Acihexal 250mg

Main information

  • Trade name:
  • Acihexal 250mg Powder for infusion
  • Dosage:
  • 250 mg
  • Pharmaceutical form:
  • Powder for infusion
  • Units in package:
  • Vial, glass, type 1/chlorobutyl rubber seal x 5, 1250 mg
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Quimica Sintetica SA

Documents

Localization

  • Available in:
  • Acihexal 250mg Powder for infusion
    New Zealand
  • Language:
  • English

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 9515
  • Authorization date:
  • 10-12-1999
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

1

NEWZEALANDDATASHEET

Acihexal

Aciclovir,powderforinfusion,250mgand500mg

Presentation

Acihexalisawhitecrystallinefreezedriedpowderasepticallyfilledinto25mlglassvials.

-Acihexal250mgcontainssterileaciclovir250mg.

-Acihexal500mgcontainssterileaciclovir500mg.

Uses

Actions

Pharmacotherapeuticgroup

J05AB01-Directactingantivirals, nucleosidesandnucleotidesexcludingreversetranscriptase

inhibitors,aciclovir.

Mechanismofaction

Aciclovirisasyntheticpurinenucleosideanaloguewithinvitroandinvivoinhibitoryactivityagainst

humanherpesviruses,includingHerpessimplexvirustypes1and2,Varicellazostervirus(VZV),

EpsteinBarrvirus(EBV)andCytomegalovirus(CMV).Incellculture,aciclovirhasthegreatest

antiviralactivityagainstHSV-1,followed(indecreasingorderofpotency)byHSV-2,VZV,EBVand

CMV.

Pharmacodynamiceffects

TheinhibitoryactivityofaciclovirforHSV-1,HSV-2,VZVandEBVishighlyselective.Theantiviral

activityofaciclovirisattributedtothephosphorylatedcellularmetabolite,aciclovirtriphosphate.In

uninfectedcells,theenzymethymidinekinasedoesnotuseaciclovireffectivelyasasubstrate

therebylimitingtheconversiontoaciclovirtriphosphateandcellularDNApolymeraseisnotvery

sensitivetotheactivecompoundhencetoxicitytomammalianhostcellsislow.However,thymidine

kinaseencodedbyHSV,VZVandEBVconvertsaciclovirtoaciclovirmonophosphate,anucleoside

analogue,whichisfurtherphosphorylatedtothediphosphateandfinallytothetriphosphateby

cellularenzymes.AciclovirtriphosphateinterfereswiththeviralDNApolymeraseandinhibitsviral

DNAreplicationwithresultantchainterminationfollowingitsincorporationintotheviralDNA.

Prolongedorrepeatedcoursesofaciclovirinseverelyimmune-compromisedindividualsmayresultin

theselectionofvirusstrainswithreducedsensitivity,whichmaynotrespondtocontinuedaciclovir

treatment.Mostoftheclinicalisolateswithreducedsensitivityhavebeenrelativelydeficientinviral

thymidinekinase;however,strainswithalteredviralthymidinekinaseorviralDNApolymerasehave

alsobeenreported.InvitroexposureofHSVisolatestoaciclovircanalsoleadtotheemergenceof

lesssensitivestrains.TherelationshipbetweentheinvitrodeterminedsensitivityofHSVisolatesand

clinicalresponsetoaciclovirtherapyisnotclear.Allpatientsshouldbecautionedtoensuretheyavoid

thepotentialofvirustransmission,particularlywhenactivelesionsarepresent.

Pharmacokinetics

Absorption

Inadults,meansteadystatepeakplasmaconcentrations(Cssmax)followingaone-hourIVinfusion

of2.5mg/kg,5mg/kg,10mg/kgand15mg/kgwere5.1mcg/ml,9.8mcg/ml,20.7mcg/mland23.6

2

mcg/ml,respectively.Thecorrespondingtroughlevels(Cssmin)7hourslaterwere0.5mcg/ml,0.7

mcg/ml,2.3mcg/mland2.0mcg/ml,respectively.Inchildrenover1yearofagesimilarmeanpeak

(Cssmax)andtrough(Cssmin)levelswereobservedwhenadoseof250mgpersquaremetrebody

surfaceareawassubstitutedfor5mg/kgandadoseof500mgpersquaremetrebodysurfacearea

wassubstitutedfor10mg/kg.

