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DrugInfluencesonNutrientLevelsandDepletion

DrugInfluencesonNutrientLevelsandDepletion

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DrugInfluencesonNutrientLevelsandDepletion

Somemedicationscanaffectthelevelsofcertainnutrientsinthebody.Thereisconsiderableinterestinusingnutritionalsupplementstocounteractthesepossibledruginduced"nutrientdepletions."Thechartbelow
showsthecurrentscientificunderstandingoftheserelationships,andsuggestedactions.
DRUGS
(IncludessomerepresentativeU.S.andCanadianBrandNames.)

NUTRIENT
DEPLETED

POSSIBLE
MECHANISM

COMMENTS&REFERENCES

Acetaminophen(Tylenol)

Glutathione

Acetaminophen
depletes
endogenous
glutathione.

It'snotknownifglutathionesupplements
wouldbebeneficial.5394

Aspirin,othersalicylates

FolicAcid

Decreasesprotein
bindingandserum
levels.

Folicacidappearstoberedistributed
ratherthanlostfromthebody.Redblood
cellfolatelevelsarenormal.
Supplementsarenot
needed.2677,9351,9360

Iron

Mucosaldamage
andGIbleeding,
evenif
asymptomatic,can
causechronic
bloodloss.

Monitorforsignsandsymptomsof
anemia.Encourageintakeofironrich
foodssincesupplementsmay
exacerbateGIirritation.8888,9515,95767

VitaminC

Increasesurinary
excretion.

DeficiencyofvitaminCisunlikely.Only
considersupplementationwithlongterm
therapyandsymptomsof
deficiency.105902,115267

Mucosaldamage
andGIbleeding,
evenif
asymptomatic,can
causechronic
bloodloss.

Monitorforsignsandsymptomsof
anemia.Encourageintakeofironrich
foodssincesupplementsmay
exacerbateGIirritation.8888,9515,95767

FolicAcid

Folatedependent
enzymesare
inhibitedbysome
NSAIDs.

Theclinicalsignificanceofthisisnot
known.

Biotin
Dibencozide
PantothenicAcid
(B5)

Destructionof
normalintestinal
microfloramaylead
todecreased

Theintestinalmicrofloraisreducedby
antibiotics.However,theBvitaminsare
mainlyobtainedfromthediet,andany
changesintheirproductionbyintestinal

ANALGESICS/ANTIINFLAMMATORIES

NonsteroidalAntiInflammatoryDrugs(NSAIDs):Diclofenac(Voltaren),Etodolac(Lodine),Fenoprofen(Nalfon),Flurbiprofen
Iron
(Ansaid),Ibuprofen(Advil,Motrin,etc),Indomethacin(Indocin),Ketoprofen(Orudis,Oruvail),Ketorolac(Toradol),Meclofenamate,
MefenamicAcid(Ponstel),Meloxicam(Mobic),Nabumetone(Relafen),Naproxen(Anaprox,Naprosyn,Naprelan),Oxaprozin
(Daypro),Piroxicam(Feldene),Sulindac(Clinoril),Tolmetin(Tolectin)

ANTIINFECTIVES
ANTIBIOTICS
AntibioticsGeneral:
Cephalosporins,Fluoroquinolones,Isoniazid,Macrolides,Penicillins,Sulfonamides,Tetracyclines,
Trimethoprim/Sulfamethoxazole

Pyridoxine(B6)
Riboflavin(B2)
Thiamine(B1)
VitaminB12
VitaminK

productionof
variousBvitamins
andvitaminK.
Some
cephalosporins
interferedirectly
withvitaminK
dependentclotting
factorproduction.

bacteriaisunlikelytobeclinically
significant.443443,6243,9502,9530
ReductioninvitaminKdependent
clottingfactorproductionmaybe
significantinpeoplewithotherrisk
factorsforlowvitaminKlevels.Monitor
thesepatients
closely.4437,4439,7135,9502,115136

FolicAcid

Disruptionof
normalintestinal
microflora
decreases
enterohepatic
circulationand
reabsorptionoffolic
acid,andmay
reducesynthesis.
Trimethoprim
inhibitsconversion
offolicacidtoits
activeform.

Folicacidsynthesizedbyintestinal
microfloraprobablydoesn'tcontribute
significantlytooverallfolatestatus,and
supplementsaren'tnecessarywith
normalcoursesofantibiotics.2677,4436
7,6243
Prolongedcoursesofhighdose
trimethoprimrarelycausemegaloblastic
anemia,andfolicacidsupplementshave
beenusedtopreventthis.However,
someevidencesuggestsfolicacid
supplementscanreducetheefficacyof
trimethoprim.Avoidsupplementsunless
recommendedbya
physician.2677,4468,4531,93827,93989

Aminoglycosides:Amikacin(Amikin),Gentamicin(Garamycin),Kanamycin(Kantrex),Netilmicin(Netromycin),Streptomycin,
Tobramycin(Nebcin)

Magnesium
Potassium

Increasedurinary
excretion,
associatedwith
druginducedrenal
damage.

Monitorpatientsforelectrolyte
disturbancesanddecliningrenal
funciton.Giveintravenouselectrolyte
replacementifnecessary,andconsider
dosereduction/discontinuationofthe
aminoglycoside.9519

CefditorenPivoxil(Spectracef)

AcetylLCarnitine
LCarnitine
PropionylL
Carnitine

Chronicuseof
cefditorencan
inducecarnitine
deficiency.

Longtermuseofcefditorenmight
requiresupplementation,butshortterm
usedoesnotseemtohaveaclinically
significanteffectoncarnitinelevels.12759

Chloramphenicol(Chloromycetin)

Niacinand
Niacinamide

Chloramphenicol
Deficiencyisunlikelyunlesstherapyis
mayinterferewith
prolonged.14514,145303
theactionsof
nicotinamide
adenine
dinucleotide(NAD).

Fluoroquinolones:Ciprofloxacin(Cipro),Enoxacin(Penetrex),Gatifloxacin(Tequin),Levofloxacin(Levaquin),Lomefloxacin
(Maxaquin),Moxifloxacin(Avelox),Norfloxacin(Noroxin),Ofloxacin(Floxin),Sparfloxacin(Zagam),Trovafloxacin(Trovan)

Calcium
Iron
Magnesium
Zinc

Formationof
insoluble
complexes
(prevents
absorptionofboth
nutrientand
fluoroquinolone).

Asignificanteffectonlevelsofthese
nutrientsisunlikelywhen
fluoroquinolonesaretakenatleast2
hoursbefore,or46hoursaftercalcium,
iron,magnesium,or
zinc.828,2682,3046,4412,4531

Neomycin(Mycifradin)

BetaCarotene
Dibencozide
VitaminA
VitaminB12

Reduced
absorption.

Notclinicallysignificantwithshortterm
useofneomycin.3046,5916,8434,105656

Pivampicillin(Pondocillin)

AcetylLCarnitine
LCarnitine

Chronicuseof
pivampicillincan

Longtermuseofpivampicillinmight
requiresupplementation,butshortterm

PropionylL
Carnitine

inducecarnitine
deficiency.

usedoesnotseemtohaveaclinically
significanteffectoncarnitinelevels.12759

Penicillins(sodiumcontaining):Carbenicillin(Geocillin),Mezlocillin(Mezlin),PenicillinGsodium(Pfizerpen),Piperacillin
(Pipracil),Ticarcillin(Ticar)

Potassium

Alargesodium
Monitorpotassiumlevels,andgive
loadispresentedto supplementsorswitchtoadifferent
thekidneys,
antibioticifnecessary.9519
resultinginsodium
reabsorptionand
potassium
excretion.

Sulfadiazine

AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Notknown.

Asinglecasereportdescribes
symptomaticLcarnitinedeficiencyina
patienttreatedwithpyrimethamineplus
sulfadiazinewhichreversedwhenboth
drugswerestopped.14600

Tetracyclines:Tetracycline(AchromycinV,Panmycin,Robitet,Robicaps,Sumycin,Teline,Tetracap,Tetracyn,Tetralan),
Demeclocycline(Declomycin),Doxycycline(BioTab,Doryx,DoxyCaps,Doxychel,DoxychelHyclate,Monodox,Periostat,Vibra
Tabs,Vibramycin),Minocycline(Dynacin,Vectrin),Oxytetracycline(Terramycin,UriTet)

Calcium
Iron
Magnesium
Zinc

Formationof
insoluble
complexes
preventsabsorption
ofbothnutrientand
tetracycline.
Doxycyclinedoes
notreducezinc
absorption.

Asignificanteffectonlevelsofthese
nutrientsisunlikelywhentetracyclines
aretakenatleast2hoursbefore,or46
hoursafterfoodorsupplements
containingcalcium,iron,magnesium,or
zinc.4412,4531,454950,4945

Potassium

Increasedrenal
excretion
associatedwith
nephropathy.

