DEXAMETHASONE

Main information

  • Trade name:
  • DEXAMETHASONE Tablets 2 Milligram
  • Dosage:
  • 2 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DEXAMETHASONE Tablets 2 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0061/010/002
  • Authorization date:
  • 12-01-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DexamethasoneTablets2mg.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains2mgofDexamethasone.

Excipients:Eachtabletcontainsapproximately116mglactosemonohydrate.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Tablet.

Round,6mm,flat,whitetabletwiththecode‘XC/8’engravedononesurfaceand‘Organon*’ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Dexamethasonetabletsareusedforthetreatmentofvariousinflammatoryandautoimmunediseasese.g.:

Rheumatism,aspain,stiffnessorlimitationofmotion,especiallyinthejointsandrelatedstructures,including

muscles,bursae,tendons,fibroustissue;

Collagendisease,aslupuserythematosus,dermatomyositis,polyarteritisnodosa,thromboticpurpuraandrheumatoid

arthritis;

Allergies,asstatusasthmaticus,bronchialasthma,contactdermatitis,inflammatoryprocessesoftheeyeandits

adnexa,severehypersensitivityreactionstodrugsorinsectstings,anaphylacticshock,impendingallograftrejection;

Primaryorsecondaryadrenocorticalinsufficiency,andadrenogenitalsyndromes.

BesidesDexamethasoneisusedasanadjunctinthecontrolofcerebraloedema(notinthosecaseswheretheoedema

iscausedbyheadinjury),fortreatmentoflymphocyticleukaemia,asanti-emeticinantineoplasticregimensandfor

palliativetreatmentinterminalstagesofneoplasticdisease.

4.2Posologyandmethodofadministration

Glucocorticoidsmaybeadministeredbyanumberofroutes,dependingonthenatureofthediseaseandthecondition

ofthepatient.Localisedtherapyisgenerallypreferredbecauseitminimisesadverseeffects.Whensystemic

administrationisrequired,theoralrouteispreferredforeaseinregulationofdoseandthevarietyinregimens.

Dexamethasonetabletsshouldbetakenorally,preferablywithsomefluid.

ThedosageofDexamethasonetabletsdependsontheseverityoftheconditionandtheresponseofthepatient.

Undesirableeffects,suchassuppressionofthehypothalamus-pituitary-adrenal(HPA)axismaybeminimisedbyusing

thelowesteffectivedosefortheminimumperiod,preferablybytakingthetablet(s)inthemorningandifdisease

controlwillallowalternatedaytherapy.Systemicdexamethasoneadministeredintheeveningismorelikelytocause

clinicallysignificantHPAsuppression.Alternatedaydosingisnotappropriateforpatientswithestablishedadrenal

insufficiency.Frequentpatientreviewisrequiredtoappropriatelytitratethedoseagainstdiseaseactivity.Ifno

favourableresponseisnotedwithinacoupleofdays,continuationofglucocorticoidtherapyisundesirable.

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continuousobservationoftheclinicalpicturetothelowestpossiblelevel,ortaperedoffcompletelybyfollowingthe

withdrawalschedulebelow.Dexamethasoneshouldonlybeadministeredtochildrenwithcaution,since

glucocorticoidscaninducegrowthretardation.Thedailydoseshouldbedeterminedbythephysicianforeachchild

individually.

Duringprolongedtherapyanyintercurrentillness,traumaorsurgicalprocedurewillrequireatemporaryincreasein

dosage.

Withdrawalofprolongedtherapy

Inpatientswhohavereceiveddexamethasoneformorethan3weeks,withdrawalshouldnotbeabrupt.Howdose

reductionshouldbecarriedout(taperedoffoverweeksormonths)dependslargelyonwhetherthediseaseislikelyto

relapseasthedoseofsystemicglucocorticoidsisreduced.Clinicalassessmentofdiseaseactivitymaythereforebe

neededduringwithdrawal.Ifthediseaseisunlikelytorelapseonwithdrawalbutthereisuncertaintyabout

hypothalamus-pituitary-adrenal(HPA)suppression,thedoseofsystemicdexamethasonemaybereducedrapidlyto

physiologicaldoses.Onceadailydoseofapprox.1mgdexamethasoneisreached,dosereductionshouldbeslowerto

allowtheHPA-axistorecover.

