Logo
Prev
Bookmark
Rotate
Print
Next
Contents
All Pages
Related Articles
Browse Issues
Help
Search
Home
'
National Geographic : 2002 Apr
Contents
FLONASE® BRIEFSUMMARY (fluticasone propionate) Nasal Spray, 50 mcg SHAKEGENTLY ForIntranasal UseOnly. BEFOREUSE. Thefollowingis a briefsummaryonly;seefullprescribinginformation forcompleteproductinformation. CONTRAINDICATIONS: FLONASE NasalSprayis contraindicated inpatientswitha hypersensitivity toany ofitsingredients. WARNINGS: Thereplacement ofa systemiccorticosteroid withatypicalcorticosteroid canbeaccompanied by signsofadrenalinsufficiency, andinadditionsomepatientsmayexperience symptoms ofwithdrawal, e.g., jointand/ormuscularpain,lassitude,anddepression. Patientspreviouslytreatedforprolongedperiodswith systemiccorticosteroidsandtransferredtotopicalcorticosteroids shouldbecarefullymonitoredforacute adrenalinsufficiencyin responseto stress.In thosepatientswhohave asthmaor other clinical conditionsrequiringlong-termsystemiccorticosteroidtreatment,too rapida decreasein systemic corticosteroids maycausea severeexacerbation oftheirsymptoms. Theconcomitant use of intranasalcorticosteroidswithotherinhaledcorticosteroidscouldincrease theriskofsignsorsymptoms ofhypercorticism and/orsuppression ofthe HPAaxis. Patientswho are on immunosuppressant drugs are moresusceptibleto infectionsthan healthy individuals. Chickenpox and measles,for example,can havea moreseriousor evenfatalcoursein patientson immunosuppressant doses of corticosteroids. In such patientswhohave not had these diseases,particularcareshouldbe takento avoidexposure.Howthe dose,route,and durationof corticosteroidadministration affectsthe riskof developing a disseminatedinfectionis notknown.The contribution oftheunderlyingdiseaseand/orpriorcorticosteroid treatmenttothe riskisalso notknown. Ifexposedtochickenpox, prophylaxis withvaricella zosterimmuneglobulin(VZIG)maybeindicated.Ifexposed to measles,prophylaxiswith pooledintramuscularimmunoglobulin(IG)may be indicated.(See the respectivepackageinsertsforcompleteVZIGandIGprescribinginformation.) Ifchickenpox develops, treatmentwithantiviral agentsmaybeconsidered. PRECAUTIONS: General:Rarely,immediatehypersensitivity reactionsorcontactdermatitis mayoccuraftertheadministration ofFLONASE NasalSpray.Rareinstancesofwheezing, nasalseptumperforation, cataracts,glaucoma,and increasedintraocular pressurehavebeenreportedfollowingthe intranasalapplication of corticosteroids, includingfluticasone propionate. Useofexcessivedosesofcorticosteroids mayleadt signsorsymptms ofhypercorticism, suppression of HPAfunction,and/orreductionof growthvelocityin childrenor teenagers.Physicians shouldclosely followthegrowthof childrenandadolescentstakingcorticosteroids, byany route,andweighthebenefits ofcorticosteroid therapyagainstthepossibility ofgrowthsuppression ifgrowthappearsslowed. Althoughsystemiceffectshave beenminimalwithrecommendeddoses ofFLONASE NasalSpray, potentialriskincreaseswithlargerdoses.Therefore, largerthanrecommended dosesofFLONASE NasalSpray shouldbeavoided. Whenusedat higherthanrecommended doses,orinrareindividuals at recommended doses,systemiccor ticosteroideffectssuchas hypercorticism andadrenalsuppressionmayappear.Ifsuchchangesoccur,the dosageof FLONASE NasalSprayshouldbediscontinued slowlyconsistentwithacceptedprocedures fordiscontinuing oralcorticosteroid therapy Inclinicalstudieswithfluticasonepropionate administeredintranasally, the development of localized infections ofthe noseandpharynxwithCandidaalbicanshasoccurredonlyrarely.Whensuchan infection develops,it mayrequiretreatmentwithappropriatelocaltherapyand discontinuation of treatmentwith FLONASE NasalSpray.PatientsusingFLONASE NasalSprayoverseveralmonthsorlongershouldbeexamined