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1 CanadianFamily VOL 52:NOEMBER • NOE
CanadianFamily VOL 52:NOEMBER • NOEMBRE 2006 CME Approach to managing patients with sulfa allergy Use of antibiotic and nonantibiotic sulfonamides David Ponka, This article has been peer reviewed. Cet article a fait l’objet d’une révision par des pairs. Can Fam Physician 2006;52:1434-1438. Cross-reactivityrare, sulfonamide» étude VOL 52:NOEMBER • NOEMBRE 2006 CanadianFamily • LeMédecindefamillecanadien 1435 Approach to managing patients with sulfa allergy CME Case description MrsMacDonald,70-year-oldwoman,isrelativelynewtomypractice.Sherecentlyhelpedmereviewallergy.”(Patient’snameandagehavebeenchangedtopro privacy.) calhistoryofhypertension,obstructivesleepapnea,osteoarthritis,andmultipleallergies,includingto“sulfa”drugs,hydrochlorothiazide,andvariousenvi ronmentalelementsforwhichshereceivedallergy twicedaily,and81mgofacetylsalicylicacidtakendaily.Hersleepapneawaswellcontrolledwithnightly O.signsofleft-orright-sidedheartfailure.Shecom radiographicandechocardiographicfindings,con -rmedAfterexplainingthediagnosisandherpredisposi tiontoit,prescribed40mgoforalfurosemidetobetakenoncedailyandaskedhertostoptakingsulindac,thinkingitwascontributingtouidreten tion.alsoswitchedhernondihydropyridinecal contributeslesstouidretention.receivedtele phonecallfromthepharmacistlaterthatday,how ever, cations.Althoughfurosemideindeedcarriessulfamoiety,havenotinthepasthesitatedtoprescribeittopatientswhoareallergictosulfaantibioticsbecausethoughtcross-reactivitywasv

2 eryunlikely.reportedprevious“seriou
eryunlikely.reportedprevious“serious”reactiontohydrochlo rothiazide(anothersulfonamidenonantibiotic),so Examining the evidence further,allergy.Thisandsimilarquestionsarisecommonlyinprimarycare, arealsousedfor Pneumocystis cariniiprophylaxisforpatientswithHIVandAIDS.Itissurprising,therefore, - cussed. Sources of information pharmacologyandthemanufacturer’spackageinsertforLasix(furosemide).Althoughthetextbookswereprovide ufacturer’spackageinsertsimplystatedthatpatients amides”withoutfurtherdiscussionordifferentiation“sulfonamide”and“drugsensitivity”from1966tothemydecision.Althoughrandomizedcontrolledtrialarticlesandreportsofconsensusopinion(levelIIIevi surprisingly,primarystudiesthatdealtwithmyquestion.Mostof -vationalstudy(levelIIevidence). Main message Sulfonamidesarecommonlyusedinprimarycare.Althoughtrimethoprim-sulfamethoxazoleandothersulfa-antibioticcombinationsareespeciallywidelyused(sulfonamidesweretherstantibioticseverintroducedin1936),thisclassofmedicationalsoincludesmanynon antibioticagents. Table 1 liststhemostcommondrugscontainingsulfa(SO 2 NH moietyinCanada.Severalofthesedrugsarerarelythoughtofassulfonamides.Adversereactionstosulfaantibioticsarerelatively crobialagents.Adversereactionshavebeenestimated hypersensitivity. Unfortunately,threatening.Theyincludeimmediate,immunoglobulinE–mediatedanaphylacticreactionsandfloridderma tologicreactions,suchasStevens-Johnsonsyndrome.Hypersensitivityreactionsaremorecommonlycharac -terizedbyfeveroramaculopapula

3 rrashthatdevelops7to14daysafterinitiatin
rrashthatdevelops7to14daysafterinitiatingtheoffendingagent. allergy.Thereareimportantchemicaldifferencesbetween tions,andthatthechemicaldifferencesbetweensulfa Dr Ponka is an Assistant Professor and Unit Residency Program Director at the Civic Campus site of the Department of Family Medicine at the University of Ottawa in Ontario. CanadianFamily VOL 52:NOEMBER • NOEMBRE 2006 CME Approach to managing patients with sulfa allergy extremelyunlikely. 1-3Thereisonlyonecasereportin prove moiety. PerhapsthemostreassuringevidencecomesfromStrometal, whoelegantlyturnedtheUnitedKingdomGeneralPracticeResearchDatabaseintoretrospec tivecohortstudy(levelIIevidence)toshowthatgivingsulfanonantibioticstopatientswithhistoryofsulfa(antibiotic)allergycarrieslittleriskofcross-reactivity.Theauthorsreviewedthechartsof969patientswhohadhadallergicreactionstosulfonamideantibioticsandof19 257patientswhohadnot.Allthesepatientssub study,“allergy”wasdenedverybroadlyandincludeddevelopmentofeczemaandvariousunspeciedadverseeffectswithinfullmonthofreceivingthemedicationinquestion,makingunderreportingbiasunlikely.AlthoughStromandcolleaguesfoundthatpatientsallergictosul fonamideantibioticsweremorelikelythannonallergicpatientstoreacttosulfonamidenonantibiotics(9.9%vs1.1%),theyalsofoundthattherateofreactionwasevengreateramongpatientsallergictopenicillinwhoreceivedsulfonamidenonantibiotics(14.2%).Penicillinsdonothavesulfonamidemoiety,sotheresearchersarguedthatanysulfonamidecross-reactivityappearspredomi nantlyrelatedtog

