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CommonlyUsedGout,KidneyStoneDrugTooDangerousforUnprovenUses
WorstPillsBestPillsNewsletterarticleFebruary,2016

Formostpatientssufferingfromgout,allopurinol(LOPURIN,ZYLOPRIM)isafirstlinetherapy:By
reducinghighuricacidlevelsintheblood,thedrugpreventssuddenattacksofdisablingjointpainand
swelling,progressivejointdamage,andothergoutcomplications.Thedrugalsoisacornerstoneof
treatmentforpatientswithkidneystonescausedbyhighlevelsofuricacidintheurine.
Althoughallopurinolhasseriousrisks,thesegenerallyareoutweighedbyitsbenefitswhenusedtotreat
thesetwodisorders.
Overthepastseveralyears,physiciansincreasinglyhaveprescribedthedrugforausenotapproved
bytheFoodandDrugAdministration(FDA):toreducehighblooduricacidlevelsinpeoplewithoutany
signsorsymptomsofgoutorkidneystonesbutwhohaveaconditionknownasasymptomatic
hyperuricemia.[1]However,thereisevidencethattherisksofallopurinolforthisofflabeluseoutweigh
thebenefits.Infact,theFDAapprovedlabelforallopurinolstates:
Thisisnotaninnocuousdrug.Itisnotrecommendedforthetreatmentofasymptomatic
hyperuricemia.[2]
ASeptember2015studyinJAMAInternalMedicinerevealsthatuseofallopurinoltolowerhighblood
uricacidlevelsinpeoplewithoutsymptomsclearlyisassociatedwithanalarmingincreaseintheriskof
lifethreateningskinreactions,aknowndangerofthedrugingoutandkidneystonepatients.These
findingsreinforcetheadviceinthedrugslabelwarningagainstsuchuse.
Uricacidrelatedillness
Uricacidisasubstanceproducednaturallyinthebody.Itisfilteredoutofthebloodbythekidneysand
removedfromthebodythroughtheurine.Toomuchuricacidintheblood,whichcanbemeasuredbya
routinebloodtest,mayleadtodepositsofuricacidcrystalsinjointsandothertissues,resultingingout
attacks.Likewise,toomuchuricacidintheurinemaycausecrystalformationinthekidney,whichcan
leadtokidneystonesorrenalfailure.
Allopurinolblocksthebodysproductionofuricacid,therebydecreasingbloodandurinelevelsofthe
substance.Thegoaloftreatmentforgoutandkidneystonepatientsistoreduceuricacidconcentrations
inthebloodandurine,respectively,tolevelsbelowthoseneededforcrystalformation.
Importantly,abouttwothirdsofpeoplewithhighbloodlevelsofuricacidnevergoontodevelopgoutor
uricacidrelatedkidneystones.[3]Nevertheless,somedoctorsprescribeallopurinoltopeoplewhohave
asymptomatichyperuricemiabecausetheconditionisassociatedwithotherdiseasesunrelatedtouric
acidcrystalformation,includinghypertension,heartdiseaseandprediabetes.[4],[5]Suchtreatmentis
controversialbecausehighuricacidhasneverbeenshowntocausethesediseases,[6],[7]whereas
allopurinolisknowntocausedangeroushypersensitivityreactions.
Hypersensitivityreactions
Theseallergiclikereactionscandevelopwithinseveralweeksofstartingallopurinol.Themost
prominentsymptomoftheseadversereactionsisasevererash.Therashoftenappearsaslargered
blotchesthatcanprogresstocoverlargeportionsoftheskin.Inthemostseveretypesof
hypersensitivityreactions,patientsdevelopblisters,andskinsubsequentlysloughsoff.Suchcases
resemblesevereburns.
Theskinrashisoftenaccompaniedbysimilarlesionsinthemouth,aswellassymptomsofsystemic
illness,suchasfever,fatigue,andmuscleandjointpains.Damagetointernalorgans,suchastheliver
andlungs,alsocanoccur.

