CALMAX

Main information

  • Trade name:
  • CALMAX Tablets 0.25mg Milligram
  • Dosage:
  • 0.25mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CALMAX Tablets 0.25mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0915/025/001
  • Authorization date:
  • 28-05-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Calmax0.25mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains0.25mgofAlprazolam.

Excipients:Eachtabletcontains97.32mgofLactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets.

White,oblongtabletsembossedwith“apzm0.25”andabreakline.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Anxiety

Benzodiazepinesareonlyindicatedwhenthedisorderissevere,disablingorsubjectingtheindividualtoextreme

distress.

4.2Posologyandmethodofadministration

Anxiety

Treatmentshouldbeasshortaspossible.Theoveralldurationoftreatmentgenerallyshouldnotbemorethan8-12

weeks,includingataperingoffprocess.Thepatientshouldbereassessedregularlyandtheneedforcontinued

treatmentshouldbeevaluated,especiallyincasethepatientissymptomfree.

Itisusualtocommencewithadoseof500mcgto1mgdailyindivideddoses,withincrements(nogreaterthan1mg

every3-4days),tothelevelofoptimalcontrolusually3to4mgdaily.

Intheelderlyordebilitatedpatientaregimenof250mcgtwicedailyshouldbeusedinitiallywithgradualincrementsif

requiredandtoleranceisassured.

Treatmentshouldbestartedwiththelowerrecommendeddose.Themaximumdoseshouldnotbeexceeded.

Initialdosesmaybegivenatbedtimetominimisedaytimelethargy.Ifsideeffectsoccurwiththestartingdose,the

doseshouldbelowered.

Incertaincasesextensionbeyondthemaximumtreatmentperiodmaybenecessary;ifso,itshouldnottakeplace

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4.3Contraindications

Myastheniagravis

Hypersensitivitytobenzodiazepines

Severerespiratoryinsufficiency

Sleepapnoeasyndrome

Severehepaticinsufficiency

4.4Specialwarningsandprecautionsforuse

Tolerance

Somelossofefficacytothehypnoticeffectsofbenzodiazepinesmaydevelopafterrepeateduseforafewweeks.

Dependence

Useofbenzodiazepinesmayleadtothedevelopmentofphysicalandpsychicdependenceupontheseproducts.The

riskofdependenceincreaseswithdoseanddurationoftreatment;itisalsogreaterinpatientswithahistoryofalcohol

ordrugabuse.

Oncephysicaldependencehasdeveloped,abruptterminationoftreatmentwillbeaccompaniedbywithdrawal

symptoms.Thesemayconsistofheadaches,musclepain,extremeanxiety,tension,restlessness,confusionand

irritability.Inseverecasesthefollowingsymptomsmayoccur:derealization,depersonalization,hyperacusis,

numbnessandtinglingoftheextremities,hypersensitivitytolight,noiseandphysicalcontact,hallucinationsor

epilepticseizures.

Reboundinsomniaandanxiety:atransientsyndromewherebythesymptomsthatledtotreatmentwitha

benzodiazepinerecurinanenhancedformmayoccuronwithdrawaloftreatment.Itmaybeaccompaniedbyother

reactionsincludingmoodchanges,anxietyorsleepdisturbancesandrestlessness.Sincetheriskofwithdrawal

phenomena/reboundphenomenaisgreaterafterabruptdiscontinuationoftreatment,itisrecommendedthatthedosage

isdecreasedgradually.

Durationoftreatment

Thedurationoftreatmentshouldbeasshortaspossible(seePosology)butshouldnotexceedeighttotwelveweeks

includingtaperingoffprocess.Extensionbeyondtheseperiodsshouldnottakeplacewithoutre-evaluationofthe

situation.

Itmaybeusefultoinformthepatientwhentreatmentisstartedthatitwillbeoflimiteddurationandtoexplain

preciselyhowthedosagewillbeprogressivelydecreased.

Moreoveritisimportantthatthepatientshouldbeawareofthepossibilityofreboundphenomena,therebyminimising

anxietyoversuchsymptomsshouldtheyoccurwhilethemedicinalproductisbeingdiscontinued.