Abruptwithdrawalofsystemicdexamethasonetreatment,whichhascontinuedforupto3weeksisappropriateifitis

consideredthatthediseaseisunlikelytorelapse.Abruptwithdrawalofdosesuptoapprox.6mgdexamethasonefor3

weeksisunlikelytoleadtoclinicallyrelevantHPA-axissuppression,inthemajorityofpatients.

Inthefollowingpatientgroups,gradualwithdrawalofsystemicdexamethasonetherapyshouldbeconsideredeven

aftercourseslasting3weeksorless:

Patientswhohavehadrepeatedcoursesofsystemicdexamethasone(orothercorticosteroids),particularlyif

takenformorethan3weeks.

Whenashortcoursehasbeenprescribedwithinoneyearofcessationoflong-termtherapy(monthsoryears).

Patientswhomayhavereasonsforadrenocorticalinsufficiencyotherthanexogenousdexamethasone(orother

corticosteroid)therapy.

Patientsreceivingdosesofsystemicdexamethasonehigherthanapprox.6mg.

Patientsrepeatedlytakingdosesintheevening.

Patientswhoduringsystemictreatmentencounterstressessuchastrauma,surgeryorinfectionandwhoareatriskof

adrenalinsufficiencyshouldreceiveadditionalsystemicdexamethasonecoverduringtheseperiods.Thisincludes

patientswhohavefinishedacourseofsystemicdexamethasoneoflessthanthreeweeksdurationintheweekpriorto

thestress.Patientsonsystemicdexamethasonetherapywhoareatriskofadrenalsuppressionandareunabletotake

tabletsbymouthshouldreceiveparenteraldexamethasonecoverduringtheseperiods.

Toorapidreductionofdexamethasonedosagefollowingprolongedtreatmentcanleadtoacuteadrenalinsufficiency,

hypotensionanddeath.Characteristicsymptomsofa“withdrawalsyndrome”thatmayoccurarefever,myalgia,

arthralgia,rhinitis,conjunctivitis,painfulitchyskinnodulesandlossofweight.

4.3Contraindications

gastricandduodenalulcer;

acuteinfections:viralinfectionsandsystemicfungalinfections(bacterialinfections:seesection4.4.Special

warningsandprecautionsforuse);

hypersensitivitytoglucocorticoidsoroneoftheexcipients;

parasiticinfections;

vaccinationwithlivevaccines(seesection4.4.Specialwarningsandprecautionsforuse);

patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.4Specialwarningsandprecautionsforuse

Adrenalcorticalatrophydevelopsduringprolongedtherapyandmaypersistforyearsafterstoppingtreatment.

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insufficiency,beingtaperedoffoverweeksormonthsaccordingtothedoseanddurationoftreatment(see“withdrawal

ofprolongedtherapy”above).Duringprolongedtherapyanyintercurrentillness,traumaorsurgicalprocedurewill

requireatemporaryincreaseindosage;ifcorticosteroidshavebeenstoppedfollowingprolongedtherapytheymay

needtobetemporarilyre-introduced.

Anti-inflammatory/Immunosuppressiveeffects.Glucocorticoidtherapyisnon-specific,suppressesthesymptoms

andsignsofdiseaseanddecreasestheresistancetoinfections.Theclinicalpresentationmayoftenbeatypicaland

seriousinfectionssuchassepticaemiaandtuberculosismaybemaskedandmayreachanadvancedstagebeforebeing

recognised.Strongantimicrobialtherapyshouldaccompanyglucocorticoidtherapywhennecessary.

Vaccinesshouldnotbegiventoindividualswithglucocorticoidtherapy-inducedimmunosuppression.Vaccination

withlivevaccines,e.g.Chickenpoxisofparticularconcern.Chickenpoxisanormallyminorillnessbutmaybefatal

inimmunosuppressedpatients.Patients(orparentsofchildren)withoutadefinitehistoryofchickenpoxshouldbe

advisedtoavoidclosepersonalcontactwithchickenpoxorherpeszosterandifexposedtheyshouldseekurgent

medicalattention.Passiveimmunizationwithvaricella/zosterimmunoglobin(VZIG)isneededbyexposednon-

immunepatientswhoarerecivingsystemiccorticosteroidsorwhohaveusedthemwithintheprevious3months;this

shouldbegivenwithin10daysofexposuretochickenpox.Ifadiagnosisofchickenpoxisconfirmed,theillness

warrantsspecialistcareandurgenttreatment.Corticosteroidsshouldnotbestoppedandeventhedosemayneedtobe

increased.