Duetoatoxicdegradationproductin
outdatedtetracyclines.Avoidoutdated
drugs.4425

AmphotericinB(Abelcet,AmBisome,Amphocin,Amphotec,Fungizone)

Magnesium
Potassium

Increasedurinary
excretion,
associatedwith
druginducedrenal
damage.

Monitorpatientsforelectrolyte
disturbancesanddecliningrenal
function.Giveintravenouselectrolyte
replacementifnecessary,andconsider
changingtoadifferentantifungal.9519

Fluconazole(Diflucan)

Potassium

Increasedurinary
excretion,
associatedwith
druginducedrenal
damage.

Monitorpotassiumlevelsandrenal
functioninpeopleonprolonged
fluconazoletherapy,andinthosewith
otherriskfactorsforhypokalemia.
Considerasupplementand
discontinuationoffluconazoleif
necessary.9519

FolicAcid

Folateantagonism.
Pyrimethamine
bindsto
dihydrofolate
reductase,
preventing
conversionoffolic
acidtoitsactive
form.

Atlowerpyrimethaminedoses,theneed
forsupplementationhasnotbeen
adequatelystudied.Advisepatientsto
maintaingooddietaryfolateintake.

ANTIFUNGALS

ANTIMALARIALS
Pyrimethamine(Daraprim)

Peoplereceivinglargerpyrimethamine
doses(thoserequiredtotreat
toxoplasmosis),shouldreceivefolinic
acid(leucovorin)toprevent
megaloblasticanemia.

Avoidfolicacid,whichantagonizesthe
therapeuticeffectsof
pyrimethamine.4425,4532,9380
AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Notknown.

Riboflavin(B2)

Caninterferewith
Maycauseriboflavindeficiency.Clinical
conversiontothe
significanceisnotknown.505,105212
activeformflavin
adenine
dinubleotide(FAD).

FolicAcid

Weakfolate
antagonist,
preventing
conversionoffolic
acidtoitsactive
form.

Rarecasesofmegaloblasticanemia,but
onlywithprolongedparenteraltherapy.
Folicacidsupplementsareusuallynot
necessary.9378

Magnesium

Increasedurinary
excretion,
associatedwith
druginducedrenal
damage.

Monitorserummagnesiumlevelsand
renalfunction.Giveoralorintravenous
supplementsasneeded.8872,96189

Adefovir

AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Increasedurinary
excretionofL
carnitine.

Adefoviratdosesof125500mg/dayis
associatedwithsignificantdoseand
durationrelateddecreasesinblood
carnitine.After12weeksoftherapywith
125250mg/day,decreasesof42%to
62%wereseen15502 while500mg/day
wasassociatedwitha66%decreasein
Lcarnitineafter2weeks.15503 Some
studiesusedasupplementofLcarnitine
500mg/dayduringadefovir
therapy.15501,15504 Adefovirisnowused
atalowerdoseof10mg/dayfor
treatmentofhepatitisB.Thereareno
reportsofsignificantreductionsin
carnitinebloodlevelsatthisdose,and
supplementsarenotnecessary.

Zidovudine(AZT,Combivir,Retrovir)

Copper
Dibencozide
VitaminB12
Zinc

SomeHIVpatients
takingzidovudine
havesubnormal
copperandvitamin
B12levels.The
mechanismis
unknown.

Preliminarydatasuggestlowercopper
levelsarenotharmfulandsupplements
shouldnotbeused.4986,8970
PreliminarydatasuggestvitaminB12
supplementsaren'thelpful.105313
ZincsupplementsmayreduceAIDS
relatedopportunisticinfections,buthave
alsobeenlinkedtoincreased
mortality.65656

Quinacrine

Asinglecasereportdescribes
symptomaticLcarnitinedeficiencyina
patienttreatedwithpyrimethamineplus
sulfadiazinewhichreversedwhenboth
drugswerestopped.14600

ANTIPROTAZOALS
Pentamidine(NebuPent,Pentacarinat,Pentam300)

ANTIRETROVIRALS

AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Zidovudine
interfereswith
mitochondrial
transportofL
carnitineinto
musclecells.

LowLcarnitinebloodlevelsarefoundin
somepeoplewithHIVinfection.
Zidovudineseemstoexacerbatethis,
andcanalsolowermusclecarnitine
levels,whichislinkedtosymptomsof
myopathy.3617,3618,11551 Lcarnitine
supplementsmightimprovefunctioning
ofmusclecellsaffectedby
zidovudine,3617,9885 buttherearenot
enoughdatatorecommendroutineuse
ofLcarnitinesupplementsforpatients
takingzidovudine.

FolicAcid

Inhibitsabsorption
inthe
gastrointestinal
tract.

Mayworsenthefolicaciddeficiency
associatedwithtuberculosis.
Recommendsupplementsifdietis
folatedeficient.4459,8441,9363,9388,9395

ANTITUBERCULOSISAGENTS
AminosalicylicAcid(ParaaminosalicylicAcid,Paser)

Cycloserine(Seromycin)

Ethambutol(Myambutol)

Iron

Reduced
gastrointestinal
absorption.

Monitorforsignsandsymptomsofiron
deficiencyandgivesupplementsif
needed.9574

Dibencozide
VitaminB12

Reduced
gastrointestinal
absorption.

MonitorvitaminB12levelsiftreatment
lastsmorethanone
month.4558,9395,9397,9574

FolicAcid

Possiblyreduces
absorptionor
increases
metabolism.

Rarecasesofmegaloblasticanemia
reported,butusuallywithotherfactors
contributingtofolatedeficiency.
Recommendsupplementsonlyifdietary
intakeisdeficient.4531,4536,9363

Niacinand
Niacinamide

Interferencewith
conversionof
tryptophanto
niacin.

Encephalopathyresponsiveto
niacinamidereportedrarely,usually
whencycloserineisusedwithother
drugswhichinterferewith
niacin.4531,145178

Pyridoxine(B6)

Inactivates
pyridoxal5'
phosphate,
increasing
pyridoxine
requirements.

Deficiencycancontributetothe
neurotoxicityandseizuresassociated
withcycloserine.Itisrecommendedthat
pyridoxine150300mg/daybetaken
withcycloserine.2677,3022,4459,

Ethambutolandits
metabolitechelate
copperandzincin
thegastrointestinal
tractanddecrease
theirabsorption.

Itisnotknownifcoppersupplementation
isbeneficial.4535,8971

Copper
Zinc

8894,9501

Zincdeficiencymaycontributetovisual
dysfunctionassociatedwithhigherdoses
ofethambutol.Monitorvisualfunction.
Itisnotclearifzincsupplementsare
helpful,andthereisconcerntheymay
interferewiththetherapeuticeffectsof
ethambutol.4453,11613,1163941

Ethionamide(TrecatorSC)

Niacinand
Niacinamide

Ethionamidehas
structural
similaritiesto
niacinamideand
mayinterferewith
itsactivity.

Encephalopathyresponsiveto
niacinamidereportedrarely,usually
whenethionamideisusedwithother
drugswhichmayinterferewith
niacin.145178

Isoniazid(INH,Laniazid)

Pyridoxine(B6)

Interfereswith
pyridoxine
metabolism.

Patientsreceiving>10mg/kg/dayofINH
shouldbesupplementedwith50100mg
ofpyridoxineperday.44812

Niacinand
Niacinamide

Isoniazidinhibits
theconversionof
tryptophanto
niacin.Italsohas
structural
similaritiesto
niacinamideand
mayinterferewith
itsactivity.

Mightinducepellagraiftakenforlong
periods,particularlyinpoorlynourished
patientsandthosetakingotherdrugs
whichinterferewithniacin.2677,4865
6,6243,14514,14520

Pyrazinamide

Niacinand
Niacinamide

Pyrazinamidehas
structural
similaritiesto
niacinamideand
mayinterferewith
itsactivity.

Deficiencyoccursrarely,butrespondsto
niacinamidesupplements.14529

Rifampin(Rifadin,Rimactane,Rofact)

VitaminD

Increasedhepatic
metabolismof
vitaminDdueto
enzymeinduction.

Thismaycauseosteomalaciaiftherapy
lastsmorethan1yearandvitaminD
intakeislow.Monitorcalciumand
vitaminDlevelsandconsider
supplementsifnecessary.Isoniazid
takenconcurrentlymaycauseliver
enzymeinhibitionandpreventthis
effect.115615

VitaminK

Possiblydecreased Considersupplementsinpeoplewith
gastrointestinal
otherriskfactorsforvitaminK
absorption,
deficiency.115178
destructionof
vitaminK
producingbacteria,
andinterference
withregenerationof
vitaminKfrom
inactivemetabolite.

