefepime

cefixime

cefotaxime

cefoxitin

cefprozil

ceftazidime

ceftriaxone

cefuroxime

celecoxib

cephalexin

certolizumabpegol

cetirizine

chloralhydrate

Avoid.Activemetaboliteassume75%renaleliminationfor
dosageadjustment

chlordiazepoxide

Activemetaboliteassume75%renaleliminationfordosage
adjustment

chloroquine

chlorpheniramine

chlorpromazine

Activemetabolitebutnodosageadjustmentrequired

chlorpropamide

Avoid.Activemetaboliteassume75%renaleliminationfor
dosageadjustment

chlorthalidone

AvoidineffectiveatlowClCr

Lesseffectiveinmoderateandineffectiveinsevererenal
impairment

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Nephrotoxic

Polyethyleneglycolcomponentrenallyeliminated

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chlorzoxazone

cidofovir

Avoidnephrotoxic.Activemetaboliteassume75%renal
eliminationfordosageadjustment

cilazapril

Activemetaboliteassume75%renaleliminationfordosage
adjustment

cimetidine

cinacalcet

ciprofloxacin

citalopram

clarithromycin

clindamycin

clobazam

clodronate

Avoidnephrotoxic

clomiphene

clomipramine

clonazepam

clonidine

clopidogrel

cloxacillin

clozapine

Activemetabolitebutnodosageadjustmentrequired

cobicistat

codeine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

colchicine

Avoidinrenalimpairment

cyclobenzaprine

cyclophosphamide

Activemetabolites.Dosageadjustmentrecommendedinsevere
renalimpairment

cyclosporine

Nephrotoxicmonitorserumdrugconcentrations

cyproheptadine

cyproteroneacetate

dabigatran

Contraindicatedinsevererenalimpairment

dalteparin

danazol

dantrolene

dapagliflozin

Contraindicatedinmoderatetosevererenalimpairment

dapsone

daptomycin

darbepoetinalfa

darifenacin

darunavir

deferoxamine

delavirdine

delta9
tetrahydrocannabinol/cannabidiol

denosumab

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Activemetabolitebutnodosageadjustmentrequired

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desipramine

Activemetabolitebutnodosageadjustmentrequired

desloratadine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

desmopressin

desvenlafaxine

ManufacturerrecommendsdosageadjustmentifClCr<0.5
mL/s,although<50%renalelimination