Measlescanhaveamoreseriousorevenfatalcourseinimmunosuppressedpatients.Insuchchildrenoradults,

particularcareshouldbetakentoavoidexposuretomeasles.Ifexposed,prophylaxiswithintramuscularpooled

immunoglobulin(IVIG)maybeindicated.Exposedpatientsshouldbeadvisedtoseekmedicaladvicewithoutdelay.

Prolongeduseofcorticosteroidsmayproduceposteriorsubcapsularcataracts,glaucomawithpossibledamagetothe

opticnerveandmayenhancetheestablishmentofsecondaryocularinfectionsduetofungiorviruses.

Glucocorticoidscancausedose-relatedgrowthretardationininfancy,childhoodandadolescence,whichmaybe

irreversible.Therefore,Dexamethasoneshouldonlybeusedinchildrenwithcaution.

Thecommonadverseeffectsofsystemicglucocorticoidsmaybeassociatedwithmoreseriousconsequencesinold

age,especiallyosteoporosis,hypertension,hypokalaemia,diabetes,susceptibilitytoinfectionandthinningoftheskin.

Closeclinicalsupervisionisrequiredtoavoidlife-threateningreactions.

Particularcareisrequiredwhenconsideringtheuseofsystemicglucocorticoidsinpatientswiththefollowing

conditionsandfrequentpatientmonitoringisnecessary:

-Osteoporosis(post-menopausalwomenareparticularlyatrisk);

-Hypertensionorcongestiveheartfailure;

-Diabetesmellitus(orafamilyhistoryofdiabetes);

-Historyoftuberculosis;

-Glaucoma(orafamilyhistoryofglaucoma);

-Previousglucocorticoid-inducedmyopathy;

-Liverfailure;

-Renalinsufficiency;

-Epilepsy;

-Pepticulceration.

Patientsand/orcarersshouldbewarnedthatpotentiallyseverepsychiatricadversereactionsmayoccurwithsystemic

steroids(seesection4.8).Symptomstypicallyemergewithinafewdaysorweeksofstartingthetreatment.Risksmay

behigherwithhighdoses/systemicexposure(seealsosection4.5pharmacokineticinteractionthatcanincreasetherisk

ofsideeffects),althoughdoselevelsdonotallowpredictionoftheonset,type,severityordurationofreactions.Most

reactionsrecoveraftereitherdosereductionorwithdrawal,althoughspecifictreatmentmaybenecessary.

Patient/carersshouldbeencouragedtoseekmedicaladviceifworryingpsychologicalsymptomsdevelop,especiallyif

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disturbancesthatmayoccureitherduringorimmediatelyafterdosetapering/withdrawalofsystemicsteroids,although

suchreactionshavebeenreportedinfrequently.

Particularcareisrequiredwhenconsideringtheuseofsystemiccorticosteroidsinpatientswithexistingorprevious

historyofsevereaffectivedisordersinthemselvesorintheirfirstdegreerelatives.Thesewouldincludedepressiveor

manic-depressiveillnessandprevioussteroidpsychosis.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Rifampin,rifabutin,carbamazepine,phenobarbitone,phenytoin,primidoneandaminoglutethimideenhancethe

metabolismofglucocorticoidsandthetherapeuticeffectsmaybereduced.

Thedesiredeffectsofhypoglycaemicagents(includinginsulin),antihypertensivesanddiureticsareantagonisedby

glucocorticoids.

Theeffectsofanticholinesterasesareantagonisedbyglucocorticoidsinmyastheniagravis.

Concurrentuseofpotassium-depletingdiuretics(e.g.acetazolamide,loopdiuretics,thiazidediureticsor

carbenoxolone)andglucocorticoidsmayresultinseverehypokalaemia.

Theefficacyofcoumarinanticoagulantsmaybealteredbyconcurrentglucocorticoidtherapyandclosemonitoringof

theInternationalNormalisedRatioorprothrombintimeisrequired.

Therenalclearanceofsalicylatesisincreasedbyglucocorticoidsandsteroidwithdrawalmayresultinsalicylate

intoxication.

Combinationofcorticosteroidswithulcer-inducingagents(e.g.NSAID’s)enhancestheriskofpepticulceration.

4.6Fertility,pregnancyandlactation

Dexamethasonereadilycrossestheplacenta.

Thereareindicationsforaharmfuleffectofglucocorticoidsonthefoetusinanimalexperimentslikeabnormalitiesof

foetaldevelopmentincludingcleftpalateorlipandeffectsonbraingrowthanddevelopment.Therearenoadequate

datafromtheuseofdexamethasoneinpregnantwomentopredictanyeffectontheemryonicorfoetaldevelopment.

