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29MedicationsThatMayCauseAdverseInteractionswithThyroidDrugs
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Thethyroidmedicationlevothyroxine(http://www.worstpills.org/member/drugprofile.cfm?m_id=28)
(LEVOT,LEVOXYL,NOVOTHYROX,SYNTHROID,THYROTABS,UNITHROID)isusedtotreat
hypothyroidism,anendocrinedisorderresultingfromathyroidhomone
(http://www.worstpills.org/member/page.cfm?op_id=9)deficiencythataffectsabout4.6percentofthe
U.S.population.Themedicationisusedtoreplacethemissingordeficientamountofthyroidhormone.
Thenumberofprescriptionsforlevothyroxinefilledeachyearmorethan75millionU.S.prescriptions
in2007makesitoneofthemostprescribeddrugsinthecountry.
Unfortunately,theuseofothermedicationswhiletakinglevothyroxinecouldhaveoneofseveralkindsof
unintendedresults:
Certainmedicationscandecreasetheabsorptionoflevothyroxineresultinginlowerlevelsin
theblood.
Othermedicationscanincreasetherateatwhichthebodygetsridoflevothyroxine,also
resultinginlowerthyroidlevelsintheblood.
Othermedicationscancausechangesoflevothyroxinebindinginblood
Levothyroxinecanaffectthesafetyoreffectivenessofothermedicationsbyraisingorlowering
thelevelsoftheseotherdrugsintheblood.
Druginteractionsthatreduceabsorptionoflevothyroxine
Somedrugsmayinteractwithlevothyroxinebythwartingtheabsorptionofthisthyroiddrug.Thiseffect
canbeavoidedbytakingthyroxineconsiderablybeforeor,insomecases,aftertheotherdrug.That
allowsthelevothyroxinetogetabsorbedwithoutinteractingwiththeseconddrug.
Antacidsoftenusedtotreatheartburn(http://www.worstpills.org/member/page.cfm?op_id=28)andother
intestinaldistress,includingcalciumproducts
(https://www.worstpills.org/member/drugprofile_dietary.cfm?m_id=168)suchasTUMSorROLAIDSand
otherantacids,mayhaveabsorptioninhibitingeffectsonthyroidmedications.Peopleshouldtake
levothyroxinefourtosixhoursbeforeoraftertakingtheseantacids.
Ironsupplements(http://www.worstpills.org/member/drugprofile.cfm?m_id=169)(FEOSOL,SLOWFE)
havebeenshowntoreducetheeffectoflevothyroxineinsomepeople,althoughtheeffectishighly
variablefromonepersontoanother.Otherironpreparationsmayalsohavesimilareffects.Again,we
advisetakingthelevothyroxinefourtosixhoursbeforeoraftertheiron.
Sucralfate(http://www.worstpills.org/member/drugprofile.cfm?m_id=248)(CARAFATE),usedtotreat
ulcersandothergastrointestinaldiseases,appearstoinhibittheabsorptionoflevothyroxine.Trialsfound
thatthisinteractionwasavoidedwhenthethyroiddrugwasgiveneighthoursafterthesucralfate.
Sevelamer(RENAGEL,RENVELA),whichisusedtoreduceexcessivebloodphosphateinpersons
withseverechronickidneydisease,alsointerfereswiththeabsorptionoflevothyroxine.Separatingthe
dosesofthetwotypesofdrugsbyatleastfourtosixhoursislikelytoaverttheinteraction.
Cholestyramine(http://www.worstpills.org/member/drugprofile.cfm?m_id=198)(Questran)lowers
cholesterolbyincreasingtheconversionofcholesteroltobileacids.Butitalsotendstoreduce
levothyroxinesabsorptionandeffect.Similaragentssuchascolestipol(COLESTID)andcholesevelam
(WELCHOL)mayhavethesameeffect,althoughthereisnotasmuchevidenceforthis.We
recommendseparatingallofthesemedications,knownasbileacidbinders,fromthetakingof
levothyroxinebyatleastfourtosixhours.
Theantibioticciprofloxacin(http://www.worstpills.org/member/drugprofile.cfm?m_id=258)(CIPRO)was
associatedwithreducedlevothyroxineeffectincasereports,butmoreinformationisneededtoestablish
whethertheinteractionoccurs.Untilmoreinformationisavailable,itwouldbeprudenttoseparatedoses
ofciprofloxacinfromthoseoflevothyroxinebyatleastfourhours.Thesameprecautionshouldapplyto
otherantibioticsinthesameclass,suchaslevofloxacin
(https://www.worstpills.org/member/drugprofile.cfm?m_id=258)(LEVAQUIN),lomefloxacin

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(https://www.worstpills.org/member/drugprofile.cfm?m_id=258)(MAXAQUIN),monifloxacin(AVELOX),
norfloxacin(NOROXIN),andofloxacin(https://www.worstpills.org/member/drugprofile.cfm?m_id=258)
(FLOXIN).
