Natural Medicines Comprehensive Database 2010

DrugInfluencesonNutrientLevelsandDepletion
ThischartwasdownloadedfromtheNutrientDepletionCheckerinApril2010.Thisinformationchanges
frequently.TogetthemostupdatedinformationclickheretoruntheNutrientDepletionChecker.
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.
helpful.98,10366,115889
Zinc
Increasedurinary
excretion.
Levelsusuallyreturntonormalwithin24
48hoursafteradose.116223
Cyclophosphamide(Cytoxan,Neosar)
VitaminE
Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.
helpful.98,10366,115889
CytosineArabinoside(CytosarU)
VitaminE
Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.
Theclinicalsignificanceisunknown
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.
helpful.98,10366,115889
Etoposide(Etopophos,VePesid,Toposar)
VitaminE
Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.
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.
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.
helpful.98,10366,115889
FolicAcid
Folateantagonist,
preventing
conversionoffolic
acidtoitsactive
form.
Folicacidsupplementscaninterferewith
theactionsofmethotrexate.Avoid,
unlessrecommendedbyan
oncologist.9420
VitaminE
Highdosesof
chemotherapy
seemstoreduce
levelsofvitaminE.
Theclinicalsignificanceisunknown,but
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
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
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
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
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.
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.
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.
notknownifvitaminEsupplementatsare
beneficial.115748
VitaminK
Inductionofliver
enzymesmay
increasevitaminK
metabolism,
Increasedriskofneonatalintracranial
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.
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.
VitaminE
Childrentaking
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
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
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.
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)
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
Chromium
Increasesrenal
excretionof
chromium.
Chromiumdeficiencymaycontributeto
corticosteroidinducedhyperglycemia.
Theroleofchromiumsupplementshas
notbeenadequatelystudied.5039
FolicAcid
Patientswith
multiplesclerosis
known.9362
treatedwith
methylprednisolone
seemtohave
decreasedserum
folatelevels.
Magnesium
Druginducedbone Serummagnesiumlevelsareusuallynot
lossreleases
affectedandsupplementsarenot
magnesiumfrom
boneandincreases
urinaryexcretion.
Potassium
Corticosteroids
causesodium
retention,resulting
incompensatory
renalpotassium
excretion.
Strontium
Mightincrease
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
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
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
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.

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DrugInfluencesonNutrientLevelsandDepletion

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