Magnesium

Chelationand
increased
excretion.

Monitormagnesiumlevelsandgive
supplementsasnecessary.8869,9617

Aldesleukin(Interleukin2,IL2,Proleukin)

Magnesium

Intracellularshiftof
magnesium.

Supplementsusuallynotneeded.Serum
magnesiumlevelsnormalizeafterthe
courseiscompleted.8874

Amifostine(Ethyol)

Magnesium

Increasedurinary

Thisisusuallyonlyatransienteffect,with

ANTIVIRALS
Foscarnet(Foscavir)

ANTICANCERDRUGS

excretion.

levelsreturningtobaselinein24
hours.9625

Busulfan

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknownbut
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Cisplatin(PlatinolAQ),Carboplatin(Paraplatin)

AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Increasedurinary
excretionofL
carnitine.

CisplatinmightincreaseLcarnitine
mobilizationduetotissueinjury,and
reducedrenaltubularreabsorptiondue
torenalinjury.Lcarnitinedeficiencyis
unlikelyinpeoplewhocanmaintain
adequatedietaryintake.3642

Magnesium

Increasedurinary
excretionprobably
associatedwith
druginducedrenal
damage.

Hypomagnesemiaworsenswith
repeatedcoursesoftreatment,andis
moreseverewithcisplatinthan
carboplatin.Monitormagnesiumlevels
andgivesupplementsas
necessary.9626

Potassium

Renaltubular
damagecausedby
cisplatinincreases
lossofelectrolytes
including
potassium.

Hypokalemiaisasymptomaticinmany
patients,butcanbeassociatedwith
acuteparalysisorchronicmuscle
weakness.(15509,15510,15511)Monitor
electrolytescloselyinpatientsreceiving
cisplatinandusesupplementswhen
necessary.

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknownbut
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Zinc

Increasedurinary
excretion.

Levelsusuallyreturntonormalwithin24
48hoursafteradose.116223

Cyclophosphamide(Cytoxan,Neosar)

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknownbut
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

CytosineArabinoside(CytosarU)

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknown
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Dexrazoxane(Zinecard)

Zinc

Chelationofmetal Dexrazoxaneincreasesurinaryzinc
ionsincludingzinc, excretion10fold.11632Theclinical
leadingto
significanceofthisisnotknown.
increasedurinary

excretion.
Doxorubicin(Adriamycin,Rubex,Doxil)

Riboflavin(B2)

Formationof
Thismightcontributetodoxorubicin
inactivecomplexes, toxicity,butitisnotknownifriboflavin
interferencewith
supplementsarehelpful.9533,1052830
bindingand
conversiontoactive
form,increased
renalexcretion.

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknownbut
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Etoposide(Etopophos,VePesid,Toposar)

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknownbut
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Ifosamide(Ifex)

AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Increasedurinary
excretionofL
carnitine.

ThismightbeduetobindingofL
carnitinewithametaboliteof
ifosfamide.3641,11558 Theclinical
significanceofthisfindingandtheroleof
Lcarnitinesupplementsinpeople
treatedwithifosfamideareunknown.

Fluorouracil(5FU,Adrucil)

Niacinand
Niacinamide

Interferencewith
conversionof
tryptophanto
niacin.

Cancausepellagrararely,inpeoplewith
poornutritionalintakeormalabsorption.
Rapidlyreversedbyniacin
supplements.14514,14519

Thiamine(B1)

Mightinterferewith
theactivationof
thiamine,or
increaseits
breakdown.

Thereisn'tsufficientdatatorecommend
routineuseofsupplements.10552

VitaminE

Highdosesof
chemotherapymay
reducelevelsof
vitaminE.

Theclinicalsignificanceisunknownbut
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Mercaptopurine(6MP,Purinethol)

Niacinand
Niacinamide

Interfereswith
conversionof
niacinto
nicotinamide
adenine
dinucleotide(NAD),
duetostructural
similaritiesto
adenine.

Maycausepellagraifhighdosesare
usedforprolongedperiods(e.g.,250
mg/dayfor4years).Consider
supplementsasnecessary.145145

Methotrexate(Rheumatrex)

VitaminE

Highdosesof

Theclinicalsignificanceisunknown,but

chemotherapy
seemstoreduce
levelsofvitaminE.

thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

FolicAcid

Folateantagonist,
preventing
conversionoffolic
acidtoitsactive
form.

Folicacidsupplementscaninterferewith
theactionsofmethotrexate.Avoid,
unlessrecommendedbyan
oncologist.9420

VitaminE

Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.

Theclinicalsignificanceisunknown,but
thereissomeconcernthatlowlevels
mayincreaseriskoftoxicity.Levelsmay
returntonormalbetweencourses.Itis
notknownifsupplementsare
helpful.98,10366,115889

Insulin

Magnesium

Mayincreaseloss
ofmagnesiumin
theurine.

Decreasedabsorptionandosmotic
diuresismayalsocontributetolow
magnesiumlevelsindiabeticpatients.
Theclinicalsignificanceofthiseffectof
insulinisunclear.Monitormagnesium
levels.13381

Metformin(Glucophage)

FolicAcid
Dibencozide
VitaminB12

Malabsorptionof
dietaryvitaminB12
andpossiblyfolic
acid.

TheGlucophagepackageinsert
recommendsobtaininghematological
parametersannuallyandobtainingB12
levelsat23yearintervalsinpatientsat
increasedriskforB12
deficiency.Symptomaticfolicacid
deficiencyisunlikely.Givesupplements
onlyifclinicaljudgmentwarrants
it.32,44901,7839,7841,8834,95203

Thiamine(B1)

Theoretically,
metforminmight
reducethiamine
activity.

Thismightresultinmorepyruvate
enteringtheKreb'scycleandbeing
convertedtolacticacid.Thiscould
contributetometformininducedlactic
acidosis,buttheprocesshasnotbeen
substantiatedinhumans.9536,11466

Azathioprine(Imuran)

Niacinand
Niacinamide

Azathioprineis
metabolizedto6
mercaptopurine
whichmayinhibit
conversionof
niacintoitsactive
form,nicotinamide
adenine
dinucleotide.

Pellagrahasoccurredinpeoplewith
marginalniacinstatuswhotake
azathioprine.Mostpeopleprobablydo
notneedsupplements.14513

Colchicine

BetaCarotene

Disruptionof
intestinalmucosal
functionby

Colchicine12mg/daydoesn'taffect
betacaroteneserumlevels,buthigher
dosesmay.Givesupplementsonlyif

Thiotepa(Thioplex)

ANTIDIABETESAGENTS

ANTIGOUT/ANTIRHEUMATIC

colchicinecan
reduceabsorption.

clinicaljudgementwarrantsit.4543,5921

Dibencozide
VitaminB12

Disruptionof
intestinalmucosal
functionby
colchicinecan
reduceabsorption.

Colchicine12mg/daydoesn'taffect
vitaminB12serumlevels,buthigher
dosesmay.MonitorvitaminB12levelsin
peopletakinglargedosesforprolonged
periods,andconsidersupplementsif
necessary.45435,5921

Methotrexate(Rheumatrex)

FolicAcid

Folateantagonism.
Bindsto
dihydrofolate
reductase,
preventing
conversionoffolic
acidtoitsactive
form.

Inpeopletakinglongterm,lowdose
methotrexateforrheumatoidarthritisor
psoriasis,reducedfolatelevelsincrease
theriskofsideeffects.Recommendfolic
acid1mg/day,especiallyinpeoplewith
alowdietaryfolateintakeorwhoare
experiencingsideeffects.Thisdoesn't
reducetheefficacyofmethotrexatein
theseconditions.768,2162,4492
4,4546,9369,941820
Peopletakingmethotrexateforcancer
shouldavoidfolicacidsupplements
unlessrecommendedbytheironcologist,
sincetheymayinterferewiththe
anticancereffects.9420

Penicillamine(Cuprimine,Depen)

Copper
Iron
Magnesium

ChelationintheGI
tract,decreasing
absorptionofthese
minerals.

Deficiencyisunlikelyunlessthereare
othercontributingfactors.Ifsupplements
areneeded,separatedosesfrom
penicillaminebyatleast2
hours.4453,4531,45345,9630

Pyridoxine(B6)

Inhibitionof
pyridoxineactivity,
possiblybyforming
aninactivecomplex
withpyridoxal5'
phosphate.

Thismaycontributetoperipheraland
opticneuropathy.Itisrecommendedthat
patientstreatedwithpenicillaminefor
Wilson'sdiseasetakepyridoxine25
mg/day.Inotherconditions,monitorfor
signsofneuropathy,suchasnumbness
andtingling.Supplementsof50150
mg/dayhavebeenusedwhen
necessary.3092,4534,8897

Zinc

Chelationofzinc
whichcanincrease
urinaryzinc
excretion,butcan
alsoincreaseGI
absorptionofzinc.