periodically forevidenceofCandidainfectionorothersignsofadverseeffectsonthenasalmucosa. FLONASE NasalSprayshouldbeusedwithcaution,ifat all,inpatientswithactiveorquiescenttuber culousinfection;untreatedlocalorsystemicfungalor bacterial,or systemicviralinfections or parasitic infection; orocularherpessimplex. Becauseoftheinhibitory effectofcorticosteroids onwoundhealing,patientswhohaveexperienced recent nasalseptalulcers,nasalsurgery,or nasaltraumashouldnot use a nasalcorticosteroiduntilhealing hasoccurred. Information forPatients:PatientsbeingtreatedwithFLONASE NasalSprayshouldreceivethe following information andinstructions. Thisinformation is intendedtoaidtheminthe safeand effectiveuseofthis medication.isnotadisclosureofallpossibleadverseorintendedeffects. Patientsshouldbewarnedto avoidexposureto chickenpox or measlesand,if exposed,to consult theirphysicianwithoutdelay. PatientsshoulduseFLONASE NasalSprayat regularintervals as directedsinceitseffectiveness depends onitsregularuse.Adecreasein nasalsymptoms mayoccuras soonas 12hoursafterstartingtherapywith FLONASE NasalSpray.Resultsin severalclinicaltrialsindicatestatisticallysignificantimprovement withinthe firstdayortwooftreatment;however, thefullbenefitofFLONASE NasalSpraymaynotbeachieveduntiltreat menthasbeenadministered forseveraldays.Thepatientshouldnotincreasetheprescribeddosagebutshould contactthephysician if symptoms donotimproveorifthecondition worsens.Forthe properuseofthenasal sprayandtoattainmaximumimprovement, thepatientshouldreadandfollowcarefullytheaccompanying patient'sinstructions. DrugInteractions: Ina placebo-controlled, crossover studyin8healthyvolunteers, coadministration ofa sin gledoseoforallyinhaledfluticasone propionate(1000mcg,5 timesthemaximum dailyintranasaldose)with multipledosesof ketoconazole (200mg)tosteadystateresultedinincreasedmeanfluticasone propionate concentrations, a reductioninplasmacortisolAUC,and noeffectonurinaryexcretionof cortisol.This interaction maybedueto an inhibition ofthecytochrome P4503A4isoenzyme systembyketoconazole, which is alsothe routeof metabolismof tiuticasone propionate.Nodrug interactionstudieshavebeen conductedwithFLONASE NasalSpray;however,careshouldbe exercisedwhenfluticasonepropionate iscoadministered withlong-termketoconazole andotherknowncytochrome P4503A4inhibitors. Carcinogenesis, Mutagenesis,Impairment of Fertility:Fluticasonepropionatedemonstratedno tumorigenicpotentialin miceat oraldosesupto 1000mcg/kg(approximately 20 timesthe maximum recommended dailyintranasaldoseinadultsandapproximately 10timesthemaximumrecommended daily intranasaldosein childrenona mcg/m'basis)for78weeksorin rats at inhalation dosesupto 57mcg/kg (approximately 2 timesthe maximumrecommendeddailyintranasaldosein adultsand approximately equivalent tothemaximum recommendeddailyintranasaldoseinchildrenona mcg/m'basis)for104weeks. Fluticasone propionatedidnot inducegene mutationin prokaryoticor eukaryoticcellsin vitro.No significant clastogenic effectwasseen in culturedhumanperipherallymphocytes in vitroor inthemouse micronucleus testwhenadministered athighdosesbytheoralorsubcutaneous routes.Furthermore, thecom pounddidnotdelayerythroblastdivisioninbonemarrow. Noevidenceofimpairment offertilitywasobservedinreproductive studiesconductedinmaleandfemale rats at subcutaneous dosesup to 50mcg/kg(approximately 2 timesthe maximumrecommendeddaily intranasaldosein adultsona mcg/m'basis).Prostateweightwassignificantly reducedat a subcutaneous dose of50mcg/kg. Pregnancy:Teratogenic Effects:PregnancyCategoryC.Subcutaneous studiesinthemouseandratat45and 100mcg/kg,respectively(approximately equivalentto and 4 timesthe maximumrecommendeddaily intranasaldosein adultsona