FLORINEF

Main information

  • Trade name:
  • FLORINEF Tablets 0.1 Milligram
  • Dosage:
  • 0.1 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLORINEF Tablets 0.1 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0002/019/001
  • Authorization date:
  • 01-04-1978
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Florinef0.1mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsfludrocortisoneacetate0.1mg.

Alsocontainslactose,59.59mgpertablet

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Tablet.

Round,biconvex,whitetablets,scoredononesideandengravedontheothersidewith“SQUIBB”and“429”.

Thetabletscanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

ForpartialreplacementtherapyforprimaryadrenocorticalinsufficiencyinAddison’sdiseaseandforthetreatmentof

salt-losingadrenogenitalsyndrome.

4.2Posologyandmethodofadministration

Adults

Addison’sDisease

Adailydosagerangeof0.05to0.3mgFlorineftabletsorally.Supplementaryparenteraladministrationofsodium-

retaininghormonesisnotnecessary.Whenanenhancedglucocorticoideffectisnecessary,thisshouldbeachievedby

concurrentadministrationofcortisone(6.25to25mg)orhydrocortisone(5to20mg)daily.

Salt-losingAdrenogenitalSyndrome

Therecommendedoraldosagefortreatingsalt-losingadrenogenitalsyndromeisonetablet

(0.1mg)totwotablets(0.2mg)ofFlorinefdaily.Restrictionofsodiumintakeandsupplementarypotassium

administrationmayberequired.

Children

Dailydosageshouldbeadjustedtotheageandweightofthechildandtheseverityofthecondition.Cautionshouldbe

usedintheeventofexposuretochickenpox,measlesorothercommunicablediseases.(See4.4SpecialWarningsand

PrecautionsforUse).

Elderly

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4.3Contraindications

Useinpatientswithpepticulcer,activetuberculosis,acutepsychosis,acutebacterialorviralinfection.

Useinpatientshypersensitivetotheproductcomponents.

SinceFlorinefisapotentmineralocorticoidboththedosageandsaltintakeshouldbecarefullymonitoredtoavoidthe

developmentofhypertension,oedemaorweightgain.

Periodiccheckingofserumelectrolytelevelsisadvisableduringprolongedtherapy.

4.4Specialwarningsandprecautionsforuse

Adrenalcorticalatrophydevelopsduringprolongedtherapyandmaypersistforyearsafterstoppingtreatment.

Withdrawalofcorticosteroidsafterprolongedtherapymust,therefore,alwaysbegradualtoavoidacuteadrenal

insufficiencyandshouldbetaperedoffoverweeksormonthsaccordingtothedoseanddurationoftreatment.Patients

onlong-termsystemictherapywithFlorinefmayrequiresupportivecorticosteroidtherapyintimesofstress(suchas

trauma,surgeryorsevereillness)bothduringthetreatmentperiodanduptoayearafterwards.Ifcorticosteroidshave

beenstoppedfollowingprolongedtherapytheymayneedtobereintroducedtemporarily.

Patientsshouldcarrysteroidtreatmentcardswhichgiveclearguidanceontheprecautionstobetakentominimiserisk

andwhichprovidesdetailsofprescriber,drug,dosageandthedurationoftreatment.

Anti-inflammatory/immunosuppressiveeffects

Suppressionoftheinflammatoryresponseandimmunefunctionincreasesthesusceptibilitytoinfectionsandtheir

severity.Theclinicalpresentationmayoftenbeatypicalandseriousinfectionssuchassepticaemiaandtuberculosis

maybemaskedandmayreachanadvancedstagebeforebeingrecognised.

Chickenpox,shinglesandmeaslesareofparticularconcernsincethesenormallyminorillnessesmaybefatalin

immunosuppressedpatients.Patientsshouldbeadvisedtoavoidexposuretothesediseases,andtoseekmedicaladvice

withoutdelayifexposureoccurs.

Chickenpox

Unlesstheyhavehadchickenpox,patientsreceivingoralcorticosteroidsforpurposesotherthanreplacementshouldbe

regardedasbeingatriskofseverechickenpox.Manifestationsoffulminantillnessincludepneumonia,hepatitisand

disseminatedintravascularcoagulation:rashisnotnecessarilyaprominentfeature.Passiveimmunisationwith

varicellazosterimmunoglobulin(VZIG)isneededbyexposednon-immunepatientswhoarereceivingsystemic

corticosteroidsorwhohaveusedthemwithintheprevious3months;thisshouldpreferablybegivenwithin3daysof

exposure,andnotlaterthan10daysafterexposuretochickenpox.Confirmedchickenpoxwarrantsspecialistcareand

urgenttreatment.Corticosteroidsshouldnotbestoppedandthedosemayneedtobeincreased.

Measles

Prophylaxiswithnormalimmunoglobulinmaybeneeded.

Duringcorticosteroidtherapyantibodyresponsewillbereducedandthereforeaffectthepatient’sresponsetovaccines.

Livevaccinesshouldnotbeadministered.