Whenadministeredforprolongedperiodsorrepeatedlyduringpregnancy,systemicglucocorticoidsincreasetheriskof

intra-uterinegrowthretardation(IUGR).ThereisnoevidenceforanincreasedincidenceofIUGRfollowingshort-term

treatment,suchasprophylactictreatmentforneonatalrespiratorydistresssyndrome.Inthiscase(topreventrespiratory

distresssyndrome),glucocorticoidsareessential.Patientswithpre-eclampsiaorfluidretentionrequireclose

monitoring.Dexamethasoneshould,formaternalindications,notbeusedduringpregnancyunlessclearlynecessary.

Adrenalsuppressionintheneonatefollowingprenatalglucocorticoidexposureistobeexpected.

Nodataareavailableonthetransferofdexamethasoneintobreastmilk.Becausecorticosteroidsareingeneralexcreted

intobreastmilk,andgiventhelackofexperience,breastfeedingisdiscouragedduringDexamethasonetherapy.

Aswithallmedicines,beforeprescribingsystemicglucocorticoidsinpregnancyorduringlactation,thebenefitsof

treatmentshouldbeweighedagainstthepotentialriskstobothmotherandchild.

4.7Effectsonabilitytodriveandusemachines

Glucocorticoidsmaycausemoodchanges(e.g.euphoriaordepression)orvisualdisturbances.Ifaffected,caution

shouldbeexercisedindrivingandoperatingmachinery.

4.8Undesirableeffects

Theincidenceofpredictableundesirableeffectsofglucocorticoidscorrelateswiththedosage,timingofadministration

anddurationoftreatment.Theclinicianmustbalancethetherapeuticeffectsofglucocorticoidswiththeirriskfor

adverseeffects,usingthelowestpossibleeffectivedosesfortheshortestpossibleperiodoftime,preferablybydosing

inthemorningonanalternatedaydosingregimen.Earlyrecognitionandappropriatemanagementofadverseeffects

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Awiderangeofpsychiatricreactionsincludingaffectivedisorders(suchasirritable,euphoric,depressedandlabile

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

schizophrenia),behaviouraldisturbances,irritability,anxiety,sleepdisturbances,andcognitivedysfunctionincluding

confusionandamnesiahavebeenreported.Reactionsarecommonandmayoccurinbothadultsandchildren.Inadults,

thefrequencyofseverereactionshasbeenestimatedtobe5-6%.Psychologicaleffectshavebeenreportedon

withdrawalofcorticosteroids;thefrequencyisunknown.

Table1:AdversereactionsofDexamethasone

*Thefrequencyofadversereactions:notknown(cannotbeestimatedfromtheavailabledata).

Systemorganclass PreferredTerm(s)orLowerLevelTerms

Frequencynotknown*

Bloodandlymphaticsystem

disorders Leucocytosis

Endocrinedisorders Hypothalamo-pituitarydisorder,Adrenal

suppression,Cushingoid,appearance

Eyedisorders Papilloedema(inchildrenwithpseudotumour

cerebri,usuallyafterwithdrawal),Glaucoma,

Cataractsubcapsular,Cornealthinning,Scleral

thinning

Gastrointestinaldisorders Gastriculcer(haemorrhage),Duodenalulcer

(haemorrhage),dyspepsia,pepticulcerperforation,

Pancreatitisacute

Generaldisordersand

administrationsiteconditions Oedema,Impairedhealing

Immunesystemdisorders Drughypersensitivity,Anaphylacticreaction

Infectionsandinfestations Infection(aggravated),opportunisticinfection,

tuberculosis(reactivated),Varicella,Eyeinfection

viralexacerbated,Eyeinfectionfungal

exacerbated,Candidiasis

Injury,poisoningandprocedural

complications (Spinal)fracture,Tendonrupture,Contusion

Investigations Weightincreased,Carbohydratetolerance

decreased,Intraocularpressureincreased,

Metabolismandnutritiondisorders Increasedappetite,Diabetesmellitusinadequate

control,Lipoproteindeficiency,Calcium

deficiency,Sodiumretention,Fluidretention,

Hypokalaemia,Alkalosishypokalaemic

Musculoskeletalandconnective

tissuedisorders Growthretardation(infancy,childhoodand

adolescence),Osteoporosis,Osteonecrosis,

Myopathy

Nervoussystemdisorders Intracranialpressureincreased(inchildrenwith

pseudotumourcerebri,usuallyafterwithdrawal),

Epilepsyaggravated

Psychiatricdisorders Nervousness,Euphoricmood,Drugdependence,

Depression,Insomnia,Schizophreniaaggravated,

Reproductivesystemandbreast

disorders Menstruationirregular,Amenorrhoea

Skinandsubcutaneoustissue

disorders Dermatitisallergic,Hirsutism,Skinatrophy,

Telangiectasia,Skinstriae,Acne

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Inanimalexperiments,theacutetoxicityofdexamethasonehasbeenshowntoberatherlow.Symptomsofacute

