BELLVIRAX

Main information

  • Trade name:
  • BELLVIRAX Tablets 200 mg Milligram
  • Dosage:
  • 200 mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BELLVIRAX Tablets 200 mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/053/001
  • Authorization date:
  • 27-05-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Bellvirax200mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each200mgtabletcontains200mgaciclovir.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets.

Capsuleshaped,biconvex,uncoatedwhitetooff-whitetabletswith‘200’embossedononesideand‘ACV’onthe

otherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

BellviraxTabletsareindicatedforthefollowing:

treatmentofherpessimplexvirusinfectionsinvolvingtheskinandmucousmembranes,includinginitialand

recurrentgenitalherpes,

suppressionofrecurrenceofherpessimplexvirusinfectionsinimmunocompetentpatients,

prophylaxisagainstherpessimplexvirusinfectionsinimmunocompromisedindividuals,

treatmentofherpeszoster(shingles)andvaricella(chickenpox)infections.

4.2Posologyandmethodofadministration

BellviraxTabletsshouldbedissolvedin100ml(aglassful)ofwaterimmediatelybeforetaking,orswallowed

wholewithwater,accordingtothefollowingdosageschedules:

Adults:

Treatmentofherpessimplexvirusinfections:

200mg,fivetimesadayatfour-hourlyintervals,omittingthenighttimedose.Treatmentisusuallyfor5days,but

canbeextended,dependingontheseverityoftheinfection.

Inpatientswhoareseverelyimmunocompromisedorwithmalabsorption,thedosemaybeincreasedto400mg.

Treatmentshouldbestartedassoonasinfectionisevident;i.e.whenlesionsfirstappear,orforrecurrentinfections,

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Suppressionofrecurrentherpessimplexinfectionsinimmunocompetentpatients:

200mg,fourtimesadayatsix-hourlyintervalsor400mgtwicedailyattwelve-hourlyintervals.

Thisdosemaybereducedaccordingtoprogress,to200mg,threetimesdailyateight-hourlyintervalsortwice

dailyattwelve-hourlyintervals;howeveritshouldberememberedthattotaldailydosesof800mgorlessmaybe

associatedwithbreakthroughviralinfection.

Treatmentshouldbestoppedtemporarilyafterperiodsofsixtotwelvemonthstoassessthestatusofthepatient’s

disease.

Prophylaxisofherpessimplexvirusinfectionsinimmunocompromisedindividuals:

200mg,takenfourtimesdailyatsix-hourlyintervals.Inpatientswithsevereimpairmentoftheimmunesystem,for

exampleafterabonemarrowtransplant,orinpatientswithimpairedgastrointestinalabsorption,thedosecanbe

increasedto400mg.Intravenousdosingmaybeconsideredasanalternative.

Thelengthoftreatmentisdeterminedbythelengthoftimeduringwhichthepatientisjudgedtobeatriskof

infection.

Treatmentofherpeszosterandvaricellainfections:

800mg,fivetimesdailyatfour-hourlyintervalsfor7days,omittingthenighttimedose.

Intravenousdosingmaybeconsideredinseverelyimmunocompromisedpatientsorinthosewithimpaired

gastrointestinalabsorption.

Inbothdiseases,treatmentshouldbestartedassoonaspossibleaftertheonsetofarashorothersymptomsare

recognised.

Children:

Treatmentofherpessimplexvirusinfectionsandprophylaxisintheimmunocompromised:

Theadultdosagesmaybeusedinchildrentwoyearsandolder.

Childrenbelowtwoshouldreceivehalftheadultdose.

Treatmentofvaricellainfections:

Childrensixyearsandolder:800mg,fourtimesaday.

Twotofiveyears:400mg,fourtimesaday.

Undertwoyears:200mg,fourtimesaday.

Thesedosagesshouldbecontinuedfor5days.

Ifrequired,dosesmaybecalculatedona20mg/kgbodyweightbasis,fourtimesdaily.Asingledoseshouldnot

exceed800mg.

Theelderly:

Dosageshouldbedeterminedwithreferencetokidneyfunction,asindicatedbycreatinineclearance.Dosesshouldbe

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Effortsshouldbemadetoensureadequatehydrationofelderlypatientstakinghighoraldosesofaciclovir.