Particularcareisrequiredwhenconsideringuseofsystemiccorticosteroidsinpatientswiththefollowingconditions

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Diverticulitis,recentintestinalanastomoses,thrombophlebitis,existingorprevioushistoryofsevereaffectivedisorders

(especiallyprevioussteroidpsychosis),exanthematousdisease,chronicnephritis,orrenalinsufficiency,metastatic

carcinoma,osteoporosis(post-menopausalfemalesareparticularlyatrisk);inpatientswithanactivepepticulcer(ora

historyofpepticulcer).

Myastheniagravis.Latentorhealedtuberculosis;inthepresenceoflocalorsystemicviralinfection,systemicfungal

infectionsorinactiveinfectionsnotcontrolledbyantibiotics.Inacutepsychoses;inacuteglomerulonephritis.

Hypertension;congestiveheartfailure;glaucoma(orafamilyhistoryofglaucoma),previoussteroidmyopathyor

epilepsy.

Allcorticosteroidsincreasecalciumexcretion.Corticosteroideffectsmaybeenhancedinpatientswithhypothyroidism

orcirrhosisanddecreasedinhyperthyroidpatients.

Diabetesmaybeaggravated,necessitatingahigherinsulindosage.Latentdiabetesmellitusmaybeprecipitated.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Menstrualirregularitiesmayoccur,andthispossibilityshouldbementionedtofemalepatients.

Patientsonlong-termsystemictherapywithFlorinefmayrequiresupportivecorticosteroidtherapyintimesofstress

(suchastrauma,surgeryorsevereillness),bothduringthetreatmentperiodandforayearafterwards.

Duringcorticosteroidtherapyantibodyresponsewillbereducedandthereforeaffectthepatient’sresponsetovaccines.

Rareinstancesofanaphylactoidreactionshaveoccurredinpatientsreceivingcorticosteroids,especiallywhenapatient

hasahistoryofdrugallergies.

Aspirinshouldbeusedcautiouslyinconjunctionwithcorticosteroidsinpatientswithhypoprothrombinaemia.

Therehavebeenafewreportsintheliteratureofthedevelopmentofcataractsinpatientswhohavebeenusing

corticosteroidsforprolongedperiodsoftime.Althoughitisnotpossibletoruleoutsystemiccorticosteroidsasaknown

factor,prescribersshouldbeawareofthepossibleroleofcorticosteroidsincataractdevelopment.

Patientsand/orcarersshouldbewarnedthatpotentiallyseverepsychiatricadversereactionsmayoccurwithsystemic

steroids(seesection4.8).Symptomstypicallyemergewithinafewdaysorweeksofstartingthetreatment.Risksmay

behigherwithhighdoses/systemicexposure(seealsosection4.5pharmacokineticinteractionsthatcanincreasethe

riskofsideeffects),althoughdoselevelsdonotallowpredictionoftheonset,type,severityordurationofreactions.

Mostreactionsrecoveraftereitherdosereductionorwithdrawal,althoughspecifictreatmentmaybenecessary.

Patients/carersshouldbeencouragedtoseekmedicaladviceifworryingpsychologicalsymptomsdevelop,especiallyif

depressedmoodorsuicidalideationissuspected.Patients/carersshouldalsobealerttopossiblepsychiatric

disturbancesthatmayoccureitherduringorimmediatelyafterdosetapering/withdrawalofsystemicsteroids,although

suchreactionshavebeenreportedinfrequently.

Particularcareisrequiredwhenconsideringtheuseofsystemiccorticosteroidsinpatientswithexistingorprevious

historyofsevereaffectivedisordersinthemselvesorintheirfirstdegreerelatives.Thesewouldincludedepressiveor

manic-depressiveillnessandprevioussteroidpsychosis.

Children

Growthanddevelopmentofchildrenonprolongedcorticosteroidtherapyshouldbecarefullyobserved.Prolongeduse

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Elderly

Thecommonadverseeffectsofsystemiccorticosteroidsmaybeassociatedwithmoreseriousconsequencesinoldage,

especiallyosteoporosis,hypertension,hypokalaemia,diabetes,susceptibilitytoinfectionandthinningoftheskin.

Closeclinicalsupervisionisrequiredtoavoidlife-threateningreactions.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

AmphotericinBinjectionandpotassium-depletingagents:Patientsshouldbeobservedforhypokalaemia.

Anti-cholinesterases:Effectsofanticholinesteraseagentsmaybeantagonised.

Anti-coagulants,oral:Corticosteroidsmaypotentiateordecreaseanticoagulantaction.Patientsreceivingoral

anticoagulantsandcorticosteroidsshouldthereforebecloselymonitored.

Anti-diabetics:Corticosteroidsmayincreasebloodglucose;diabeticcontrolshouldbemonitored,especiallywhen

corticosteroidsareinitiated,discontinued,orchangedindosage.

Anti-hypertensives,includingdiuretics:corticosteroidsantagonisetheeffectsofantihypertensivesanddiuretics.The

hypokalaemiceffectofdiuretics,includingacetazolamide,isenhanced.

Anti-tuberculardrugs:Isoniazidserumconcentrationsmaybedecreased.