Theseeffectsusuallycanceleachother
out.Therearerarecasesofsymptomatic
zincdeficiency.Usezincsupplements
onlyifclinically
needed.2678,4534,9630,116124

Pyridoxine(B6)

Formationofan
inactivecomplex
withpyridoxal5'
phosphate,and
increased
excretion.

Monitorforearlysignsofneuropathy
suchasnumbnessandtingling.Give
supplementsifnecessary.2677,3022,4533

CARDIOVASCULAR
ANTIHYPERTENSIVES
Hydralazine(Apresoline)

Captopril(Capoten)

Zinc

Bindingofzinc,
leadingto
increasedurinary
elimination.

Zincdepletionmaycontributetotaste
lossassociatedwithcaptopril.Probably
onlyoccurswithhighdoses(>150
mg/day)takenforprolongedperiods.
Routinesupplementsarenot
necessary.25,26,6543,1161821

Magnesium

Reduced
reabsorptionof
magnesiuminthe
renaltube,leading
tomagnesium
excretion.

Lowmagnesiumlevelscanincreasethe
riskofarrhythmias.Hypomagnesemia
morelikelywithconcurrentdiureticuse.
Monitormagnesiumlevelsasclinical
judgmentwarrantsandgive
supplementsifnecessary.4556,9613,9631

HMGCoAReductaseInhibitors("Statins"):
Atorvastatin(Lipitor)
Fluvastatin(Lescol)
Lovastatin(Mevacor)
Pravastatin(Pravachol)
Rosuvastatin(Crestor)
Simvastatin(Zocor)

CoenzymeQ10

Blockingof
synthesisof
mevalonicacid,
whichisa
precursorof
coenzymeQ10.

SerumlevelsofcoenzymeQ10are
reducedbutmusclelevelsarenot
affected.Therefore,thisisprobablynot
clinicallysignificant.3367,3370,4404

BileAcidSequestrants:
Cholestyramine(LoCHOLEST,Prevalite,Questran)
Colestipol(Colestid)

BetaCarotene
VitaminA
VitaminE
VitaminK

Reduced
absorptionoffat
andfatsoluble
vitamins.Reduced
plasmalipidsmay
reducetheamount
ofbetacarotene
andvitaminsAand
Ecarriedinthe
blood.

Reductioninplasmabetacarotene,and
vitaminA,E,andKlevelsissometimes
reportedbutlevelsusuallyremainwithin
normallimits,evenafterseveralyearsof
treatment.Routinesupplementsarenot
necessary.Monitorpatientscloselyif
theyhaveotherriskfactorsfor
hypoprothrobinemiaorbleeding.4454

FolicAcid

Reduced
absorption.

Lowfolatelevelshavebeenreportedin
childrentakinglargedosesof
cholestyramineforseveralmonths,but
theclinicalsignificanceisnotclear.
Therearenoreportsofdeficiencyin
adults.Encouragepatientstomaintain
gooddietaryintakeoffolate.4455,4461

Iron

Reduced
absorption.

Clinicallysignificantirondeficiencyhas
notbeenreported.Ifpatientsneediron
supplementsforotherreasons,advise
themtoseparatedosesfrombileacid
sequestrantsbyatleast4hours.9566

Dibencozide
VitaminB12

Reduced
absorptiondueto
bindingofintrinsic
factorandvitamin
B12intrinsicfactor
complexes.

Absorptionisnotcompletelyblocked.
Deficiencyisunlikelyunlessthepatient
hasotherriskfactorsforvitaminB12
deficiency.4455,105423

Calcium
VitaminD

Reduced
absorptionof

Osteomalaciahasoccurredrarelyin
peopletakinghighdoses(e.g.,>32

CARDIACGLYCOSIDES
Digoxin(Lanoxicaps,Lanoxin)

CHOLESTEROLREDUCINGDRUGS

10,8915,1209

8,44601,5919,105667,11519

vitaminD,whichin g/daycholestyramine)forseveralyears,
turnreduces
andhavingotherriskfactorsforvitamin
calciumabsorption. Ddeficiency.Suchpatientsmayneed
vitaminDandcalciumsupplements,but
mostotherpatientsdo
not.2672,4458,44601,5655,5809,9627
Magnesium

Possiblyreduced
absorptionand
increasedurinary
magnesium
excretion.

Magnesiumdeficiencyhasnotbeen
reported.
Supplementsarenotlikelytobe
needed.4096,11548,11587

PhosphateSalts

Cholestyramine
canbindphosphate
inthegutand
reduceits
absorption.

Cholestyraminedosesof0.2to1.1
grams/kg/dayinchildrenand1216
grams/dayinadultshavebeen
associatedwithreducedphosphate
levels.4455,5838Mostpeopletaking
cholestyraminedon'tneedphosphate
supplementsunlesstheirdietaryintake
islow.Thisinteractioncanbeavoidedby
separatingphosphateand
cholestyramineadministrationbyatleast
2hours.

Colestipolcanbind
phosphateinthe
gutandreduceits
absorption.

Inmostpeopletakingcolestipol,serum
phosphatelevelsremainwithinnormal
limits.4460Mostpeopletakingcolestipol
don'tneedphosphatesupplements
unlesstheirdietaryintakeislow.This
interactioncanbeavoidedbyseparating
phosphateandcholestyramine
administrationbyatleast2hours.

Gemfibrozil(Lopid)

VitaminE

Mechanism
unknown.

Somestudieshavereportedreduced
serumvitaminElevelswithgemfibrozil,
buttheclinicalsignificanceis
unknown.4096,11548,11587

LoopDiuretics:
Bumetanide(Bumex,Burinex),
Ethacrynicacid(Edecrin),
Furosemide(Lasix),
Torsemide(Demadex)

Calcium
Magnesium
Potassium

Increasedurinary
excretion.

Electrolytedisturbancesmorelikelywith
higherdoses.Hypokalemiaand
hypomagnesemiaoccurmostcommonly.
Mayneedtousepotassiumand/or
magnesiumsupplements,oradda
potassiumsparingdiuretic(whichwill
alsosparemagnesium).4412,96134,9622

FolicAcid

Possiblyincreased
urinaryexcretion.

Dataisverylimited,andtheneedforfolic
acidsupplementationhasnotbeen
adequatelystudied.1898

Pyridoxine

Increasedurinary
excretion
pyridoxine.

Intravenousfurosemideinpeoplewith
chronicrenalfailureincreasesurinary
excretionof
pyridoxine.8896,9525 However,people
withhypertensiontreatedwithoral
diureticsforseveralyearsseemtohave
normalserumpyridoxine
levels.1898 Pyridoxinesupplements

aren'tusuallynecessary.
Thiamine(B1)

Increasedthiamine
excretiondueto
increasedurinary
flow.

Thiaminedeficiencymayoccurinelderly
peoplewithpoordietaryintakewhoare
onhighdosesofdiuretics(e.g.>80mg
furosemide/day)forseveralmonths.
Thiaminedeficiencymayworsenheart
failure.Asupplementof200mg/dayhas
improvedcardiacfunctioninsome,but
notallthiaminedeficientpeopleon
diuretics.Therearenotenoughdatato
recommendroutineuseof
supplements.12836,105069

VitaminC

Increasedurinary
lossesofvitaminC,
probablydueto
increasedwater
excretion.

Reportedinpeoplewithchronicrenal
failurewhoreceiveda20mg
intravenousdoseoffurosemide.
SignificantvitaminCdepletionhasn't
beenreportedwithchronicoraluseof
furosemideorotherdiuretics.9525

ThiazideandThiazideDerivatives:
Bendroflumethiazide(Naturetin),
Benzthiazide(Exna),
Chlorothiazide(Diuril),
Chlorthalidone(Hygroton,Thalitone),
Hydrochlorothiazide(Esidrix,Hydrodiuril,Oretic),
Hydroflumethiazide(Diucardin,Saluron),
Indapamide(Lozide,Lozol),
Methyclothiazide(Aquatensen,Enduron),
Metolazone(Mykrox,Zaroxolyn),
Polythiazide(Renese),
Quinethazone(Hydromox),
Trichlormethiazide(Diurese,Metahydrin,Naqua)

Magnesium
Potassium
Zinc

Increasedurinary
excretion.

Electrolytedisturbancesaremorelikely
withhigherdoses.Hypokalemiaand
hypomagnesemiaoccurmostcommonly.
Mayneedtousepotassiumand/or
magnesiumsupplements,oradda
potassiumsparingdiuretic(whichwill
alsosparemagnesium).4412,96134,9622

FolicAcid

Possiblyincreased
urinaryexcretion.