Dosageinrenalimpairment:

Treatmentofherpessimplexvirusinfections:

Severerenalimpairment(creatinineclearance<10ml/minute):amaximumdoseof200mg,twicedaily,attwelve-

hourlyintervalsisrecommended.

Treatmentofherpeszosterandvaricellainfections:

Severerenalimpairment(creatinineclearance<10ml/minute):amaximumdoseof800mg,twicedailyattwelve-

hourlyintervals.

Moderaterenalimpairment(creatinineclearancebetween10and25ml/minute):800mg,threetimesadayatsixto

eighthourlyintervals.

4.3Contraindications

HypersensitivitytoAciclovirorvalacicloviroranycomponentofaciclovirtablets.

4.4Specialwarningsandprecautionsforuse

Hydrationstatus:Careshouldbetakentomaintainadequatehydrationinpatientsreceivinghighoraldosesofaciclovir.

Totalbodyclearanceofaciclovirdeclinesalongwithcreatinineclearanceandspecialattentionshouldbegivento

dosagereductioninelderlyandotherpatientswithimpairedcreatinineclearance.

Aciclovirhasnotbeenshowntoreducetheincidenceofcomplicationsassociatedwithchickenpoxin

immunocompromisedpatients.

Inseverelyimmunocompromisedpatients,prolongedorrepeatedcoursesofaciclovirmayresultintheselectionof

viralstrainswithreducedsensitivitytothedrug;thesemaynotrespondtocontinueduse.

Evidencefromawiderangeofinvitroandinvivostandard,mutagenicitytestsindicatethataciclovirisunlikelyto

producegeneticabnormalitiesinman.Longitudinalstudiesinmiceandratsindicatednocarcinogenicpotential.

Reversibleeffectsonspermatogenesishavebeenobservedinratsanddogs,atmuchhigherdosesofaciclovirthan

thoserecommendedfortherapeuticpurposesinman.Aciclovirhasnotbeenshowntoproducedefinitiveeffectson

spermcount,morphologyormotilityinman.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noclinicallysignificantinteractionshavebeenidentified.

Acicloviriseliminatedprimarilyunchangedintheurineviaactiverenaltubularsecretion.Anydrugsadministered

concurrentlythatcompetewiththismechanismmayincreaseaciclovirplasmaconcentrations.Probenecidand

cimetidineincreasetheAUCofaciclovirbythismechanism,andreduceaciclovirrenalclearance.Similarlyincreases

inplasmaAUCsofaciclovirandoftheinactivemetaboliteofmycophenolatemofetil,animmunosuppressantagent

usedintransplantpatientshavebeenshownwhenthedrugsareco-administered.Howevernodosageadjustmentis

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4.6Fertility,pregnancyandlactation

Pregnancy:Apost-marketingaciclovirpregnancyregistryhasdocumentedpregnancyoutcomesinwomenexposedto

anyformulationofaciclovir.Theregistryfindingshavenotshownanincreaseinthenumberofbirthdefectsamongst

aciclovirexposedsubjectscomparedwiththegeneralpopulation,andanybirthdefectsshowednouniquenessor

consistentpatterntosuggestacommoncause.

Cautionshouldhoweverbeexercisedbybalancingthepotentialbenefitsoftreatmentagainstanypossiblehazard.

Teratogenicity:Systemicadministrationofaciclovirininternationallyacceptedstandardtestsdidnotproduce

embryotoxicorteratogeniceffectsinrabbits,ratsormice.Inannon-standardtestinrats,foetalabnormalitieswere

observedbutonlyfollowingsuchhighsubcutaneousdosesthatmaternaltoxicitywasproduced.Theclinicalrelevance

ofthesefindingsisuncertain.

Lactation:Followingoraladministrationof200mgaciclovirfivetimesaday,aciclovirhasbeendetectedinbreast

milkatconcentrationsrangingfrom0.6to4.1timesthecorrespondingplasmalevels.Theselevelswouldpotentially

exposenursinginfantstoaciclovirdosagesofupto0.3g/kg/day.CautionisthereforeadvisedifBellviraxistobe

administeredtoanursingwoman.