dexamethasone

dexbrompheniramine

dexlansoprazole

dexrazoxane

Reducedoseby50%inpatientswithmoderatetosevererenal
impairment

dextroamphetamine

Activemetabolitebutnodosageadjustmentrequired

dextromethorphan

Activemetaboliteassume75%renaleliminationfordosage
adjustment

diazepam

Activemetabolitebutnodosageadjustmentrequired

diclofenac

Nephrotoxic

dicyclomine

didanosine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

dienogest

diflunisal

Nephrotoxic

digoxin

Monitorserumconcentrations

dihydroergotamine

Activemetabolite

diltiazem

Activemetabolitebutnodosageadjustmentrequired

dimenhydrinate

dimethylfumarate

diphenhydramine

diphenoxylate

Activemetabolite

dipyridamole

divalproex

dobutamine

docusate

dofetilide

dolasetron

Activemetabolitebutnodosageadjustmentrequired.Avoidin
severerenalimpairment

dolutegravir

domperidone

donepezil

Activemetabolitebutnodosageadjustmentrequired

doxazosin

doxepin

Activemetabolitebutnodosageadjustmentrequired

doxycycline

doxylamine

dronabinol

dronedarone

droperidol

duloxetine

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dutasteride

efavirenz

eletriptan

elvitegravir

emtricitabine

enalapril

Activemetaboliteassume75%renaleliminationfordosage
adjustment

enfuvirtide

enoxaparin

entacapone

entecavir

eplerenone

UsecontraindicatedbymanufacturerifClCr<0.8mL/s

epoetinalfa

eprosartan

eptifibatide

Dosageadjustmentrecommendedforpatientswithrenal
impairment

ergotamine

Avoidinrenalimpairment

ertapenem

erythromycin

escitalopram

Activemetabolitebutnodosageadjustmentrequired

eslicarbazepine

esmolol

esomeprazole

estrogens

etanercept

ethacrynicacid

Avoidinsevererenalimpairment

ethambutol

ethopropazine

Routeofeliminationunknown

ethosuximide

etidronate

Nephrotoxic

etodolac

Nephrotoxic

etravirine

exenatide

Avoidinsevererenalimpairment

ezetimibe

famciclovir

Activemetaboliteassume75%renaleliminationfordosage
adjustment

famotidine

fampridine

UsecontraindicatedbymanufacturerifClCr<1mL/s

febuxostat

felodipine

fenofibrate

Activemetaboliteassume75%renaleliminationfordosage
adjustment

fentanyl

ferumoxytol

fesoterodine

Activemetabolite

fexofenadine

Activemetaboliteassume75%renaleliminationfordosage

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adjustment
fidaxomicin

filgrastim

finasteride

fingolimod

flecainide

Activemetaboliteassume75%renaleliminationfordosage
adjustment

fluconazole

flucytosine

fludrocortisone

flunarizine

fluoxetine

Activemetabolitebutnodosageadjustmentrequired

flupentixol

fluphenazine

flurazepam

Activemetabolitebutnodosageadjustmentrequired

flurbiprofen

Nephrotoxic

fluvastatin

fluvoxamine

folicacid

%renaleliminationincreasedwithlargedoses

fondaparinux

fosamprenavir

fosaprepitant

foscarnet

Avoidnephrotoxic

fosfomycin

fosinopril

Activemetabolitebutnodosageadjustmentrequired

frovatriptan

furosemide

Largerdosesmayberequiredinsevererenalimpairment

gabapentin

galantamine

ganciclovir

gemfibrozil

Activemetaboliteassume75%renaleliminationfordosage
adjustment

gentamicin

Nephrotoxicmonitorserumdrugconcentrations

glatiramer

gliclazide

glimepiride

Activemetaboliteassume75%renaleliminationfordosage
adjustment

glucosamine

glyburide

Avoid.Activemetabolitebutnodosageadjustmentrequired

glycopyrrolate

golimumab

goserelin

granisetron

guaifenesin

Routeofeliminationunknown

guanfacine

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haloperidol

heparin

hydralazine

hydrochlorothiazide

AvoidineffectiveatlowClCr

hydrocodone

Activemetaboliteassume75%renaleliminationfordosage
adjustment

hydrocortisone

hydromorphone

hydroxychloroquine

hydroxyzine

hyoscine

ibuprofen

Nephrotoxic

ibutilide

Activemetabolitebutnodosageadjustmentrequired

imipenem/cilastatin

imipramine

Activemetabolitebutnodosageadjustmentrequired

indapamide

AvoidineffectiveatlowClCr

indinavir

indomethacin

Nephrotoxic

infliximab

insulin

interferonalfa

interferonbeta

irbesartan

ironsalts

isoniazid

isosorbidedinitrateor5
mononitrate

Activemetabolitebutnodosageadjustmentrequired

isotretinoin

Avoidinrenalimpairment

itraconazole

ketoconazole

ketoprofen

Nephrotoxic

ketorolac

Nephrotoxic

ketotifen

labetalol

lacosamide

Manufacturerrecommendsamaximumdailydoseof300mgin
patientswithendstagerenaldisease

lamivudine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

lamotrigine

lanreotide

lansoprazole

leflunomide

leuprolide

levetiracetam

levodopa

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Activemetabolitebutnodosageadjustmentrequired