mcg/m'basis,respectively)revealedfetaltoxicitycharacteristicofpotent corticosteroid compounds, including embryonicgrowthretardation, omphalocele, cleftpalate,andretarded cranialossification. Inthe rabbit,fetalweightreductionandcleftpalatewereobservedat a subcutaneous doseof4 mcg/kg (lessthanthemaximum recommended dailyintranasaldoseinadultsona mcg/m 2 basis). However, noteratogenic effectswerereportedatoraldosesupto300mcg/kg(approximately 25timesthe maximumrecommendeddailyintranasaldosein adultson a mcg/m'basis)offluticasonepropionateto therabbit.Nofluticasonepropionate wasdetectedintheplasmainthisstudy,consistentwiththeestab lishedlow bioavailability followingoraladministration (see CLINICAL PHARMACOLOGY sectionof full prescribinginformation). FLONASE® (fluticasone propionate)NasalSpray,50mcg Fluticasone propionate crossedthe placentafollowing oraladministration of 100 mcg/kgto rats or 300 mcg/kgto rabbits(approximately 4 and25 times,respectively, the maximumrecommendeddaily intranasaldoseinadultsona mcg/m 2 basis). Thereare noadequateand well-controlled studiesinpregnantwomen.Fluticasone propionate should beusedduringpregnancy onlyif thepotentialbenefitjustifiesthepotentialrisktothefetus. Experience withoralcorticosteroids sincetheirintroduction inpharmacologic, asopposedtophysiologic, dosessuggeststhatrodentsare moreproneto teratogenic effectsfromcorticosteroids thanhumans.In addition,becausethereis a naturalincreasein corticosteroidproduction duringpregnancy, mostwomen willrequirea lowerexogenouscorticosteroiddoseand manywillnot needcorticosteroidtreatment duringpregnancy. NursingMothers:Itisnotknownwhetherfluticasone propionateisexcretedinhumanbreastmilk.Whentri tiatedfluticasone propionate wasadministered to ratsat a subcutaneous doseof 10mcg/kg(lessthanthe maximum recommended dailyintranasaldosein adultsona mcg/mbasis),radioactivity wasexcretedinthe milk.Becauseothercorticosteroids areexcretedinhumanmilk,cautionshouldbeexercisedwhenFLONASE NasalSprayisadministered toa nursingwoman. PediatricUse:Fivehundred(500)patientsaged4to 11yearsofage and440patientsaged12to17years werestudiedinUSclinicaltrialswithfluticasone propionate nasalspray.Thesafetyand effectiveness of FLONASE NasalSprayinchildrenbelow4 yearsofagehavenotbeenestablished. Oraland,to a lessclearextent,inhaledandintranasalcorticosteroidshavebeenshownto havethe potentialtocausea reduction ingrowthvelocityinchildrenandadolescents withextendeduse.Ifa childor adolescentonanycorticosteroid appearstohavegrowthsuppression, the possibility thattheyareparticularly sensitivetothiseffectofcorticosteroids shouldbeconsidered(seePRECAUTIONS). GeriatricUse:Alimitednumberofpatientsabove60yearsofage(n=275)havebeentreatedwithFLONASE NasalSprayinUSandnon-US clinicaltrals. Whilethenumberofpatientsistoosmalltopermitseparateanaly sisofefficacyandsafety,the adversereactionsreportedinthispopulation weresimilartothosereportedby youngerpatients. ADVERSE REACTIONS: IncontrolledUSstudies,morethan3300patientswithseasonalallergic,perennial allergic,orperennialnonallergic rhinitisreceivedtreatmentwithintranasalfluticasone propionate. Ingeneral, adversereactionsin clinicalstudieshavebeenprimarilyassociatedwithirritationof the nasalmucous membranes, andtheadversereactionswerereportedwithapproximately the samefrequencybypatients treatedwiththevehicleitself.Thecomplaintsdidnotusuallyinterferewithtreatment.Lessthan2%ofpatients in clinicaltrialsdiscontinued becauseofadverseevents;this ratewassimilarforvehicleplaceboandactive comparators. Systemic corticosteroid sideeffectswerenotreportedduringcontrolledclinicalstudiesupto6 months' durationwithFLONASE NasalSpray.Ifrecommended dosesareexceeded,however, orif individuals arepar ticularlysensitive,ortakingFLONASE NasalSprayin