CALCORT

Main information

  • Trade name:
  • CALCORT Tablets 1mg Milligram
  • Dosage:
  • 1mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CALCORT Tablets 1mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0535/005/001
  • Authorization date:
  • 15-06-1994
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0535/005/001

CaseNo:2035807

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ShirePharmaceuticalsLimited

HampshireInternationalBusiness,Chineham,Basingstoke,HampshireRG248EP,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CALCORT1mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom08/05/2007until14/06/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 15/05/2007 CRN 2035807 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Calcort1mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachtabletcontainsDeflazacort1mg.

Forexcipients,see6.1

3PHARMACEUTICALFORM

Tablet

Roundwhitetablet,plainononefaceandmarkedwitha‘1’ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Awiderangeofconditionsmaysometimesneedtreatmentwithglucocorticoids.Theindicationsinclude:

Primaryandsecondaryadrenocorticalinsufficiency,rheumatologicaldisorders,collagendiseases,pulmonarydiseases,

allergicconditions,haematologicaldiseases,neoplasticdiseases,dermatologicaldiseases,renaldiseases,

gastrointestinaldiseases,ophthalmicdiseasesandnervoussystemdisorders.

4.2Posologyandmethodofadministration

RouteofAdministration: Oral

RecommendedDosage:

Dosagemayrangeupto90mgdailyalthoughhigherdosescanbeadministered.Dosesshouldbeindividuallytitrated

accordingtodiagnosis,severityofdisease,prognosis,probabledurationofdiseaseortherapy,andpatientresponseand

tolerance.Thelowestdosethatwillproduceanacceptableresultshouldbeused;whenitispossibletoreducethe

dosage,thismustbeaccomplishedgradually.

Duringprolongedtherapy,dosagemayneedtobeincreasedtemporarilyduringperiodsofstressorinexacerbationof

illness.

ADULTS

AcuteDisorders-upto90mgdaily,dependingonseverityofsymptoms,forafewdays.

Dependingonclinicalresponse,doseshouldbegraduallydecreasedbyincrementstothelowesteffectivedose.

ChronicDisorders:

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HepaticImpairment:

Inpatientswithhepaticimpairment,bloodlevelsofdeflazacortmaybeincreased.Thereforethedoseofdeflazacort

shouldbecarefullymonitoredandadjustedtotheminimumeffectivedose.

RenalImpairment:

Inrenallyimpairedpatients,nospecialprecautionsotherthanthoseusuallyadoptedinpatientsreceivingglucocorticoid

therapyarenecessary.

Elderly:

Inelderlypatients,nospecialprecautionsotherthanthoseusuallyadoptedinpatientsreceivingglucocorticoidtherapy

arenecessary.Thecommonadverseeffectsofsystemiccorticosteroidsmaybeassociatedwithmoreserious

consequencesinoldage(seeWarningsandPrecautions).

Children:

Therehasbeenlimitedexposureofchildrentodeflazacortinclinicaltrials.

Inchildren,theindicationsforglucocorticoidsarethesameasforadults,butitisimportantthatthelowesteffective

dosageisused.Alternatedayadministrationmaybeappropriate(seeWarningsandPrecautions).Dosesofdeflazacort

usuallylieintherange0.25–1.5mg/kg/day.

4.3Contraindications

Systemicinfectionsunlessspecificanti-infectivetherapyisemployed.Hypersensitivitytodeflazacortoranyofthe

ingredients.Patientsreceivinglivevirusimmunisation.

4.4Specialwarningsandprecautionsforuse

Apatientinformationleafletshouldbesuppliedwiththisproduct.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheminimumperiod,andbyadministering

thedailyrequirementasasinglemorningdoseorwheneverpossibleasasinglemorningdoseonalternatedays.

Frequentpatientreviewisrequiredtoappropriatelytitratethedoseagainstdiseaseactivity(seeDosagesection).

Adrenalsuppression

Adrenalcorticalatrophydevelopsduringprolongedtherapyandmaypersistforyearsafterstoppingtreatment.

Withdrawalofcorticosteroidsafterprolongedtherapymustthereforealwaysbegradualtoavoidacuteadrenal

insufficiency,beingtaperedoffoverweeksormonthsaccordingtothedoseanddurationoftreatment.During

prolongedtherapy,anyintercurrentillness,traumaorsurgicalprocedurewillrequireatemporaryincreaseindosage;if

corticosteroidshavebeenstoppedfollowingprolongedtherapy,theymayneedtobetemporarilyre-introduced.