Raloxifene(http://www.worstpills.org/member/drugprofile.cfm?m_id=68)(EVISTA),usedtotreat
osteoporosis,mayreducetheabsorptionoflevothyroxine,althoughtheevidencetodateisnotsufficient
toestablishtheextentoftheinteraction.Inonecase,separatingthetwodrugsby12hoursappearedto
averttheinteraction.
Drugsthatincreasemetabolismoflevothyroxine,loweringbloodlevels
Enzymeinducersstimulatetheproductionofenzymes,whichinturnincreaselevothyroxinefromthe
body.Inpatientswithnormalthyroidfunction,thebodycompensatesforthisbyproducingmorethyroid
hormone,thusnormalizingthyroidlevels.Butthisfeedbackmechanismisimpairedinthosetaking
levothyroxine,andtheymaynotbeabletorespondappropriately.Theresultisthattheycanmay
becomehypothyroidwhentheytakecertainenzymeinducingdrugsandmayneedanincreaseddoseof
levothyroxinetomakeupforthedeficiency.Followingareseveralcategoriesofenzymeinducersthat
canlowerbloodthyroidlevels:
Antiepilepticdrugsusedtotreatseizuresincludingcarbamazepine
(http://www.worstpills.org/member/drugprofile.cfm?m_id=147)(TEGRETOL),oxcarbazepine
(TRILEPTAL),phenobarbital(https://www.worstpills.org/member/drugprofile.cfm?m_id=151)(LUMINAL,
SOLFOTON),primidone(MYSOLINE),andphenytoin
(http://www.worstpills.org/member/drugprofile.cfm?m_id=152)(DILANTIN)canincreasethe
metabolismoflevothyroxineandwouldrequirelargerdosesofthedrug.
Antimicrobialagentsusedtotreatinfectionsalsomayreducetheeffectoflevothyroxine.Rifampin
(https://www.worstpills.org/member/drugprofile.cfm?m_id=275)(RIFADIN)isapotentenzymeinducer,
andisknowntohaveproducedhypothyroidisminapatientonlevothyroxinetherapy.Thefollowing
antimicrobialsarealsoenzymeinducersandmayhaveasimilareffect:efavirenz(SUSTIVA),nevirapine
(VIRAMUNE),rifabutin(MYCOBUTIN)andrifapentine(PRIFTIN).
St.Johnswort(https://www.worstpills.org/member/drugprofile_dietary.cfm?m_id=299)isalsoan
enzymeinducer.Onestudyfoundthatitmayincreaselevothyroxinemetabolism.Takingthetwodrugs
shouldbeavoided,butifyoudecidetousethecombination,youshouldtellyourdoctorandbeonthe
alertforanysymptomsofhypothyroidism(e.g.,lowenergy,fatigue,depression,dizziness,weightgain
andanemia).
Otherdrugsthatmayincreaseeliminationofthyroidhormoneincludeimatinib(GLEEVEC),whichis
usedtotreatleukemiaandothercancersandmayresultinhypothyroidismwhenusedtogetherwith
levothyroxine.
Theselectiveserotoninreuptakeinhibitor(SSRI)sertraline
(https://www.worstpills.org/member/drugprofile.cfm?m_id=53)(ZOLOFT),widelyprescribedfor
depression(https://www.worstpills.org/member/page.cfm?op_id=22),hasbeenassociatedwitha
decreaseintheeffectoflevothyroxine.Furtherstudiesareneededonthis,andonanysimilareffectsof
otherSSRIs.
Interactionsthatresultinchangesoflevothyroxinebindinginblood
Thyroxinebindingglobulin(TBG)isaproteinthatbindstoandcarriesthyroidhormoneinthe
bloodstream.WhenthelevelofTBGishigh,levothyroxineistrappedinthebloodstreamandcannotget
intothetissueswhereitisneeded.Ifthethyroidisfunctioningproperly,itwillcompensateforthisby
producingmorethyroidhormones.Butifthethyroidisimpairedasisthecaseformostpeopletaking
levothyroxineanincreaseinTBGinducedbyanotherdrugmayproducesymptomsof
hypothyroidismbecausethethyroidcannotproducemorehormone.
EstrogensincreaseTBG,andwomenwhoaretakingthematthesametimetheyareonlevothyroxine
mayneedtoincreasetheirdoseofthelatter.Transdermalestrogenreplacement
(https://www.worstpills.org/member/drugprofile.cfm?m_id=37)(viapatch)doesnothavemucheffecton
TBG,sothismaybepreferableforwomentakinglevothyroxine.Oralcontraceptives
(http://worstpills.org/member/page.cfm?op_id=7)containingestrogens(whetheroralorviapatch)
increaseTBGandmayincreaseawomanslevothyroxinerequirements.