Dataareverylimited,andtheneedfor
folicacidsupplementationhasnotbeen
adequatelystudied.1898

Thiamine(B1)

Increasedthiamine
excretiondueto
increasedurinary
flow.

Thiaminedeficiencymayoccurinelderly
peoplewithpoordietaryintakewhoare
onhighdosesofdiureticsforseveral
months.Thiaminedeficiencymay
worsenheartfailure.Asupplementof
200mg/dayhasimprovedcardiac
functioninsomethiaminedeficient
peopleondiuretics.Therearenot
enoughdatatorecommendroutine
supplements.12836,105069

Triamterene(Dyrenium)

FolicAcid

Reduced
absorptionoffolic
acidandreduced
conversiontothe
activeform.

Megaloblasticanemiaisrareunless
patientsareonchronictherapyandhave
poordietaryintakeorotherriskfactors
forfolatedeficiency.Monitorfolatestatus
inthesesituationandconsider
supplementsifnecessary.4425,4536
7,9375

CENTRALNERVOUSSYSTEM
ANTICONVULSANTS
Carbamazepine(Atretol,Epitol,Tegretol)

Biotin

Competitive
inhibitionof
absorption,
increased

Theclinicalsignificanceofthisisnot
known.Itisnotknowniftakingbiotin
supplementsisnecessary.172,175
6,11698700,145012

breakdown,and
decreasedrenal
tubular
reabsorption.

Phenytoin(Dilantin),
Fosphenytoin(Cerebyx)

AcetylLCarnitine
LCarnitine
PropionylL
Carnitine

Possiblyincreased
metabolismor
decreased
synthesis.

Itisnotknownifcarnitine
supplementationisnecessary.1911,12758

FolicAcid

Decreased
intestinal
absorptionand
inductionofhepatic
microsomal
enzymesleadingto
increasedfolicacid
metabolism.

Megaloblasticanemiaduetofolicacid
deficiencyhasn'tbeenreportedwith
carbamazepine.Lowfolicacidlevels
mightcontributetomentalchangesin
somepeopleoncarbamazepine,but
folicacidsupplementsmayworsen
seizurecontrol.Advisepatientsto
consulttheirphysicianbeforestarting
folicacidsupplements.44269,9359

Calcium
VitaminD

Increasestherate
ofvitaminD
metabolismleading
todecreasedlevels
ofvariousformsof
vitaminD.
Decreasedvitamin
Dlevelsreduce
calciumabsorption.

Hypocalcemiaandosteomalaciahave
occurredwithlongtermanticonvulsant
therapy.Advisepatientstaking
carbamazepinefor6monthsorlongerto
havetheirvitaminDandcalciumlevels
checked.Supplementsmaybe
needed.2675,10578

VitaminK

Inductionofliver
enzymesmay
increasevitaminK
metabolism,
producinga
significant
decreaseinvitamin
Klevelsin
neonates,who
haven'tbuiltup
storesofthe
vitamin.

Increasesriskofneonatalintracranial
hemorrhage.Womenwhoneedtotake
carbamazepineduringpregnancy
shouldtakevitaminK,1020mg/day,
duringthelastmonthofpregnancy.The
babyshouldreceivevitaminK
immediatelyafterdelivery.10582,11521
5,115334

VitaminE

Childrentaking
Theclinicalsignificanceisunknown.Itis
carbamazepine
notknownifvitaminEsupplementsare
seemtohavelower beneficial.115748
vitaminElevels
comparedto
childrennot
receiving
carbamazepine.

Biotin

Competitive
inhibitionof
absorption,
increased
breakdown,and
decreasedrenal
tubular
reabsorption.

Theclinicalsignificanceofthisisnot
known.Itisnotknowniftakingbiotin
supplementsishelpful.1756,11698
700,14501

FolicAcid

Reduced
absorption,
increased
metabolism,and
increaseddemand
forfolateasa
coenzymefor
inducedhepatic
enzymes.

Folicacidsupplementsmayreduce
phenytoinsideeffects,butcanalso
reducephenytoinserumlevelsandmay
independentlyworsenseizurecontrol.
Advisepatientstoconsultaphysician
beforestartingfolicacid
supplements.4427,4471,4477,4536,93549

AcetylLCarnitine
Lcarnitine
PropionylL
Carnitine

Possiblyincreased
metabolismor
decreased
synthesis.

Itisnotknownifcarnitine
supplementationisnecessary.1911,12758

Niacin/Niacinamide Mechanism
unknown.

Casereportsdescribepellagralike
symptomswithphenytoin,butthisisrare
andsupplementsaregenerallynot
needed.145223

Thiamine(B1)

Mechanism
unknown.

Thiaminedeficiencymightcontributeto
neurologicsideeffects,butthereis
insufficientevidencetorecommend
supplements.105102

Dibencozide
VitaminB12

Reduces
absorptionof
vitaminB12.

Thismayexacerbatethemegaloblastic
anemiaassociatedwithphenytoin,which
isprimarilycausedbyfolatedeficiency.
Encouragepatientstomaintain
adequatedietaryvitaminB12intake.
MonitorvitaminB12andfolateif
symptomsofanemiadevelop.7843,10502
5

Calcium
VitaminD

Increasestherate
ofvitaminD
metabolismleading
todecreasedlevels
ofvariousformsof
vitaminD.
Phenytoinmayalso
increasetherenal
excretionofvitamin
Dmetabolites.
Decreasedvitamin
Dlevelsreduce
calciumabsorption.

Hypocalcemiaandosteomalaciahave
occurredwithlongtermanticonvulsant
therapy.Advisepatientstakingphenytoin
for6monthsorlongerthattheyshould
havetheirvitaminDandcalciumlevels
checked.Supplementsmaybe
needed.2675,44301,4475,10578

VitaminE

Childrentaking
phenytoinseemto
havelowervitamin
Elevelscompared
tochildrennot
receiving
phenytoin.

Theclinicalsignificanceisunknown.Itis
notknownifvitaminEsupplementatsare
beneficial.115748

VitaminK

Inductionofliver
enzymesmay
increasevitaminK
metabolism,

Increasedriskofneonatalintracranial
hemorrhage.Womenwhoneedtotake
phenytoinduringpregnancyshouldtake
vitaminK,1020mg/day,duringthelast

producinga
monthofpregnancy.Thebabyshould
significant
receivevitaminKimmediatelyafter
decreaseinvitamin delivery.10582,115215,115334
Klevelsin
neonateswho
haven'tbuiltup
storesofthe
vitamin.

Phenobarbital(Luminal,Solfoton)
Primidone(Mysoline)

Zinc

Maychelatezinc
andcouldreduce
absorption.

Occasionalreportsofreducedzinclevels
buttheclinicalsignificanceisunclear
andsupplementsareunlikelytobe
necessary.11577,1165960,11663,11669

Biotin

Competitive
inhibitionof
absorption,
increased
breakdown,and
decreasedrenal
tubular
reabsorption.

Theclinicalsignificanceofthisisnot
known.Itisnotknowniftakingbiotin
supplementsishelpful.172,1756,11698

FolicAcid

Reduced
absorption,
increased
metabolism,and
increaseddemand
forfolateasa
coenzymefor
inducedhepatic
enzymes.

Reducedfolicacidlevelsassociatedwith
phenobarbitalorprimidonetreatment
occasionallyleadtomegaloblastic
anemia,andmaycontributeto
neurologicalsideeffectsandmental
changes.However,folicacid
supplementscanworsenseizurecontrol.
Advisepatientstoconsultaphysician
beforestartingfolicacid
supplements.4427,4530,4536,9333,93549

Dibecozide
VitaminB12

Reduced
absorption

Encouragepatientstomaintain
adequatedietaryvitaminB12intake.
MonitorvitaminB12statusifsymptomsof
anemiadevelop.7843,105025

AcetylLCarnitine
LCarnitine
PropionylL
Carnitine

Possiblyincreased
metabolismor
decreased
synthesis.

Itisnotknownifcarnitine
supplementationisnecessary.1911,12758

VitaminE

Childrentaking
Theclinicalsignificanceisunknown.Itis
phenobarbital
notknownifvitaminEsupplementsare
seemtohavelower beneficial.115748
vitaminElevels
comparedto
childrennot
receiving
phenobarbital.

Calcium
VitaminD

Increasedrateof
vitaminD
metabolismleading
todecreasedlevels
ofvariousformsof
vitaminDand
reducedcalcium

700,145012

Hypocalcemiaandosteomalaciacan
occurwithlongtermanticonvulsant
therapy.Advisepatientstaking
phenobarbitalorprimidonefor6months
orlongerthattheyshouldhavetheir
vitaminDandcalciumlevelschecked.
Supplementsmaybeneeded.2675

absorption.
VitaminK

ValproicAcid(Depakene,Depakote)

FolicAcid

Inductionofliver
enzymesmay
increasevitaminK
metabolism,
producinga
significant
decreaseinvitamin
Klevelsin
neonates,who
haven'tbuiltup
storesofthe
vitamin.