Patientsshouldcarry'Steroidtreatment'cardswhichgiveclearguidanceontheprecautionstobetakentominimiserisk

andwhichprovidedetailsofprescriber,drug,dosageandthedurationoftreatment.

Anti-inflammatory/immunosuppressiveeffectsandinfection

Suppressionoftheinflammatoryresponseandimmunefunctionincreasesthesusceptibilitytoinfectionsandtheir

severity.Theclinicalpresentationmayoftenbeatypicalandseriousinfectionssuchassepticaemiaandtuberculosis

maybemaskedandmayreachanadvancedstagebeforebeingrecognised.

Chickenpoxisofparticularconcernsincethisnormallyminorillnessmaybefatalinimmunosuppressedpatients.

Patients(orparentsofchildren)withoutadefinitehistoryofchickenpoxshouldbeadvisedtoavoidclosepersonal

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immunisationwithvaricellazosterimmunoglobulin(VZIG)isneededbyexposednon-immunepatientswhoare

receivingsystemiccorticosteroidsorwhohaveusedthemwithintheprevious3months;thisshouldbegivenwithin10

daysofexposuretochickenpox.Ifadiagnosisofchickenpoxisconfirmed,theillnesswarrantsspecialistcareand

urgenttreatment.Corticosteroidsshouldnotbestoppedandthedosemayneedtobeincreased.

Patientsshouldbeadvisedtotakeparticularcaretoavoidexposuretomeaslesandtoseekimmediatemedicaladviceifexposureoccurs.

Prophylaxiswithintramuscularnormalimmunoglobulinmaybeneeded.

Immunisationproceduresshouldnotbeundertakenwithpatientsonglucocorticoids,especiallyonhighdoses,because

ofthepossibilityofdisseminationoflivevaccinesand/orfailureofantibodyresponse.

Prolongeduseofglucocorticoidsmayproduceposteriorsubcapsularcataracts,glaucomawithpossibledamagetothe

opticnervesandmayenhancetheestablishmentofsecondaryocularinfectionsduetofungiorviruses.

Useinactivetuberculosisshouldberestrictedtothosecasesoffulminatinganddisseminatedtuberculosisinwhich

deflazacortisusedformanagementwithappropriateantituberculosisregimen.Ifglucocorticoidsareindicatedin

patientswithlatenttuberculosisortuberculinreactivity,closeobservationisnecessaryasreactivationofthedisease

mayoccur.Duringprolongedglucocorticoidtherapy,thesepatientsshouldreceivechemoprophylaxis.

Thefollowingclinicalconditionsrequirespecialcautionandfrequentpatientmonitoringisnecessary:

Cardiacdiseaseorcongestiveheartfailure,hypertension,thromboembolicdisorders.Glucocorticoidscancause

saltandwaterretention,andincreasedexcretionofpotassium.Dietarysaltrestrictionandpotassium

supplementationmaybenecessary.

Gastritisoroesophagitis,diverticulitis,ulcerativecolitisifthereisprobabilityofimpendingperforation,abscess

orpyogenicinfections,freshintestinalanastomosis,activeorlatentpepticulcer.

Diabetesmellitusorafamilyhistory,osteoporosis,myastheniagravis,renalinsufficiency.

Emotionalinstabilityorpsychotictendency,epilepsy.

Previouscorticosteroid-inducedmyopathy.

Liverfailure/cirrhosis.

Renalinsufficiency

Hypothyroidism

Ocularherpessimplexbecauseofpossiblecornealperforation.

UseinChildren:

Corticosteroidscausedose-relatedgrowthretardationininfancy,childhoodandadolescencewhichmaybeirreversible.

UseintheElderly:

Thecommonadverseeffectsofsystemiccorticosteroidsmaybeassociatedwithmoreseriousconsequencesinoldage,

especiallyosteoporosis,hypertension,hypokalaemia,diabetes,susceptibilitytoinfectionandthinningoftheskin.

Closeclinicalsupervisionisrequiredtoavoidlife-threateningreactions.