overdosagethatcanoccurarenauseaandvomiting.Ifvomitinghasnotyetoccurredthiscanbeprovoked.Fortherest

asymptomatictreatmentisprobablysufficient.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Dexamethasonetabletscontainsasactiveingredientdexamethasone,whichisasyntheticglucocorticoidwith

approximatelya7timeshigheranti-inflammatorypotencythanprednisoloneand30timesthatofhydrocortisone.

Glucocorticoidsareproducedandsecretedbytheadrenalcortexandareanintrinsicpartofthehypothalamus-pituitary-

adrenalaxis(HPA-axis).Inphysiologicalconcentrationsglucocorticoids,bothnaturallyoccurring(hydrocortisoneor

cortisone)orsynthetic(likedexamethasone)exertabroadrangeofeffectsonmultipleorgansystemsandtissues;they

affectcarbohydrate,protein,lipidandcalciummetabolismandhaveeffectsonfluidandelectrolytebalanceandare

importantforsupportofnormalcardiovascularstructureandfunctionandthenormalfunctionofskeletalmuscle.

Intargettissuesglucocorticoidsinteractwithspecificreceptorproteinstoregulate,viatheexpressionofglucocorticoid-

responsivegenes,proteinsynthesis.Asaconsequenceofthetimerequiredforchangesingeneexpressionandprotein

synthesis,mosteffectsofglucocorticoidsarenotimmediate,butbecomeapparentafterseveralhours.Thisfactisof

clinicalsignificance,becauseadelaygenerallyisseenbeforebeneficialeffectsofglucocorticoidtherapyareobserved.

Dexamethasoneistherapeuticallyusedmostlybecauseofitsanti-inflammatoryandimmunosuppressiveproperties.

Dexamethasonehasvirtuallynomineralocorticoidactivitywhichmakesitsuitableforuseinpatientswithcardiac

failureorhypertension.

5.2Pharmacokineticproperties

Afteringestion,dexamethasoneisrapidlyandwell(around80%)absorbed.Peakplasmalevelsarereachedbetween1

and2hoursafteringestion.

Dexamethasoneisbound(upto77%)byplasmaproteins,mainlyalbumin.Thereishighuptakeofdexamethasoneby

theliver,kidneyandadrenalglands.Metabolismintheliverisslowandexcretionismainlyintheurine,largelyas

unconjugatedsteroids.Theplasmahalf-lifeis3.0-4.5hoursbut,astheeffectssignificantlyoutlastplasma

concentrationsofsteroids,theplasmahalf-lifeisoflittlerelevanceandtheuseofthebiologicalhalf-lifeismore

applicable.Thebiologicalhalf-lifeofdexamethasoneis36-54hours.ThereforeDexamethasoneisespeciallysuitablein

conditionswherecontinuousglucocorticoidactionisdesirable.

5.3Preclinicalsafetydata

Inanimalstudies,cleftpalatewasobserved.Thiswasseeninrats,mice,hamsters,rabbits,dogsandprimates.Insome

casesthiswascombinedwithdefectstothecentralnervoussystemandtheheart.Inprimates,effectstothebrainwere

seen.Moreover,intra-uterinegrowthcanbedelayed.Alltheseeffectswereseenathighdosages.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Propyleneglycol

Potatostarch

Magnesiumstearate

Lactosemonohydrate

6.2Incompatibilities

Noneknown

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3years.

6.4Specialprecautionsforstorage

Storebelow25°C.Storeintheoriginalpackage(toprotectfromlight).

6.5Natureandcontentsofcontainer

Polyethylene‘tampercontainer’tabletcontainerswithchildresistantclosures,containing100or500tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

OrganonIreland

DrynamRoad

Swords

Co.Dublin

8MARKETINGAUTHORISATIONNUMBER

PA61/10/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01April1978

Dateoflastrenewal:29November2007

10DATEOFREVISIONOFTHETEXT

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