4.7Effectsonabilitytodriveandusemachines

TheclinicalstatusofthepatientandtheadverseeventprofileofBellviraxshouldbeborneinmindwhenconsidering

thepatient’sabilitytodriveoroperatemachinery.TherehavebeennostudiestoinvestigatetheeffectofBellviraxon

drivingperformanceortheabilitytooperatemachinery.Further,adetrimentaleffectonsuchactivitiescannotbe

predictedfromthepharmacologyoftheactivesubstance.

4.8Undesirableeffects

Thefrequencycategoriesassociatedwiththeadverseeventsbelowareestimates.Formostevents,suitabledatafor

estimatingincidencewerenotavailable.Inaddition,adverseeventsmayvaryintheirincidencedependingonthe

addiction.

Thefollowingconventionhasbeenusedfortheclassificationofundesirableeffectsintermsoffrequency:Very

common 1/10,common 1/100and<1/10,uncommon1/1000and<1/100,rare1/10,000and<1/1000,veryrare

<1/10,000.

Bloodandlymphaticsystemdisorders

Veryrare:Anaemia,luekopenia,thrombocytopenia

Immunesystemdisorders

Rare:Anaphylaxis

Psychiatricandnervoussystemdisorders

Common:Headache,dizziness

Veryrare:Agitation,confusion,tremor,ataxia,dysarthria,hallucinations,psychoticsymptoms,convulsions,

somnolence,encephalopathy,coma

Theaboveeventsarereversibleandusuallyreportedinpatientswithrenalimpairmentinwhomthedosagewasin

excessofthatrecommended,orwithotherpredisposingfactors.

Respiratory,thoracicandmediastinaldisorders

Rare:Dyspnoea

Gastrointestinaldisorders

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Hepato-biliarydisorders

Rare:Reversiblerisesinbilirubinandliverrelatedenzymes

Veryrare:Hepatitis,jaundice

Skinandsubcutaneoustissuedisorders

Common:Pruritus,rashes(includingphotosensitivity)

Uncommon:Urticaria,Accelerateddiffusehairloss

Accelerateddiffusehairlosshasbeenassociatedwithawidevarietyofdiseaseprocessesandmedicines,the

relationshipoftheeventtoaciclovirtherapyisuncertain.

Rare:Agnioedema

Renalandurinarydisorders

Rare:Increasesinbloodureaandcreatinine

Veryrare:Acuterenalfailure,renalpain

Renalpainmaybeassociatedwithrenalfailure

Generaldisordersandadministrationsiteconditions

Common:Fatigue,fever

4.9Overdose

Symptomsandsigns:Aciclovirisonlypartlyabsorbedinthegastrointestinaltract.Patientshaveingestedoverdosesof

upto20gaciclovironasingleoccasion,usuallywithouttoxiceffects.

Accidental,repeatedoverdosesoforalacicloviroverseveraldayshavebeenassociatedwithgastrointestinaleffects

(suchasnauseaandvomiting)andneurologicaleffects(headacheandconfusion).

Overdosageofintravenousaciclovirhasresultedinelevationsofserumcreatinine,bloodureanitrogenandsubsequent

renalfailure.Neurologicaleffectsincludingconfusion,hallucinations,agitation,seizureandcomahavebeendescribed

inassociationwithintravenousoverdosage.

Management:Patientsshouldbeobservedcloselyforsignsoftoxicity.Haemodialysissignificantlyenhancesthe

removalofaciclovirfromthebloodandmay,therefore,beconsideredamanagementoptionintheeventof

symptomaticoverdose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:JO5AB

Modeofaction

Aciclovirisasynthetic,purinenucleosideanalogue,structurallyrelatedtoguanine,within-vitroandin-vivoactivity

againstherpessimplexvirus,types1and2,andvaricella-zostervirus.Thisactivityisduetointracellularconversion

ofaciclovirbythymidinekinasetothemonophosphate,whichisthenconvertedtothediphosphateandultimatelythe

active,triphosphatebynormalcellularenzymes.ThisforminhibitsviralDNAsynthesisandreplicationby

incorporationandalsobyinhibitionofDNApolymerase.Theprocessishighlyselectiveforinfectedcells;uninfected

cellsdonotuseaciclovirasasubstrate,thereforetoxicitytomammalianhostcellsislow.Aciclovirtriphosphateis

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Studiesinanimalsandinvitroshowvarioussensitivities,butdemonstratethatthesevirusesareinhibitedby

concentrationsofaciclovirthatareeasilyachievedclinically.AciclovirisactiveagainstDNAviruses,particularlythe

herpesviruses(simplexandvaricella-zoster).Itisparticularlyactiveagainstherpessimplexvirustypes1and2;

varicella-zostervirusislesssensitive.