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TheJAMAInternalMedicinestudyshedsnewlightonthefrequencywithwhichallopurinolisbeingused
forasymptomatichyperuricemiaandtheunacceptableriskthisposestopatients.
Thenewstudy[8]
AteamofresearchersinTaiwanwantedtolearnwhydoctorsprescribeallopurinoltopatientsandhow
oftenthesepatientsdeveloppotentiallyfatalhypersensitivityreactions.Toanswerthesequestions,they
examinedmedicalrecordsstoredinanationaldatabasethatcovers23millionpeoplenearlyallofthe
countryspopulationunderTaiwansnationalhealthinsuranceprogram.
Theresearchersidentifiedallpatientswhowerestartedonallopurinolfrom2005through2011(about
496,000people).Overthesevenyearstudyperiod,43percentofthesepatientswereprescribedthe
drugforhighblooduricacidlevelswithouthavingsymptomsofillness.Thispercentagesteadilyrose
from37percentin2005to50percentin2011.
Overtheentirestudyperiod,approximatelyoneofevery200allopurinoltreatedpatientsdeveloped
hypersensitivityreactionswithinthreemonthsofstartingthedrug.Ofthese,morethan40percent
requiredhospitalizationwithinonemonthofdevelopingthereaction,and8percentdiedwithintwo
months.Theinvestigatorsalsofoundthattheincidenceofallopurinolinducedhypersensitivityreactions
steadilyincreasedfrom2005to2011,dueinparttotheincreaseduseofthedrugforasymptomatic
hyperuricemia.
Strikingly,theresearchersfoundthattreatmentwithallopurinolforasymptomatichyperuricemiadoubled
theriskofhavingordyingfromahypersensitivityreaction,comparedwithpatientswhoweretakingthe
drugforgoutorothersymptomaticuricacidcausedillnesses.
IntheU.S.,theincidenceofallopurinolhypersensitivityreactionsisaboutonefourththatseenin
Taiwan,whichmeansaboutoneofevery1,000U.S.patientstreatedwithallopurinoldevelopthese
reactions.[9]ThisdifferenceisdueinparttothefactthatmanypeopleinTaiwan,becauseoftheir
Chineseheritage,carrygenesthatmakethemmoresusceptibletosuchdrugreactions.[10]
Nevertheless,thenewstudyresultsareimportanttopatientsintheU.S.becauseevena1in1,000
chanceofhavingapotentiallyfatalhypersensitivityreactionrepresentsanunacceptableriskforpatients
prescribedbutderivingnoprovenbenefitfromallopurinolforasymptomatichyperuricemia.
WhatYouCanDo
Donottakeallopurinolforasymptomatichyperuricemia.Ifyouaretakingthedrugbuthavenotbeen
diagnosedwithgout,uricacidrelatedkidneystonesorrenaldisease,talktoyourdoctoraboutstopping
thedrug.Ifyouaretakingallopurinolforanappropriatemedicalreason,bealertforskinsymptomsand
contactyourdoctorimmediatelyifyoudevelopaskinrash,hivesoritching.
References
[1]YangCY,ChenCH,DengST,etal.Allopurinoluseandriskoffatalhypersensitivityreactions:A
nationwidepopulationbasedstudyinTaiwan.JAMAInternMed.2015175(9):15501557.
[2]DailyMed.DruglabelforZyloprim.UpdatedNovember2009.
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=342832b51a324beabc49
ab0fd152154e&audience=professional(http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?
setid=342832b51a324beabc49ab0fd152154e&audience=professional).AccessedNovember6,
2015.
[3]BeckerMA.Asymptomatichyperuricemia.LastupdatedFebruary5,2015.UpToDate.
http://www.uptodate.com/contents/asymptomatichyperuricemia?
source=search_result&search=asymptomatic+hyperuricemia&selectedTitle=1~24
(http://www.uptodate.com/contents/asymptomatichyperuricemia?
source=search_result&search=asymptomatic+hyperuricemia&selectedTitle=1~24).Accessed
November6,2015.
[4]Ibid.
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[5]YangCY,ChenCH,DengST,etal.Allopurinoluseandriskoffatalhypersensitivityreactions:A
nationwidepopulationbasedstudyinTaiwan.JAMAInternMed.2015175(9):15501557.
[6]Ibid.
[7]BeckerMA.Asymptomatichyperuricemia.LastupdatedFebruary5,2015.UpToDate.
http://www.uptodate.com/contents/asymptomatichyperuricemia?
source=search_result&search=asymptomatic+hyperuricemia&selectedTitle=1~24
(http://www.uptodate.com/contents/asymptomatichyperuricemia?
source=search_result&search=asymptomatic+hyperuricemia&selectedTitle=1~24).Accessed
November6,2015.
[8]YangCY,ChenCH,DengST,etal.Allopurinoluseandriskoffatalhypersensitivityreactions:A
nationwidepopulationbasedstudyinTaiwan.JAMAInternMed.2015175(9):15501557.
[9]SternRJ.Editorsnote:Reducinglifethreateningallopurinolhypersensitivity.JAMAInternMed.
2015175(9):1558.
[10]Ibid.

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