Increasedriskofneonatalintracranial
hemorrhage.Womenwhoneedtotake
theseanticonvulsantsduringpregnancy
shouldtakevitaminK,1020mg/day,
duringthelastmonthofpregnancy.The
babyshouldreceivevitaminK
immediatelyafterdelivery.10582,11521

Mechanism
unknown.

Reducedlevelsoccuroccasionally,but
symptomaticfolicaciddeficiencyhasnot
beenreported.Avoidsupplementssince
theymayworsenseizurecontrol.4427

5,15334

8,93556,9359

AcetylLCarnitine
LCarnitine
PropionylL
Carnitine

Possiblyincreased
metabolismor
decreased
synthesis.

Valproicacidsupplementmaynotbe
necessaryinpatientswhohave
adequatenutritionintake.1911,4528

Niacinand
Niacinamide

Mechanism
unknown.

Therearerarecasereportsofdeficiency,
butmostpeopledonotneed
supplements.14505,14523

Zinc

Maybindwithzinc,
possiblyreducing
serumandtissue
levels.

Dataregardingtheeffectofvalproateon
zinclevelsareconflicting.Somesuggest
thatloweredzinclevelsmightcontribute
tosideeffectsofvalproate.Mostpeople
areunlikelytoneedzinc
supplements.1165262

Levodopa(LDOPA,Larodopa,Dopar)

Potassium

Increasedurinary
potassiumlosses
occurinsome
peopletreatedwith
levodopa.The
mechanismisn't
clear,buttheeffect
doesn'toccurwhen
aperipheral
decarboxylase
inhibitor,suchas
carbidopa,isused
withlevodopa(as
inSinemet).

Thisinteractionisunlikelytobe
significantsincemostpatientsget
levodopaincombinationwith
carbidopa.7201

Levodopa/Cabidopa(Sinemet)

Niacinand
Niacinamide

Carbidopamay
reduceconversion
oftryptophanto
niacin.

Clinicallysignificantniacindeficiency
hasnotbeenreportedandsupplements
areunlikelytobenecessary.14516

Chlorpromazine(Thorazine)

Riboflavin(B2)

Interferencewith

Theseeffectsoccurinanimals,butthere

9,5798,9612,12758

Dopamineagonists

conversiontoactive arenotenoughdatatoknowifthisis
form,andincreased clinicallysignificantin
renalexcretion.
humans.10515,1051821
Gastrointestinals
Antacids
AluminumSalts(Amphojel,Alternajel,Basaljel,etc),MagnesiumSalts(MagOx,MilkofMagnesia,etc),

Calcium
PhosphateSalts

Aluminumsalts
bindphosphatein
thegastrointestinal
tract.Thisreduces
phosphatelevels,
whichinduces
movementof
calciumfrombones
intotheblood,
increasingurinary
calciumexcretion.
Highserum
magnesiumlevels
canincrease
urinarycalcium
excretion.

Prolongedadministrationoflargedoses
ofantacidsmayleadtohypocalcemia
and/orhypophosphatemia.Avoid
prolongedadministrationoflargedoses,
exceptwhenusedasaphosphate
binderinpatientswithrenalfailure.2730
1,3371,4400,4623,5979

Chromium

Antacidsmay
Unlikelytobeclinicallysignificant.7135
reducechromium
absorptionfromthe
gastrointestinal
tract.

FolicAcid

Increasedintestinal
pHproducedby
antacidsmay
reducefolicacid
absorption.

Longtermuseoflargedosesofantacids
cancausefolatedepletionifdietary
intakeisverylow.Mostpeopledon't
needsupplements.2677,8441

Iron

Increasedgastric
pHreducesiron
solubilityand
absorption.

Unlikelytocauseirondeficiency.Ifiron
supplementsareneededforother
conditions,separatedosingtimesas
muchaspossible.Monitorforadequate
responsetoiron.3046,3072,4539

FolicAcid

Competitive
inhibitionoffolate
absorption,and
interferencewith
breakdownof
dietaryfolatetoits
absrobableform.
Hemolysiscaused
bysulfasalazine
canincreasefolate
requirementsfor
redbloodcell
formation.

Decreasedfolatelevelsareassociated
withprolongedsulfasalazinetherapy,
especiallyindosesabove2grams/day.
Thismayleadtomegaloblasticanemia,
hyperhomocysteinemia,andan
increasedriskofcoloncancerinpeople
withulcerativecolitis.Recommendthat
patientsincreasetheirdietaryfolate
intakeifpossible,ortakeasupplement,
especiallyiftheyhaveotherriskfactors
forfolatedeficiency.2677,4515

GIANTIINFLAMMATORIES
Sulfasalazine(Azulfidine,Salazopyrin)

HISTAMINE2BLOCKERS

7,4536,4560,9353,93767,9379

H2Blockers:
Cimetidine(Tagamet),
Famotidine(Pepcid),
Nizatidine(Axid),
Ranitidine(Zantac)

Calcium

Absorptionofsome Thereisnotanyevidenceofaclinically
calcium
significanteffectoncalcium
supplements,
levels.2738,43301,5060
especiallythe
carbonatesalt,is
decreasedby
increasedgastric
pH.

Chromium

IncreasedpHmay
causeformationof
lesssoluble
chromiumsalts,
reducing
absorption.

Theclinicalsignificanceofthisisnot
known.7135

FolicAcid

Reduced
absorptiondueto
increasedpH.

Asignificanteffectonfolicacidlevelsis
unlikelyunlessdietaryintakeisvery
low.4483,8441

Iron

Reducediron
absorptionfromthe
gastrointestinal
tractdueto
reductioninacid.

Reductioninabsorptionofdietary,non
hemeironoccurs,butanemiaisunlikely
withlongtermH2blockeruseinpeople
withnormalironstores.Supplements
maybeneededinpeoplewithother
factorscontributingtoiron
deficiency.4483,4539,45401,8876,9578

Dibencozide
VitaminB12

Decreasedgastric
acidreduces
cleavageofprotein
bounddietary
vitaminB12,
reducingthe
amountavailable
forabsorption.

Deficiencyisunlikelyunlessdietary
intakeofvitaminB12ispoor,orH2
blockersaretakencontinuouslyinhigh
dosesfor2yearsormore.Inthese
circumstances,monitorforvitaminB12
deficiencyandanemia.453941,9513

Zinc

Inhibitionofgastric
acidsecretion
mightreduce
absorptionofzinc.

Clinicallysignificantzincdepletionhasn't
beenreported.11636

BetaCarotene
Calcium
VitaminA
VitaminD
VitaminE
VitaminK

Decreases
gastrointestinal
absorption.

Occassionaluseofmineraloilisunlikely
tocausedeficiency.Advisepatientsto
avoidlargedosesorregularuseof
mineraloil.4454,44956

PhosphateSalts

Mineraloilreduces
absorptionof
vitaminD,which
actstoincrease
phosphate
absorptioninthe
gastrointestinal
tractand
reabsorptioninthe

Occasionalorshorttermuseofmineral
oilisn'tlikelytohaveaclinically
significanteffectonphosphate
levels.505,4495

4,9528

LAXATIVES
MineralOil

kidneytubules.
SodiumPhosphates
(FleetPhosphoSoda)

Magnesium
Potassium

Increasedlossof
electrolytesfrom
gastrointestinal
tract.

Highdoses(suchasthoseusedfor
preoperativebowelcleansing)can
causesevereelectrolytedisturbances.
Avoidhighdosesandmonitorelectrolyte
levelsintheelderlyandotherswithrisk
factorsforhypomagnesemiaor
hypokalemia.8877,9531,96156

StimulantLaxatives:Senna(Senexon,Senolax,Senokot,SennaGen,Senokotxtra,BlackDraught,Gentlax,Dr.Caldwell
Senna,Fletcher'sCastoria,Dosalax),
BisacodylTablets(Bisacodyl,Uniserts,BiscoLax,Correctol,Dulcagen,Dulcolax,Feenamint,FleetLaxative)

Potassium

Increases
gastrointestinal
losses.

Excessiveuseofstimulantlaxativesmay
resultinhypokalemia.Limittoshortterm
useofrecommendeddoses.
Hypokalemiahasbeenreportedin
patientsundergoingshorttermbowel
cleansingregimens.Usewithcautionin
patientswhohaveotherriskfactorsfor
hypokalemia.44112,4425

Calcium
VitaminD

Decreases
gastrointestinal
absorption.

Prolongeduseofhighdosesofstimulant
laxativescancausehypocalcemiaand
osteomalacia.Limittoshorttermuseof
recommeneddoses.11530

FolicAcid
Iron

Reduced
absorptiondueto
formationof
complexesinthe
gastrointestinal
tract.