Thereareindicationsthat,inthecaseofbenzodiazepineswithashortdurationofaction,withdrawalphenomenacan

becomemanifestwithinthedosageinterval,especiallywhenthedosageishigh.Whenbenzodiazepineswithalong

durationofactionarebeinguseditisimportanttowarnagainstchangingtoabenzodiazepinewithashortdurationof

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Amnesia

Benzodiazepinesmayinduceanterogradeamnesia.Theconditionoccursmostoftenseveralhoursafteringestingthe

productandthereforetoreducetheriskpatientsshouldensurethattheywillbeabletohaveanuninterruptedsleepof

7-8hours(seealsoUndesirableEffects).

Psychiatricand'paradoxical'reactions

Reactionslikerestlessness,agitation,irritability,aggressiveness,delusion,rages,nightmares,hallucinations,psychoses,

inappropriatebehaviourandotheradversebehaviouraleffectsareknowntooccurwhenusingbenzodiazepines.Should

thisoccur,useofthedrugshouldbediscontinued.

Theyaremorelikelytooccurinchildrenandtheelderly.

Specificpatientgroups

Benzodiazepinesshouldnotbegiventochildrenwithoutcarefulassessmentoftheneedtodoso;thedurationof

treatmentmustbekepttoaminimum.Elderlyshouldbegivenareduceddose(seePosology).Alowerdoseisalso

recommendedforpatientswithchronicrespiratoryinsufficiencyduetotheriskofrespiratorydepression.

Benzodiazepinesarenotindicatedtotreatpatientswithseverehepaticinsufficiencyastheymayprecipitate

encephalopathy.

Benzodiazepinesarenotrecommendedfortheprimarytreatmentofpsychoticillness.

Benzodiazepinesshouldnotbeusedalonetotreatdepressionoranxietyassociatedwithdepression(suicidemaybe

precipitatedinsuchpatients).

Benzodiazepinesshouldbeusedwithextremecautioninpatientswithahistoryofalcoholordrugabuse.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Notrecommended Concomitantintakewithalcohol

Thesedativeeffectmaybeenhancedwhentheproductisusedincombinationwithalcohol.Thisaffectstheability

todriveorusemachines.

Takeintoaccount CombinationwithCNSdepressants

Enhancementofthecentraldepressiveeffectmayoccurincasesofconcomitantusewithantipsychotics

(neuroleptics),hypnotics,anxiolytics/sedatives,antidepressantagents,narcoticanalgesics,anti-epilepticdrugs,

anaestheticsandsedativeantihistamines.

Inthecaseofnarcoticanalgesicsenhancementoftheeuphoriamayalsooccurleadingtoanincreaseinpsychic

dependence.

Compoundswhichinhibitcertainhepaticenzymes(particularlycytochromeP450)mayenhancetheactivityof

benzodiazepines.Toalesserdegreethisalsoappliestobenzodiazepinesthataremetabolisedonlybyconjugation.

4.6Pregnancyandlactation

Benzodiazepinesshouldonlybeusedduringpregnancyorlactationifconsideredessentialbythephysician.Animal

studieswithbenzodiazepineshaveshownminoreffectsonthefoetuswhileafewstudieshavereportedlatebehavioural

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Iftheproductisprescribedtoawomanofchildbearingpotential,sheshouldbewarnedtocontactherphysician

regardingdiscontinuanceoftheproductifsheintendstobecomeorsuspectsthatsheispregnant.

If,forcompellingmedicalreasons,theproductisadministeredduringthelatephaseofpregnancy,orduringlabour,

effectsontheneonate,suchashypothermia,hypotoniaandmoderaterespiratorydepression,canbeexpected,dueto

thepharmacologicalactionofthecompound.Moreover,infantsborntomotherswhotookbenzodiazepineschronically

duringthelatterstagesofpregnancymayhavedevelopedphysicaldependenceandmaybeatsomeriskfordeveloping

withdrawalsymptomsinthepostnatalperiod.

Sincebenzodiazepinesarefoundinthebreastmilk,benzodiazepinesshouldnotbegiventobreastfeedingmothers.

4.7Effectsonabilitytodriveandusemachines

Sedation,amnesia,impairedconcentrationandimpairedmuscularfunctionmayadverselyaffecttheabilitytodriveor

tousemachines.Ifinsufficientsleepdurationoccurs,thelikelihoodofimpairedalertnessmaybeincreased(seealso

Interactions).

4.8Undesirableeffects

Drowsiness(whentheproductisusedasahypnoticitshouldbestatedexplicitly:drowsinessduringtheday),numbed

emotions,reducedalertness,confusion,fatigue,headache,dizziness,muscleweakness,ataxiaordoublevision.These

phenomenaoccurpredominantlyatthestartoftherapyandusuallydisappearwithrepeatedadministration.