4 reaterpredispositiontoallergicreac tions
reaterpredispositiontoallergicreac tionsingeneralamongpatientsallergictosulfonamideantibiotics,ratherthantospecificsulfahypersensitivity.case,patient’sdrugsandhydrochlorothiazidewerenotwelldocu thespecicnatureofthereactions.Sincethepatientthoughtthatherreactionswereserious,andbecause furosemide.Alookat Table 1arethepotassium-sparingdiuretics(triamterene,spi ronolactone, time, izedthatitdidnothavethesamenatriureticeffectascase,sheneededclosefollow-upasshewasalsotakinganangiotensin-convertingenzymeinhibitor.Somemightarguethatspironolactone,potassium-sparingagentwithstronganti-aldosteroneactivity,wouldbepref erablebasedonthelandmarkRandomizedAldactone improvedpatientswithsevere(classIIIorIV)congestiveheartfailureusingit.Mypatient,however,didnothavethis(10mgbymouthdaily),MrsMacDonalddevelopedtime,however,mypatientisnowdoingwellonthismedicationatdoseof50mgdailyandisnolongercomplainingof Conclusion Thiscaseandtheliteraturereviewdidforitillustratethat,althoughcross-reactivitybetweensulfaantibioticsandnonantibioticsisrare,certainsituationswarrantprudence.difcultdecisionwouldawaitherphysi cianshouldMrsMacDonald’sconditiondeteriorate.Wouldfurosemidecontinuetobecontraindicatedifshedevelopedacutepulmonaryedema?Aftersomereflectionanddiscussionwithmypatient,believethat,consideringherhistoryofseriousreactiontohydrochlorothiazide,allpossiblealternativesshouldbeexploredbeforeusinganothersulfonamidediuretic,suchasfurosemide.Alternativeswouldincludeusingparenteralethacrynicacidandbilevelpositive airwaypressurem

5 ask. Table 1. Commonly used sulfonamide
ask. Table 1. Commonly used sulfonamide nonantibiotic medications available in Canada DIURETICS Carbonic anhydraze inhibitors (Acetazolamide) Loop diuretics • Furosemide • Bumetanide Note that ethacrynic acid is not a sulfonamide Thiazide and related diuretics • Hydrochlorothiazide • Chlorothiazide • Chlorthalidone • Indapamide • Metolazone Glyburide Chlorpropamide Gliclazide Glimepiride Tolbutamide RHEUMATOLOGIC AGENTS Sulfasalazine Probenecid (also commonly used to prolong the half-life of certain antibiotics) Celecoxib Valdecoxib Note that rofecoxib, currently unavailable in Canada, is not a sulfonamide OTHER AGENTS Sumatriptan Naratriptan Topiramate Ibutilide Sotalol Dapsone CanadianFamily VOL 52:NOEMBER • NOEMBRE 2006 CME Approach to managing patients with sulfa allergy indocumentingandreportingallergicreactionsproperlyandinanticipatingpossibleclinicaldilemmasinpatientswithmultipledrugallergies. Competing interests None declaredCorrespondenceto: Dr David Ponka, Department of Family Medicine, Civic Campus Site, University of Ottawa, 210 Melrose Ave, Ottawa, ON K1Y 4K7; telephone 613 761-4334; fax 613 761-4200; e-mail dponka@ottawa - eferencesAJ,DJ,S, N Engl J MedTilleshypersensitivity. Immunol Allergy Clin N JP, Ann PharmacotherWednerHJ,DD. -mide. J Allergy Clin ImmunolTJ,furosemide, thiazide, editor. Basic and clinical pharmacol - ogy.York,NY: B,F,WJ,Investigators. N Engl J Med Tilles South Med J  FOR PRESCRIBING INFORMATION SEE PAGE