Supplementsmaybeneededwith
prolongedpancreaticenzyme
therapy.9374,9575,9585

BetaCarotene

Increasedgastric
pHmaydecrease
absorptionofbeta
carotene.

Reportedwithasingledoseofabeta
carotenesupplement.Whetherthereisa
clinicallysignificanteffectonabsorption
ofdietarybetacarteneisunknown.31

Calcium

Absorptionofsome Thereisn'tanyevidenceofaclinically
calcium
significanteffectoncalcium
supplements,
levels.2738,43301,5060
especiallythe
carbonatesalt,is
decreasedby
increasedgastric
pH.

Chromium

IncreasedpHmay
causeformationof
lesssoluble
chromiumsalts,
reducing
absorption.

FolicAcid

IncreasedpHcould UseofPPIsforseveralyearsdoesnot
reducefolate
seemtocausefolatedeficiency.
absorption.
Supplementsareprobablynot
necessary.4483,8441

PANCREATICENZYMES
Pancreatin(Donnazyme,Pancrezyme)
Pancrelipase(Cotazym,Creon,Pancrease,Ultrase,Viokase)

PROTONPUMPINHIBITORS
ProtonPumpInhibitors:Lansoprazole(Prevacid),Omeprazole(Losec,Prilosec),Rabeprazole(Aciphex),Pantoprazole
(Pantoloc,Protonix)

Theclinicalsignificanceofthisisnot
known.7135

Iron

Reducediron
absorptionfromthe
gastrointestinal
tractduetolackof
acid.

Reductioninabsorptionofdietary,non
hemeironmayoccur,butanemiais
unlikelywithuseofPPIsforseveral
yearsinpeoplewithnormalironstores.
Supplementsmaybeneededinpeople
withotherfactorscontributingtoiron
deficiency.4483,4539,8850,9578

Dibencozide
VitaminB12

Decreasedgastric
acidreduces
cleavageofprotein
bounddietary
vitaminB12,
reducingthe
amountavailable
forabsorption.

Deficiencyisunlikelyunlessdietary
intakeofvitaminB12ispoor,orPPIsare
takencontinuouslyfor2yearsormore.It
ismorelikelyifthepatientisrendered
achlorhydric.Inthesecircumstances
monitorforvitaminB12deficiencyand
anemia,andconsidersupplementsif
necessary.44836,9513,9528

VitaminC

Preliminarydata
Itisnotknownifthisisclinically
suggests
significant.10572
omeprazole
reducesvitaminC
levels,possiblydue
toincreased
destructionof
vitaminCathigher
gastricpHlevels.

Zinc

Each40mgvialof
pantoprazoleIV
contains1mg
EDTAwhichcan
chelatezinc.

PantoprazoleIV240mg/dayfor7days
increasesurinaryzincexcretion,but
serumzinclevelsare
unchanged.11665 Zincsupplementsare
notusuallynecessarywithtypicaldoses
ofpantoprazoleIV.

Inhibitionofgastric
acidsecretion
mightreduce
absorptionofzinc.

PPIsmightreduceabsorptionofzinc
fromsupplements,11637 butPPIsdon't
seemtoaffectzincabsorptionfrom
food.11638 Clinicallysignificantzinc
depletionhasnotbeenreported.

PhosphateSalts

Sucralfatehas
phosphatebinding
propertiesand
reducesphosphate
absorption.

Dosesof617grams/dayhavebeen
usedtoreduceelevatedphosphate
levelsinpatientswithrenal
failure.14594,14595 Inpeoplewithnormal
renalfunctionthereisariskof
hypophosphatemiaiflargedosesof6
grams/dayormoreareusedfor
prolongedperiods.14595 Ifphosphate
supplementsandsucralfateareneeded
concurrently,separatedosesbyatleast
2hours.

Calcium
VitaminD

Increasedrenal
calciumexcretion
anddecreased

Steroidinducedosteoporosis,andthe
associatedincreaseinfracturerisk,are
wellrecognizedconsequencesoflong

MISCELLANEOUS
Sucralfate

HORMONES
Corticosteroids[Glucocorticoids]:
Shortacting
Cortisone(Cortone),Hydrocortisone[Cortisol](Cortef,Hydrocortone)

Intermediateacting
Prednisone(Deltasone,Meticorten,Orasone,PanasolS),Prednisolone(DeltaCortef,Prelone,Pediapred),Triamcinolone
(Aristocort,Atolone,Kenacort),Methylprednisolone(Medrol)
Longacting
Dexamethasone(Decadron,Dexameth,Dexone),Betamethasone(Celestone)

intestinalcalcium
absorption.This
depletionof
calciumcreatesa
greaterneedfor
vitaminD,to
improvecalcium
absorption.

termadministrationofcorticosteroids,in
dosesequivalenttoprednisone7.5
mg/dayorhigher.Recommendpatients
maintainacalciumintakeof1500
mg/dayandavitaminDintakeof800
units/day.Monitorlevelsandconsider
supplementsifnecessary.1832,44627

Chromium

Increasesrenal
excretionof
chromium.

Chromiumdeficiencymaycontributeto
corticosteroidinducedhyperglycemia.
Theroleofchromiumsupplementshas
notbeenadequatelystudied.5039

FolicAcid

Patientswith
Theclinicalsignificanceofthisisnot
multiplesclerosis
known.9362
treatedwith
methylprednisolone
seemtohave
decreasedserum
folatelevels.

Magnesium

Druginducedbone Serummagnesiumlevelsareusuallynot
lossreleases
affectedandsupplementsarenot
magnesiumfrom
necessary.95079,96289
boneandincreases
urinaryexcretion.

Potassium

Corticosteroids
causesodium
retention,resulting
incompensatory
renalpotassium
excretion.

Strontium

Mightincrease
Theclinicalsignificanceofthisisnot
urinaryexcretionof known.11405
strontium.

Zinc

Shiftofzincfrom
thebloodintothe
tissuesand
possiblyincreased
lossintheurine.

Supplementsareunlikelytobe
necessary.1160611

Possiblyreduced
absorption,
increased
excretion,
increasedprotein
bindingand
inductionofliver
enzymeswhichuse
folate.

Folicacidsupplementsshouldbe
consideredonlyinpeoplewithavery
lowdietaryintake,orwithother
conditionswhichcontributetofolate
deficiency.4459,4498,78434,93713,9532

Estrogens:
FolicAcid
(Alora,Cenestin,Climara,Estinyl,Estrace,Estraderm,Estratab,FemPatch,Menest,Ogen,Premarin,Premphase,Prempro,Vivelle)
EstrogencontainingOralContraceptives

Hypokalemiaisdosedependentand
morecommonwithsteroidshavinghigh
mineralocorticoidactivity
(hydrocortisone,cortisone,
fludrocortisone,prednisone,
prednisolone).Monitorpotassiumlevels
withchronictherapy.Ifnecessary,give
supplements,orswitchtoasteroidwith
nomineralocorticoidactivity
(betamethasone,dexamethasone,
methylprednisolone,triamcinolone).4425

Magnesium

Shiftfromplasmato Monitormagnesiumlevelsinpeoplewith
tissues.
otherriskfactorsfor
hypomagnesemia.9621,963840

Pyridoxine(B6)

Interferencewith
pyridoxine
metabolism.

Reducedplasmapyridoxalphosphate
levelshavebeenreported,butmay
returntonormaldespitecontinued
therapy,especiallywithlowdosesof
estrogen.It'ssuggestedthatpyridoxine
deficiencycontributestodepression,
lethargyandfatigueassociatedwithoral
contraceptives,butthereisnogood
evidencethatsupplements
help.4459,4498,95046,9510

Riboflavin(B2)

Possiblyreduced
absorptionor
interferencewith
conversiontoactive
form.

Reducedriboflavinlevelsreportedin
womenwithlowdietaryintakewhowere
takinghighdoseoralcontraceptives
whicharenolongeravailable.Riboflavin
supplementsarenotnecessarywhen
dietaryintakeis
adequate.4548,9373,9505,105237,10536

Thiamine(B1)

Smallreductionin
Routineuseofthiaminesupplementsis
activityofthe
notnecessary.10548,10555
thiamine
dependentenzyme
erythrocyte
transketolase,
suggestingmild
thiaminedeficiency.

VitaminA

Estrogensstimulate
productionofretinol
bindingprotein,
increasingthe
amountofvitaminA
removedfromliver
storageandcarried
inblood.

VitaminAsupplementsmighthelp
maintainliverstores,buttheneedforthis
hasn'tbeen
proven.9373,9505,10523,10548

Dibencozide
VitaminB12

Reducedprotein
binding,leadingto
increasedtissue
uptake.