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levofloxacin

levonorgestrel

levothyroxine

lidocaine

linagliptin

linezolid

liothyronine

liraglutide

lisdexamfetamine

lisinopril

lithium

loperamide

lopinavir/ritonavir

loratadine

lorazepam

losartan

lovastatin

loxapine

lurasidone

Activemetaboliteassume75%renaleliminationfordosage
adjustment

magnesiumsalts

Avoidinsevererenalimpairmentasmayaccumulate

maprotiline

Activemetabolitebutnodosageadjustmentrequired

maraviroc

ModifydosewhentakingconcurrentpotentCYP3A4inhibitors

medroxyprogesterone

mefenamicacid

mefloquine

megestrol

meloxicam

Nephrotoxic

memantine

meperidine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

mercaptopurine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

meropenem

mesna

metformin

methadone

methazolamide

Avoidineffectiveinsevererenalimpairment

methimazole

methocarbamol

methotrexate

Avoidnephrotoxic

methotrimeprazine

Activemetabolitebutnodosageadjustmentrequired

methoxsalen

methyldopa

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Activemetabolitebutnodosageadjustmentrequired

Nodataonrenalelimination

Nephrotoxicmonitorserumdrugconcentrations

Activemetabolite.Considerdosageadjustmentinsevererenal
impairment

Activemetabolitebutnodosageadjustmentrequired

Nephrotoxic

Avoidinsevererenalimpairment

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methylnaltrexone

methylphenidate

methylprednisolone

metoclopramide

Activemetabolitesassume75%renaleliminationfordosage
adjustment

metolazone

Dosagereductionnotnecessaryinrenalimpairment

metoprolol

metronidazole

Activemetabolitebutnodosageadjustmentrequired

mexiletine

Activemetabolitebutnodosageadjustmentrequired

micafungin

miconazole

midazolam

midodrine

milrinone

minocycline

mirabegron

mirtazapine

misoprostol

mitoxantrone

moclobemide

montelukast

morphine

moxifloxacin

mycophenolate

nabilone

nabumetone

Nephrotoxic.Activemetaboliteassume75%renalelimination
fordosageadjustment

nadolol

nadroparin

nafarelin

naloxone

naltrexone

Activemetabolitebutnodosageadjustmentrequired

naproxen

Nephrotoxic

naratriptan

natalizumab

nateglinide

nebivolol

Activemetabolitesassume75%renaleliminationfordosage
adjustment

nelfinavir

Activemetabolitebutnodosageadjustmentrequired

nevirapine

niacin

nicotine

nifedipine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Manufacturerrecommendsamaximumdailydoseof25mgin
patientswithsevererenalimpairment

Activemetaboliteassume75%renaleliminationfordosage
adjustment

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nimodipine

nitazoxanide

Activemetabolite

nitrofurantoin

Avoidinrenalimpairment

nitroglycerin

nitroprusside

nizatidine

norethindrone

norfloxacin

nortriptyline

Activemetabolitebutnodosageadjustmentrequired

octreotide

Reducedoseinsevererenalimpairment

ofloxacin

olanzapine

olmesartan

olsalazine

omalizumab

omega3fattyacids

omeprazole

ondansetron

orlistat

orphenadrine

Activemetabolitesassume75%renaleliminationfordosage
adjustment

oseltamivir

Activemetabolite.Dosageadjustmentrecommendedinsevere
renalimpairment

oxaprozin

Nephrotoxic

oxazepam

oxcarbazepine

oxtriphylline

oxybutynin

oxycodone

oxymetazoline

Routeofeliminationunknown

palifermin

paliperidone

Manufacturerrecommendsdosageadjustmentinrenal
impairment

palonosetron

Activemetabolitebutnodosageadjustmentrequired

pamidronate

Nephrotoxic

pantoprazole

paroxetine

pegfilgrastim

Polyethyleneglycolcomponentrenallyeliminated

peginterferonalfa

Polyethyleneglycolcomponentrenallyeliminated

penicillamine

Avoidnephrotoxic

penicillinG/V

pentamidine

pentazocine

pentoxifylline

perampanel

Notrecommendedinsevererenalimpairment

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Activemetabolitebutnodosageadjustmentrequired