conjunction withadministration ofothercorticosteroids, symptoms ofhypercorticism, e.g.,Cushing'ssyndrome, couldoccur. Thefollowingincidence ofcommonadversereactions(>3%,whereincidenceinfluticasone propionate treatedsubjectsexceededplacebo)isbasedupon7controlled clinicaltrialsinwhich536patients(57girlsand 108boysaged4-11years,137femaleand234maleadolescents andadults)weretreatedwithFLONASE NasalSpray200mcgoncedailyover2 to4 weeksand2 controlledclinicaltrialsin which246patients (119femaleand127maleadolescents and adults)weretreatedwithFLONASE NasalSpray200mcgonce dailyover6months.Also includedinthetableareadverseeventsfrom2studiesinwhich167children (45girls and122boysaged4-11years)weretreatedwithFLONASE NasalSpray100mcgoncedailyfor2to4 weeks. OverallAdverseExperiences With>3%Incidence onFluticasone Propionate inControlled ClinicalTrialsWithFLONASE NasalSpray inPatients>4YearsWithSeasonalorPerennialAllergicRhinitis FLONASE FLONASE VehiclePlacebo 100mcgOnce 200mcgOnce AdverseExperience (n=758) (n=167) (n=782) Headache 14.6 6.6 16.1 Pharyngitis 7.2 6.0 7.8 Epistaxis 5.4 6.0 6.9 Nasalburning/ nasalirritation 2.6 2.4 3.2 Nausea/vomiting 2.0 4.8 2.6 Asthmasymptoms 2.9 7.2 3.3 Cough 2.8 3.6 3.8 Otheradverseeventsthat occurredin _3%but 1%of patientsandthatweremorecommonwith fluticasone propionate(withuncertainrelationshiptotreatment)included:bloodinnasalmucus,runnynose, abdominalpain,diarrhea,fever,flu-likesymptoms, achesandpains,dizziness,bronchitis. ObservedDuringClinicalPractice:Inadditiontoadverseeventsreportedfromclinicaltrials,thefollowing eventshavebeenidentifiedduringpostapproval useoffluticasonepropionatein clinicalpractice.Because theyare reportedvoluntarilyfroma population ofunknownsize,estimatesoffrequencycannotbe made. Theseeventshavebeenchosenforinclusion dueto eithertheirseriousness, frequency ofreporting,causal connection tofluticasonepropionate, occurrence duringclinicaltrials,ora combination ofthesefactors. General:Hypersensitivity reactions,including angioedema, skinrash,edemaofthe faceandtongue, pruritus,urticaria,bronchospasm, wheezing,dyspnea,and anaphylaxis/anaphylactoid reactions,whichin rareinstancesweresevere. Ear,Nose,and Throat:Alterationor loss ofsenseof tasteand/orsmelland, rarely,nasalseptal perforation, nasalulcer,sorethroat,throatirritationanddryness,cough,hoarseness,andvoicechanges. Eye: Drynessand irritation,conjunctivitis,blurredvision,glaucoma,increasedintraocular pressure,and cataracts. OVERDOSAGE: ChronicoverdosagewithFLONASENasalSpraymayresult in signs/symptoms of hypercorticism (seePRECAUTIONS). Intranasal administration of2 mg(10timesthe recommended dose)of fluticasonepropionatetwicedailyfor7 daysto healthyhumanvolunteerswas welltolerated.Single oraldosesupto 16 mghavebeenstudiedinhumanvolunteerswithno acutetoxiceffectsreported. Repeatoraldosesupto80mgdailyfor10 daysinvolunteersandrepeatoraldosesupto10mgdailyfor 14daysinpatientswerewelltolerated.Adversereactionswereofmildormoderateseverity,andincidences weresimilarin activeandplacebotreatmentgroups.Acuteoverdosagewiththis dosageformis unlikely since1 bottleofFLONASE NasalSpraycontainsapproximately 8 mgoffluticasone propionate. Theoralandsubcutaneous medianlethaldosesin miceandrats were>1000mg/kg(>20,000and >41,000times,respectively, themaximumrecommendeddailyintranasaldosein adultsand>10,000and >20,000times, respectively,the maximumrecommendeddaily intranasaldose in children ona mg/m'basis). GlaxoSmithKline GlaxoSmithKline Research Triangle Park, NC 27709 ©2001, GlaxoSmithKline All rights reserved. ©2002The GlaxoSmithKline Group of Companies Allrights reserved. Printed inUSA. 124ABS September 2001 RL-965 FL2297RO February2002
Links
Archive
2002 Mar
2002 May
Navigation
Previous Page
Next Page