VitaminB12supplementsarenot
necessary.4498,4547,7843,9371

Mayreduce
absorption,
increase
breakdown,or
increasevitaminC
requirementsto
preventoxidationof
estrogens.

Dataareconflicting,butdeficiencyis
unlikelyunlessdietaryvitaminCisvery
low.Routinesupplementsarenot
necessary.10548,10583,10585

Decreasesin
serumalbuminmay
reducetheamount
ofzinccarriedin
theblood.There

Dataareconflicting,buttheredoesnot
appeartobeincreasedlossofzincfrom
thebody.Supplementsareprobablynot
necessary.9505,1164251

VitaminC

Zinc

3,9505,10123

7,11161,11528,118756

mayalsobe
increaseduseand
uptakeofzincby
thetissuesdueto
anaboliceffects.
Thyroidhormones:
Levothyroxine(Levothroid,Levoxyl,Synthroid,ThyroTabs,Unithroid)
Thyroiddesiccated(ArmourThyroid)
Liothyroninesodium(Cytomel)

Calcium

Increasedbone
turnovermaylead
toincreasedurinary
calciumlosses.

Calciumlossisunlikelytobeclinically
significantwithdosesofthyroid
hormonesusedtotreathypothyroidism.
Checkthyroidfunctionteststoensure
patientsarenotreceivingexcessive
thyroidhormonedoses,whichmay
increasecalciumlosses.279,2684
5,2695,26978,2721

Teriparatide(Forteo)

PhosphateSalts

Teriparatide
increasesurinary
phosphate
excretionand
decreasesserum
phosphatesimilarly
tohuman
parathyroid
hormone.

Afterasingledoseofteriparatide,serum
phosphatelevelsfallforabout2hours
andthenrecovertobaseline.14590 This
recoveryalsoseemstocontinueeven
withseveralyearsoftreatment,with
patientshavingeithernochangein
serumphosphatelevels,orasmall
decreasewhichdoesnottakethem
belowthenormal
range.14596,14597,14598,14599 Phosphate
supplementsarenotnecessarywith
teriparatide.

Magnesium
Potassium

Intracellularshiftof
magnesiumand
potassium.

Maycontributetoarrhythmias,especially
athighdosesandinpeoplewithother
riskfactors.Monitorelectrolytelevels
duringacuteuseofhighdoses(e.g.,in
pretermlabororacuteasthmaattacks),
andinpeoplewithotherriskfactors.With
chronicuseofbeta2agonists,
electrolytelevelsmayreturnto
baseline.2644,6203,6205,6209

RESPIRATORY
Beta2Agonists:
Albuterol(salbutamol,Proventil,Ventolin),Bitolterol(Tornalate),Isoetharine,Levalbuterol(Xopenex),Metaproterenol(Alupent),
Pirbuterol(Maxair),Salmeterol(Serevent),Terbutaline(Brethine)

10,6217,7001,88806,8889
91,9507,9517,9534,9599,9641

Methylxanthines
Theophylline(Slobid,Theo24,TheoDur,Theolair)
Aminophylline
Oxtriphylline(CholedylSA)
Diphylline(Lufyllin)

Potassium

Possiblyincreased Riskforhypokalemiaisdosedependent.
intracellularuptake. Monitorpotassiumlevelsinpeopleon
highdosesorwithotherrisk
factors.9534,95379

Pyridoxine(B6)

Inhibitsconversion
ofpyridoxinetoits
activeform.

Suggestedthatpyridoxinedeficiency
contributestosideeffectsoftheophylline,
butdataareconflicting.Itisnotclear
whetherthereisanybenefitwith
pyridoxine
supplements.4522,7064,7066,9480,9503

Glutathione

Alcoholdepletes
endogenous
glutathione.

Itisnotknownifglutathionesupplements
wouldbebeneficial.

MISCELLANEOUS
Alcohol

CobaltIrradiation

Dibencozide
VitaminB12

Irradiationofthe
smallbowelcan
decrease
absorptionof
vitaminB12.

Theclinicalsignificanceisunknown.15

Cyclosporine(Neoral,Sandimmune)

Magnesium

Significantlossof
magnesiuminthe
urine,probablydue
toreducedtubular
reabsorptionand
tubulardamage.

Hypomagnesemiamaycontributeto
seizuresandneurotoxicity.Monitor
serummagnesiumlevelsclosely.
Supplementsmaybeneeded,ordose
reduction/discontinuationof
cyclosporine.9117,96323

Deferoxamine(Desferal)

Zinc

Dosedependent
increaseinurinary
zincelimination.

Somepeoplemaintainnormalzinc
levelsduetocompensatorymechanisms
whileothersdonot.Deficiencyisrare,
butmaybelinkedtovisual/hearingloss.
Monitorforzincdeficiencyandgive
supplementsifnecessary.6597,1162831

Disulfiram(Antabuse)

Zinc

Ametaboliteof
disulfiramchelates
zinc,alteringzinc
absorption.

Dosesofdisulfiramuptoabout320
mg/daymaydecreaseintestinalzinc
absorption,whilehigherdosesof400
mg/daymightincreaseit
slightly.11613,11635 Theclinical
significanceofthisisnotclear.

EDTA

Zinc

Chelationofmetal
ions,includingzinc,
leadingto
increasedurinary
excretion.

Inthetreatmentofleadpoisoning,
calciumdisodiumEDTAincreases
urinaryzincexcretion10to17fold,and
decreasesserumlevels40%.Levels
recoverafterasinglecourse,but
repeatedcoursescancausedeficiency.
Thereisconcernthatsupplementsmay
reduceefficacyofEDTAtreatment.Use
onlyifclinicallynecessary.9630,11667
8,11670

Isotretinoin(Accutane,Claravis,AccutaneRoche,Isotrex)

AcetylLcarnitine
Lcarnitine
ProprionylL
carnitine

Notknown.

Reducedcarnitinebloodlevelshave
beenreported,sometimeswith
symptomsofcarnitinedeficiency,such
asmyalgiaandmuscle
stiffness.3619 Otherstudieshavefound
nosignificanteffectofisotretinoinon
carnitinebloodlevels.11557 Thereisnot
enoughinformationtorecommend
routineuseofLcarnitinesupplements
withisotretinoin.

LanthanumCarbonate

PhosphateSalts

Lanthanum
carbonatebinds
phosphateinthe
gutandreduceis
absorption.

Lanthanumcarbonateisused
therapeuticallytoreduceelevated
phosphatelevelsinpatientswithrenal
failure.14588 Avoidlanthanumcarbonate
inpeoplewithnormalphosphatelevels.

Nitrousoxide(N2 O)

Dibencozide
VitaminB12

Inactivatesthe
cobalaminformof
vitaminB12.

Deficiencysymptomsmayoccuraftera
singledoseofnitrousoxideinpeople
withpreexisting,subclinicaldeficiency.
CheckvitaminB12levelsbeforeusing

nitrousoxideanesthesiainpeoplewith
riskfactorsforvitaminB12
deficiency.9527,9532
Orlistat(Xenical)

BetaCarotene
VitaminA
VitaminD
VitaminE
VitaminK

Decreased
absorptionoffat
solublevitamins
fromthe
gastrointestinal
tract.

Vitaminlevelsusuallyremainwithin
normallimits.Themanufactureroforlistat
recommendsallpatientstakea
multivitaminsupplement,separatingthe
dosefromorlistatbyaleast2hours.
Monitorclottingtimescloselyinpatients
takingwarfarinand
orlistat.1727,1730,9595,105701,11520

Sevelamer

PhosphateSalts

Sevelamerbinds
phosphateinthe
gutbyanion
exchange
mechanism.

Sevelamerisusedtoreduceelevated
phosphatelevelsinpatientswithrenal
failure.Avoidsevelamerinpeoplewith
normalphosphatelevels.14588

Sunscreens

VitaminD

Frequentand
extensive
applicationof
sunscreenscan
reducevitaminD
synthesisinthe
skinandplasma
levels.

Usualuseofsunscreenisnotlikelyto
causeclinicallysignificantvitaminD
deficiencyinmostpeople.115079

Tacrolimus(FK506,Prograf)

Magnesium

Reducedrenal
tubular
reabsorptionleads
toincreased
excretionof
magnesium.

Hypomagnesemiaoccursinasignificant
proportionofpatients.Monitorlevelsand
givesupplementsas
necessary.8900,9620

Footnote:OralLcarnitinesupplementationisstronglysuggestedforthefollowinggroups:patientswithcertainsecondarycarnitinedeficiencysyndromessymptomaticVPAassociatedhyperammonemiamultiple
riskfactorsforVPAassociatedhepatotoxicityinfantsandyoungchildrentakingVPA.AnoralLcarnitinedosageof100mg/kg/day,uptoamaximumof2g/dayhasbeenrecommended.