Sincecomplicationsofglucocorticoidtherapyaredependentondoseanddurationoftherapy,thelowestpossibledose

mustbegivenandarisk/benefitdecisionmustbemadeastowhetherintermittenttherapyshouldbeused.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Thesameprecautionsshouldbeexercisedasforotherglucocorticoids.Deflazacortismetabolisedintheliver.Itis

recommendedtoincreasethemaintenancedoseofdeflazacortifdrugswhichareliverenzymeinducersareco-

administered,e.g.rifampicin,rifabutin,carbamazepine,phenobarbitone,phenytoin,primidoneandaminoglutethimide.

Fordrugswhichinhibitliverenzymes,e.g.ketoconazoleitmaybepossibletoreducethemaintenancedoseof

deflazacort.

Inpatientstakingestrogens,corticosteroidrequirementsmaybereduced.

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corticosteroidsandthehypokalaemiceffectsofacetazolamide,loopdiuretics,thiazidediureticsandcarbenoxoloneare

enhanced.

Theefficacyofcoumarinanticoagulantsmaybeenhancedbyconcurrentcorticosteroidtherapyandclosemonitoringof

theINRorprothrombintimeisrequiredtoavoidspontaneousbleeding.

Inpatientstreatedwithsystemiccorticosteroids,useofnon-depolarisingmusclerelaxantscanresultinprolonged

relaxationandacutemyopathy.Riskfactorsforthisincludeprolongedandhighdosecorticosteroidtreatment,and

prolongeddurationofmuscleparalysis.Thisinteractionismorelikelyfollowingprolongedventilation(suchasinthe

ITUsetting).

Therenalclearanceofsalicylatesisincreasedbycorticosteroidsandsteroidwithdrawalmayresultinsalicylate

intoxication.

Asglucocorticoidscansuppressthenormalresponsesofthebodytoattackbymicroorganisms,itisimportanttoensure

thatanyanti-infectivetherapyiseffectiveanditisrecommendedtomonitorpatientsclosely.Concurrentuseof

glucocorticoidsandoralcontraceptivesshouldbecloselymonitoredasplasmalevelsofglucocorticoidsmaybe

increased.Thiseffectmaybeduetoachangeinmetabolismorbindingtoserumproteins.Antacidsmayreduce

bioavailability;leaveatleast2hoursbetweenadministrationofdeflazacortandantacids.

4.6Pregnancyandlactation

Humanreproductionstudieshavenotbeenperformedwithglucocorticoids,buttheyareknowntobeteratogenicin

animals.Deflazacortwasshowntohavedosedependentteratogeniceffectsinratsandrabbits.

Intra-uterinegrowthretardationinthefoetusandasmallincreasedriskofcleftpalatehavebeenreportedwith

corticosteroids.Hypoadrenalismmayoccurintheneonate.

Useduringpregnancyorduringlactationisnotrecommendedandshouldonlybeconsideredwhenpotentialbenefit

outweighspotentialrisk.Infantsborntomothersreceivingglucocorticoidsduringpregnancyshouldbecarefully

observedforsignsofhypoadrenalism.Glucocorticoidsareexcretedinmother’smilkandcancausegrowth

suppressionandhypoadrenalisminbreastfedinfants;thereforemotherstakingglucocorticoidsshouldbeadvisednotto

breastfeed.

4.7Effectsonabilitytodriveandusemachines

Onthebasisofthepharmacodynamicprofileandreportedadverseevents,itisunlikelythatdeflazacortwillproducean

effectontheabilitytodriveandusemachines.

4.8Undesirableeffects

Theincidenceofpredictableundesirableeffects,includinghypothalamic-pituitary-adrenalsuppressioncorrelateswith

therelativepotencyofthedrug,dosage,timingofadministrationandthedurationoftreatment(seeWarningsand

Precautions).

Endocrine/metabolic

Suppressionofthehypothalamic-pituitary-adrenalaxis,growthsuppressionininfancy,childhoodandadolescence,

menstrualirregularityandamenorrhoea.Cushingoidfacies,hirsutism,weightgain,impairedcarbohydratetolerance

withincreasedrequirementforanti-diabetictherapy,negativeproteinandcalciumbalance.Increasedappetite.

Anti-inflammatoryandimmunosuppressiveeffects

Increasedsusceptibilityandseverityofinfectionswithsuppressionofclinicalsymptomsandsigns,opportunistic

infections,recurrenceofdormanttuberculosis(seeWarningsandPrecautions).