Nephrotoxicwhengiveniv

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perindopril

Activemetaboliteassume75%renaleliminationfordosage
adjustment

perphenazine

phenazopyridine

phenelzine

pheniramine

phenobarbital

Activemetabolitebutnodosageadjustmentrequired

phenylephrine

phenytoin

pimozide

pinaveriumbromide

pindolol

pioglitazone

piperacillin

piperacillin/tazobactam

pipotiazine

Avoidinrenalimpairmentduetoriskofhypotension

piroxicam

Nephrotoxic

pizotifen

posaconazole

potassiumsalts

pramipexole

prasugrel

pravastatin

prazosin

prednisone

pregabalin

primaquine

primidone

Activemetabolitebutnodosageadjustmentrequired

procainamide

Activemetaboliteassume75%renaleliminationfordosage
adjustment

prochlorperazine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

procyclidine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

progesterone

proguanil

promethazine

propafenone

propranolol

propylthiouracil

prucalopride

pseudoephedrine

pyrazinamide

Avoidinsevererenalimpairment

pyridoxine

%renaleliminationincreasedwithlargedoses

pyrimethamine

Mayaccumulateinrenalimpairment

Activemetabolitebutnodosageadjustmentrequired

Activemetabolitebutnodosageadjustmentrequired

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quetiapine

quinapril

Activemetaboliteassume75%renaleliminationfordosage
adjustment

quinidine

Activemetabolitebutnodosageadjustmentrequired

quinine

quinupristin/dalfopristin

rabeprazole

raloxifene

raltegravir

ramipril

Activemetaboliteassume75%renaleliminationfordosage
adjustment

ranitidine

rasagiline

Conclusivedatanotavailableforrenallyimpairedpatients

rasburicase

repaglinide

ribavirin

Avoidinrenalimpairment

rifabutin

Activemetabolitebutnodosageadjustmentrequired

rifampin

Activemetabolitebutnodosageadjustmentrequired

rilpivirine

risedronate

Avoidinsevererenalimpairment

risperidone

Activemetaboliteassume75%renaleliminationfordosage
adjustment

ritonavir

Activemetabolitebutnodosageadjustmentrequired

rituximab

Nephrotoxic

rivaroxaban

Avoidinsevererenalimpairment

rivastigmine

rizatriptan

roflumilast

ropinirole

rosiglitazone

rosuvastatin

rotigotine

rufinamide

saquinavir

saxagliptin

Activemetaboliteassume75%renaleliminationfordosage
adjustment

scopolamine

secukinumab

selegiline

Activemetabolitebutnodosageadjustmentrequired

senna

%renallyeliminatedunknown

sertraline

sildenafil

silodosin

simeprevir

simvastatin

sitagliptin

Activemetabolitebutnodosageadjustmentrequired

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sodiumaurothiomalate

Avoidnephrotoxic

sodiumphosphates

%eliminatednotestablishedmayaccumulateinrenal
impairment

sofosbuvir

Nodoseadjustmentrecommendedinmildandmoderaterenal
impairment

solifenacin

Activemetabolite

sotalol

spectinomycin

Dosageadjustmentunnecessary

spironolactone

Avoid.Activemetaboliteassume75%renaleliminationfor
dosageadjustment

stavudine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

stiripentol

streptomycin

Nephrotoxicmonitorserumdrugconcentrations

sucralfate

Al++mayaccumulate

sulfadiazine

Nephrotoxic

sulfamethoxazole/

sulfasalazine

Activemetabolitebutnodosageadjustmentrequired

sulfinpyrazone

Avoidnephrotoxic

sulindac

Nephrotoxic.Activemetabolitebutnodosageadjustment
required

sumatriptan