Aciclovirhasnoactivityagainstlatentviruses,butthereissomeevidencethatitinhibitslatentherpessimplexvirusat

anearlystageofreactivation.

Clinicalisolatesfromsomeseverelyimmunocompromisedpatientswhohavereceivedlong-termtherapyorrepeated

coursesofaciclovirhaveshownreducedsensitivitytothedrug.Mostoftheseclinicalisolateshadreducedlevelsof

thymidinekinase;althoughisolateswithalteredthymidinekinaseorviralDNApolymerasehavebeenobserved.The

samephenomenonhasbeenobservedafterinvitroexposureofherpesvirussamplestoaciclovir.

5.2Pharmacokineticproperties

Approximately15-30%ofanoraldoseofaciclovirisabsorbedandthetimetoreachpeakconcentrationis1.5to2

hours,adoseof200mgaciclovir,everyfourhoursbymouthwasreportedtoproducemaximumandminimumsteady

stateplasmaconcentrationsof0.7and0.4 µ g/mlrespectively;equivalentvaluesfollowing400mgand800mgdoses

were1.2and0.6 µ g/mland1.8and0.9 µ g/mlrespectively.

Acicloviriswidelydistributedtotissuesandbodyfluidsincludingbrain,kidney,lungs,liver,muscle,spleen,

uterus,vaginalmucosa,vaginalsecretions,theCSFwhereconcentrationsofapproximatelyhalfthoseinplasma

areachieved,andherpeticvesicularfluid.Thedrugis9to33%boundtoplasmaproteins.Aciclovircrossesthe

placentaandisexcretedinbreastmilkatconcentrations3-4timeshigherthancorrespondingvaluesinmaternal

serum.

Afterintravenousadministration,themajorityofadoseisexcretedunchangedintheurinewithapproximately

14%appearingastheinactivemetabolite,9-carboxymethoxymethylguanine.Faecalexcretionmayaccountfor

about2%ofadose.Aciclovirisexcretedbybothtubularsecretionandglomerularfiltration;thereforeaciclovir

clearanceisapproximatelythreetimesgreaterthancreatinineclearance.Prioradministrationofprobenecid

increasesthehalflifeandtheareaundertheplasma-concentration-timecurve.Theterminalhalf-lifeis

approximately2to3hoursinadultswithnormalrenalfunction.Asrenalfunctiondeclines,agreaterpercentage

ofthedrugiseliminatedbyhepaticmetabolism.Inchronicrenalfailurethehalf-lifeisprolongedandmayreach

19.5hoursinanuricpatients.Thedrugisremovedbyhaemodialysisandthehalf-lifemaybereducedto5.7

hours,with60%ofadosebeingremovedin6hours.

Inelderlypatients,aciclovirtotalbodyclearancefallsinlinewithreducedcreatinineclearance,althoughthereappears

tobelittlechangeintheterminalplasmahalflife.

5.3Preclinicalsafetydata

Thepharmacologicalandtoxicologicalpropertiesofaciclovirarewellestablished.Therearenoadditionaldatafrom

preclinicalstudiesofclinicalconcern.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

MagnesiumStearate

MicrocrystallineCellulose

SodiumStarchGlycolate

PregelatinisedMaizeStarch

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6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

BlistercomprisingplainaluminiumfoilandPVDCcoatedPVCfilm.

Packsizes:25tabletspercarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLimited,

Spafield,

CorkRoad,

Cashel,

Co.Tipperary.

8MARKETINGAUTHORISATIONNUMBER

PA408/53/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 27 th

May1999

Dateoflastrenewal: 27 th

May2009

10DATEOFREVISIONOFTHETEXT

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