Musculoskeletal

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(acutemyopathymaybeprecipitatedbynon-depolarisingmusclerelaxants–seesection4.5),negativenitrogen

balance.

Fluidandelectrolytedisturbance

Sodiumandwaterretentionwithhypertension,oedemaandheartfailure,potassiumloss,hypokalaemicalkalosis.

Neuropsychiatric

Headache,vertigo,euphoria,psychologicaldependence,hypomaniaordepression,insomnia,restlessnessand

aggravationofschizophrenia.Increasedintra-cranialpressurewithpapilloedemainchildren(pseudotumourcerebri),

usuallyaftertreatmentwithdrawal.Aggravationofepilepsy.

Ophthalmic

Increasedintra-ocularpressure,glaucoma,papilloedema,posteriorsubcapsularcataractsespeciallyinchildren,corneal

orscleralthinning,exacerbationofophthalmicviralorfungaldiseases.

Gastrointestinal

Dyspepsia,pepticulcerationwithperforationandhaemorrhage,acutepancreatitis(especiallyinchildren),candidiasis,

nausea.

Dermatological

Impairedhealing,skinatrophy,bruising,telangiectasia,striae,acne.

General

Hypersensitivityincludinganaphylaxishasbeenreported.Leucocytosis.Thromboembolism.Rareincidenceof

benignintracranialhypertension.

Withdrawalsymptomsandsigns

Toorapidareductionofcorticosteroiddosagefollowingprolongedtreatmentcanleadtoacuteadrenalinsufficiency,

hypotensionanddeath(seeWarningsandPrecautions).

A‘withdrawalsyndrome’mayalsooccurincludingfever,myalgia,arthralgia,rhinitis,conjunctivitis,painfulitchyskin

nodulesandlossofweight.Thismayoccurinpatientsevenwithoutevidenceofadrenalinsufficiency.

4.9Overdose

Itisunlikelythattreatmentisneededincasesofacuteoverdosage.TheLD

fortheoraldoseisgreaterthan

4000mg/kginlaboratoryanimals.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Deflazacortisaglucocorticoid.Itsanti-inflammatoryandimmunosuppressiveeffectsareusedintreatingavarietyof

diseasesandarecomparabletootheranti-inflammatorysteroids.Clinicalstudieshaveindicatedthattheaverage

potencyratioofdeflazacorttoprednisoneis0.64–0.89.

5.2Pharmacokineticproperties

Orallyadministereddeflazacortappearstobewellabsorbedandisimmediatelyconvertedbyplasmaesterasestothe

pharmacologicallyactivemetabolite(D21-OH)whichachievespeakplasmaconcentrationsin1.5to2hours.Itis

40%protein-boundandhasnoaffinityforcorticosteroid-binding-globulin(transcortin).Itseliminationplasmahalf-

lifeis1.1to1.9hours.Eliminationtakesplaceprimarilythroughthekidneys;70%oftheadministereddoseis

excretedintheurine.Theremaining30%iseliminatedinthefaeces.MetabolismofD21-OHisextensive;only18%

ofurinaryexcretionrepresentsD21-OH.ThemetaboliteofD21-OH,deflazacort6-beta-OH,representsone-thirdof

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5.3Preclinicalsafetydata

Safetystudieshavebeencarriedoutintherat,dog,mouseandmonkey.Thefindingsareconsistentwithother

glucocorticoidsatcomparabledoses.Teratogeniceffectsdemonstratedinrodentsandrabbitsaretypicalofthose

causedbyotherglucocorticoids.

Deflazacortwasnotfoundtobecarcinogenicinthemouse,butstudiesintheratproducedcarcinogenicfindings

consistentwiththefindingswithotherglucocorticoids.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

MicrocrystallineCellulose

LactoseMonohydrate

MaizeStarch

MagnesiumStearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.Donotstoreabove25 °

6.5Natureandcontentsofcontainer

Deflazacortwillbepackedinablisterpackofpolyvinylchlorideandaluminumfoilpresentedincardboardboxes.

Eachpackcontains100tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

None.

7MARKETINGAUTHORISATIONHOLDER

ShirePharmaceuticalsLimited,

HampshireInternationalBusinessPark,

Chineham,

Basingstoke,

Hampshire,RG248EP,

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:15 th

June1994

Dateoflastrenewal:15 th

June2004

10DATEOFREVISIONOFTHETEXT

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