Effectsoflevothyroxinewithwarfarin(COUMADIN)
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Warfarin(http://www.worstpills.org/member/drugprofile.cfm?m_id=216)(COUMADIN)caninteractwith
levothyroxine,buttheresultscanrangefromnegligibletolifethreatening.Whenapersonsthyroid
functionistoohigh,thewarfarinsanticoagulanteffectswillbemagnifiedandanormaldoseofwarfarin
willthereforecausethebloodtobetoothinandmaycausebleeding.Conversely,apersonwhose
thyroidfunctionistoolowwillnotrespondnormallytotheanticoagulant,willbesomewhatwarfarin
resistant,andthebloodwillnotbethinenough,thatis,willclottooeasily.
Thosewhoareonstable,appropriatedosesofbothwarfarinandlevothyrozineshouldbeallrightas
longastheirthyroidfunctionisstableandthemeasureofbloodthinning,theINR,isinthenormalrange.
Butthosewhoarefirstonwarfarinandthenlaterstartonlevothyroxineruntheriskofamagnifiedeffect
ofwarfarin,whichcanresultindangerousbleeding.Inthiscase,thepatientislikelytoalreadybeona
largedoseofwarfarinbecausethehypothyroidismhasrenderedthemsomewhatwarfarinresistant.
Whenthehypothyroidismiscorrectedbythelevothyroxinethewarfarinresponsereturnstonormaland
thebloodbecomestoothinlifethreateningbleedinghasoccurredfromthisseriesofevents.
Inordertoavoidsuchharmfulinteractions,patientsneedtoknowthattheirthyroidstatuscanaffecttheir
warfarinrequirements.Morefrequentbloodtestswhenstartinglevothyroxinecanmonitorapersons
responsetotheanticoagulant,allowingpromptadjustmentsasneeded.
Patientstakingbothwarfarinandlevothyroxineandarealreadystabilizedwhothentakeanotherdrug
thatreducesthelevothyroxineeffect(asdiscussedabove),mayhavetheanticoagulantseffect
decreaseandthusbeatincreasedriskofdevelopingabloodclot.

Inshort
Levothyroxineinteractionsarecommonlyencounteredinmedicalpracticebecauselevothyroxineis
widelyprescribedasaremanyotheroftheinteractingdrugs.Butpropertestinganddosageadjustments
canpreventadverseoutcomes.Thosetakinglevothyroxinemustbeawareoftheseinteractions,and
takeremedialactionbeforeanysideeffectsoccur.
Table.Drugsthatinteractwithlevothyroxine
Interactionsthatresultinreducedlevothyroxineabsorption
CALCIUMPRODUCTS
calciumcarbonate(TUMS)
calciumcarbonateandmagnesiumhydroxide(ROLAIDS)
OTHERANTACIDS
aluminumhydroxide(AMPHOJEL)
ironsupplements
ferroussulfate(FEOSOL,SLOWFE)
OTHERDRUGS
cholesevelam(WELCHOL)
cholestyramine(LOCHOLEST,QUESTRAN,QUESTRANLIGHTQUESTRAN)**
raloxifene(EVISTA)**
sevelamer(RENAGEL,RENVELA)
sucralfate(CARAFATE)**
FLUOROQUINOLONEANTIBIOTICS
ciprofloxacin(CIPRO)
levofloxacin(LEVAQUIN)**
lomefloxacin(MAXAQUIN)**
moxifloxacin(AVELOX)*
norfloxacin(CHIBROXIN,NOROXIN)**
ofloxacin(FLOXIN)**
GrapefruitJuice
Interactionsthatresultinincreasedlevothyroxinemetabolism,lowerlevelsofintheblood
ANTIEPILEPTICDRUGS
carbamazepine(CARBATROL,TEGRETOL)
oxcarbazepine(TRILEPTAL)
phenobarbital(LUMINAL,SOLFOTON)**
phenytoin(DILANTIN)
primidone(MYSOLINE)

ANTIMICROBIALAGENTS
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efavirenz(SUSTIVA)
nevirapine(VIRAMUNE)
rifabutin(MYCOBUTIN)
rifampin(RIFADIN,RIMACTANE)
St.Johnswort
OTHERDRUGS
imatinib(GLEEVEC)
sertraline(ZOLOFT)**
Interactionsthatresultinchangesoflevothyroxinebindinginblood
Estrogens
Interactionthatresultsinincreasedordecreasedlevelsofotherdrugs
warfarin(COUMADIN)
*DoNotUseinWorstPills,BestPills
**LimitedUseinWorstPills,BestPills

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