Othersideeffectslikegastrointestinaldisturbances,changesinlibidoorskinreactionshavebeenreported

occasionally.

Amnesia

Anterogradeamnesiamayoccurusingtherapeuticdosages,theriskincreasingathigherdosages.Amnesiceffectsmay

beassociatedwithinappropriatebehaviour.(SeeWarningsandPrecautions).

Depression

Pre-existingdepressionmaybeunmaskedduringbenzodiazepineuse.

Psychiatricand'paradoxical'reactions

Reactionslikerestlessness,agitation,irritability,aggressiveness,delusion,rages,nightmares,hallucinations,psychoses,

inappropriatebehaviourandotheradversebehaviouraleffectsareknowntooccurwhenusingbenzodiazepineor

benzodiazepine-likeagents.Theymaybequiteseverewiththisproduct.Theyaremorelikelytooccurinchildrenand

theelderly.

Dependence

Use(evenattherapeuticdoses)mayleadtothedevelopmentofphysicaldependence:discontinuationofthetherapy

mayresultinwithdrawalorreboundphenomena(seeWarningsandPrecautions).Psychicdependencemayoccur.

Abuseofbenzodiazepineshasbeenreported.

4.9Overdose

Aswithotherbenzodiazepines,overdoseshouldnotpresentathreattolifeunlesscombinedwithotherCNS

depressants(includingalcohol).

Inthemanagementofoverdosewithanymedicinalproduct,itshouldbeborneinmindthatmultipleagentsmayhave

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Followingoverdosewithanymedicinalproduct,vomitingshouldbeinduced(withinonehour)ifthepatientis

consciousorgastriclavageundertakenwiththeairwayprotectedifthepatientisunconscious.Ifthereisnoadvantage

inemptyingthestomach,activatedcharcoalshouldbegiventoreduceabsorption.

Specialattentionshouldbepaidtorespiratoryandcardiovascularfunctionsinintensivecare.

Overdoseofbenzodiazepinesisusuallymanifestedbydegreesofcentralnervoussystemdepressionrangingfrom

drowsinesstocoma.

Inmildcases,symptomsincludedrowsiness,mentalconfusionandlethargy,inmoreseriouscases,symptomsmay

includeataxia,hypotonia,hypotension,respiratorydepression,rarelycomaandveryrarelydeath.

Flumazenilmaybeusefulasanantidote.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Alprazolam,likeotherbenzodiazepines,hasahighaffinityforthebenzodiazepinebindingsiteinthebrain.It

facilitatestheinhibitoryneurotransmitteractionofgamma-aminobutyricacidwhichmediatesbothpre-andpost-

synapticinhibitioninthecentralnervoussystem(CNS).

5.2Pharmacokineticproperties

Followingoraladministration,peakplasmaconcentrationsarereachedinabout1.7hours.Afterasingleoraldoseof

500mcg,theaveragemaximalconcentrationwas7.1ng/ml.Thereisalinearrelationshipbetweenthedoseandplasma

concentration.Atleast80%oftheoraldoseisabsorbed.About70%oftheabsorbeddoseisboundtoplasma

proteins.Alprazolamisextensivelymetabolisedintheliver,primarilytohydroxylatedmetabolites,butabout20%of

thedoseisexcretedasunchangedalprazolam.Eliminationoccursmostlyviathekidneys;80%ofthedoseisexcreted

intotheurineandonly7%intothefaeces.Themeaneliminationhalf-lifeis10-12hours.

5.3Preclinicalsafetydata

None.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

DocusateSodium

SodiumBenzoate(E211)

PregelatinisedStarch

MicrocrystallineCellulose

LactoseMonohydrate

ColloidalAnhydrousSilica

MagnesiumStearate

6.2Incompatibilities

Notapplicable

6.3ShelfLife

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6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Keepthetabletsintheblisterintheoutercartontoprotectfromlightandmoisture.

6.5Natureandcontentsofcontainer

Blisterpacksconsistingof250µmclearPVCand20µmhardtemperaluminiumfoilcontainedinacarton.

Packsizes:30,50,60and100tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

HelsinnBirexTherapeuticsLtd

Damastown

Mulhuddart

Dublin15

8MARKETINGAUTHORISATIONNUMBER

PA915/25/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 4March1999

Dateoflastrenewal: 4March2009

10DATEOFREVISIONOFTHETEXT

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