Cyclosporin:Monitorforevidenceofincreasedtoxicityofcyclosporinwhenthetwoareusedconcurrently.

Digitalisglycosides:Co-administrationmayenhancethepossibilityofdigitalistoxicity.

Oestrogens,includeoralcontraceptives:Corticosteroidhalf-lifeandconcentrationmaybeincreasedandclearance

decreased.

HepaticEnzymeInducers(e.g.aminoglutethemide,barbiturates,carbamazepine,phenytoin,primidone,rifabutin,

rifampicin):TheremaybeincreasedmetabolicclearanceofFlorinef.Patientsshouldbecarefullyobservedforpossible

diminishedeffectofsteroid,andthedosageshouldbeadjustedaccordingly.

Humangrowthhormone:Thegrowth-promotingeffectmaybeinhibited.

Ketoconazole:Corticosteroidclearancemaybedecreased,resultinginincreasedeffects.

Non-depolarisingmusclerelaxants:Corticosteroidsmaydecreaseorenhancetheneuromuscularblockingaction.

Non-steroidalanti-inflammatoryagents(NSAIDs):corticosteroidsmayincreasetheincidenceand/orseverityofGI

bleedingandulcerationassociatedwithNSAIDs.Also,corticosteroidscanreduceserumsalicylatelevelsandtherefore,

decreasetheireffectiveness.Conversely,discontinuingcorticosteroidsduringhigh-dosesalicylatetherapymayresultin

salicylatetoxicity.Aspirinshouldbeusedcautiouslyinconjunctionwithcorticosteroidsinpatientswith

hypoprothrombinaemia.

Thyroiddrugs:Metabolicclearanceofadrenocorticoidsisdecreasedinhypothyroidpatientsandincreasedin

hyperthyroidpatients.Changesinthyroidstatusofthepatientmaynecessitateadjustmentinadrenocorticoiddosage.

Vaccines:Neurologicalcomplicationsandlackofantibodyresponsemayoccurwhenpatientstakingcorticosteriods

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4.6Fertility,pregnancyandlactation

Corticosteroidshavebeenshowntobeteratogenicinsomeanimalspecies;sofartherehasbeennoclearevidenceofa

similareffectinhumanbeings.

However,theyshouldnotbeusedinpregnancyunlessconsideredessentialbythephysician.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Corticosteroidadministrationwillresultincertaineffects,theseverity,significanceandextentofwhichvarywiththe

dosageanddurationoftreatmentandtheparticularcorticosteroidused.

Theseincludedisturbanceinelectrolytebalance,mineralmetabolism,glucosemetabolismandgluconeogenesis,

nitrogendepletion,diminishedlymphoidtissueandimmuneresponse,inhibitionofpituitaryfunction,Cushingoid

Syndrome,increaseinbloodcoagulability,diminishedinflammatoryresponse.Cataracts,psychosis,moodchanges,

avascularosteonecrosisandpancreatitismayoccur.Otherareasaffectedincludemusculoskeletal,gastrointestinal,

dermatologic,neurologicalandendocrine.

Awiderangeofpsychiatricreactionsincludingaffectivedisorders(suchasirritable,euphoric,depressedandlabile

mood,andsuicidalthoughts),psychoticreactions(includingmania,delusions,hallucinations,andaggravationof

schizophrenia),behavioraldisturbances,irritability,anxiety,sleepdisturbances,andcognitivedysfunctionincluding

confusionandamnesiahavebeenreported.Reactionsarecommonandmayoccurinbothadultsandchildren.Inadults,

thefrequencyofseverereactionshasbeenestimatedtobe5-6%.Psychologicaleffectshavebeenreportedon

withdrawalofcorticosteroids;thefrequencyisunknown.

4.9Overdose

Asinglelargedoseshouldbetreatedwithplentyofwaterbymouth.Carefulmonitoringofserumelectrolytesis

essential,withparticularconsiderationbeinggiventotheneedforadministrationofpotassiumchlorideandrestriction

ofdietarysodiumintake.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Notapplicable.

5.2Pharmacokineticproperties

Apotentmineralocorticoidwithsomeglucocorticoidproperties,wellabsorbed,metabolisedslowlywithaT½ofupto

30hours.Ithasstrongsodiumretainingcapacity.

5.3Preclinicalsafetydata

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Dibasiccalciumphosphate

Lactoseanhydrous

LactoseMonohydrate

Talc

MaizeStarch

MagnesiumStearate

SodiumBenzoate(E211)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years

6.4Specialprecautionsforstorage

Storeinarefrigerator(2-8°C).Keepthebottletightlyclosedtoprotectfrommoisture.

6.5Natureandcontentsofcontainer

TypeIIIAmberglassbottlesof100tabletswithacottonplug,inductionsealandpolypropylenecaps.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Bristol-MyersSquibbPharmaceuticalsLimited

Swords

CountyDublin

8MARKETINGAUTHORISATIONNUMBER

PA2/19/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:1stApril1978

Dateoflastrenewal:1stApril2008

10DATEOFREVISIONOFTHETEXT

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