tacrolimus

tadalafil

tamsulosin

telaprevir

telbivudine

telmisartan

temazepam

tenecteplase

tenofovir

Nephrotoxic

tenoxicam

Nephrotoxic

terazosin

terbinafine

teriflunomide

teriparatide

DonotuseifClCr<0.5mL/s

tetracycline

Nephrotoxic

theophylline

thiamine

thiothixene

tiaprofenicacid

ticagrelor

ticarcillin

ticarcillin/clavulanate

trimethoprim

Activemetaboliteassume75%renaleliminationfordosage
adjustment

Nephrotoxic

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ticlopidine

tigecycline

timolol

tinzaparin

tipranavir

tirofiban

tizanidine

tobramycin

tocilizumab

tolbutamide

tolcapone

tolterodine

topiramate

tramadol

Activemetaboliteassume75%renaleliminationfordosage
adjustment

trandolapril

Activemetaboliteassume75%renaleliminationfordosage
adjustment

tranexamicacid

tranylcypromine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

trazodone

triamterene

Avoid.Nephrotoxic.Activemetabolitebutnodosageadjustment
required

triazolam

trifluoperazine

trihexyphenidyl

trimeprazine

trimethoprim

trimipramine

triprolidine

triptorelin

Conclusivedatanotavailableforrenallyimpairedpatientsbut
dosageadjustmentmayberequired

trospium

Conclusivedatanotavailableforrenallyimpairedpatientsbut
dosageadjustmentmayberequired

Ltryptophan

ulipristal

ursodiol

ustekinumab

valacyclovir

Activemetaboliteassume75%renaleliminationfordosage
adjustment

valganciclovir

Nephrotoxic.Activemetaboliteassume75%renalelimination
fordosageadjustment

valproicacid

valsartan

vancomycin

vardenafil

varenicline

Nephrotoxicmonitorserumdrugconcentrations

Nephrotoxicmonitorserumdrugconcentrations

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vasopressin

vedolizumab

venlafaxine

Activemetaboliteassume75%renaleliminationfordosage
adjustment

verapamil

Activemetabolitebutnodosageadjustmentrequired

verteporfin

vigabatrin

vitaminB 12

vitaminC

vitaminD

vitaminE

voriconazole

vortioxetine

warfarin

xylometazoline

Routeofeliminationunknown

yohimbine

Avoid.Routeofeliminationunknown

zafirlukast

zanamivir

zidovudine

ziprasidone

zoledronicacid

zolmitriptan

Activemetabolitebutnodosageadjustmentrequired

zolpidem

zopiclone

zuclopenthixol

%renaleliminationincreasedwithlargedoses

Avoidivformulationinrenalimpairmentnephrotoxicvehicle

Reducedoseinsevererenalimpairment

aOmissionofadrugfromthistabledoesnotimplythatdosageadjustmentisNOTrequiredinrenalimpairment.Refertospecific
referencesfordosingindialysis.
bDosageadjustmentusuallynotrequiredunlessthereareactiveortoxicmetabolites(seeCommentscolumn).
cSeeTable1forsuggesteddoseadjustment.

Abbreviations:ASA=acetylsalicylicacidClCr=creatinineclearanceCYP3A4=cytochromeP4503A4

SuggestedReadings
DerschD,McCormackJ.Estimatingrenalfunctionfordrugdosing:rewritingthegospel?CanJHospPharm
200861(2):13843.Availablefrom:www.cjhponline.ca/index.php/cjhp/article/view/31.
VidalL,ShavitM,FraserAetal.Systematiccomparisonoffoursourcesofdruginformationregardingadjustmentofdose
forrenalfunction.BMJ2005331(7511):263.

References
1. McCormackJPCooperJ,CarletonB.Simpleapproachtodosageadjustmentinpatientswithrenalimpairment.AmJ
HealthSystPharm199754(21):25059.

TherapeuticChoices.CanadianPharmacistsAssociation,2015.Allrightsreserved.

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