Distribution

Cerebrospinalfluidlevelsareapproximately50%ofcorrespondingplasmalevels.Plasmaprotein

bindingisrelativelylowat9to33%anddruginteractionsinvolvingbindingsitedisplacementarenot

anticipated.

Biotransformation

9-carboxymethoxymethylguanineisthemajormetaboliteofaciclovirandaccountsfor10to15%of

thedoseexcretedintheurine.

Elimination

Inadultstheterminalplasmahalf-lifeofaciclovirafterintravenousadministrationisabout2.9hours.

Approximately60%ofthemedicineisexcretedunchangedbythekidneybyglomerularfiltrationand

tubularsecretion.Whenaciclovirisgivenonehourafter1gofprobenecidtheterminalhalf-lifeand

theareaundertheplasmaconcentrationtimecurveareextendedby18%and40%,respectively.

Inpatientswithchronicrenalfailurethemeanterminalhalflifewasfoundtobe19.5hours.Themean

aciclovirhalflifeduringhaemodialysiswas5.7hours.Plasmaaciclovirlevelsdroppedapproximately

60%duringdialysis.

Specialpatientconsiderations

Inneonatesagedupto3monthstreatedwithdosesof10mg/kgIVoveraone-hourperiodevery8

hourstheCssmaxwas13.8mcg/mlandtheCssminwas2.3mcg/ml.Theterminalplasmahalflifein

thesepatientswas3.8hours.Intheelderlytotalbodyclearancefallswithincreasingage,associated

withdecreasesincreatinineclearance,althoughthereislittlechangeintheterminalplasmahalflife.

Indications

TreatmentofHerpessimplexinfections.

ProphylaxisofHerpessimplexinfectionsinimmune-compromisedpatients.

TreatmentofVaricellazosterinfections.

TreatmentofHerpessimplexinfectionsintheneonate.

ProphylaxisofCMVinfectioninbonemarrowtransplantrecipients.Ithasbeenshownthathighdose

intravenousaciclovirreducestheincidenceanddelaystheonsetofCMVinfection.Whenhighdose

intravenousaciclovirisfollowedby6monthstreatmentwithhighdoseoralaciclovir(refertoseparate

prescribinginformationfororalaciclovir)mortalityandtheincidenceofviraemiaarealsoreduced.

Dosageandadministration

Dosage

Adults

Obesepatientsshouldbedosedattherecommendedadultdoseusingidealbodyweight,ratherthan

actualbodyweight.

PatientswithHerpessimplex(exceptherpesencephalitis)orVaricellazosterinfectionsshouldbe

3

givenintravenousaciclovirindosesof5mg/kgbodyweightevery8hours.

Immune-compromisedpatientswithVaricellazosterinfectionsorpatientswithherpesencephalitis

shouldbegivenintravenousaciclovirindosesof10mg/kgbodyweightevery8hoursprovidedrenal

functionisnotimpaired.

ForprophylaxisofCMVinfectioninbonemarrowtransplantrecipientsaciclovir500mgpersquare

metrebodysurfaceareashouldbegivenintravenously3timesdailyatapproximately8hourly

intervals.Thedurationoftreatmentrecommendedinbonemarrowtransplantrecipientsisfrom5days

beforetransplanttoupto30daysaftertransplant.

Children

Thedoseofintravenousaciclovirforchildrenagedbetween3monthsand12yearsiscalculatedon

thebasisofbodysurfacearea.

ChildrenwithHerpessimplex(exceptherpesencephalitis)orVaricellazosterinfectionsshouldbe

givenintravenousaciclovirindosesof250mgpersquaremetrebodysurfaceareaevery8hours.

Inimmune-compromisedchildrenwithVaricellazosterinfectionsorchildrenwithherpesencephalitis,

intravenousaciclovirshouldbegivenindosesof500mgpersquaremetrebodysurfaceareaevery8

hoursifrenalfunctionisnotimpaired.

LimiteddatasuggestthatfortheprophylaxisofCMVinfectioninchildren,over2yearsofage,who

haveundergonebonemarrowtransplantation,theadultdosemaybegiven.

Childrenwithimpairedrenalfunctionrequireanappropriatelymodifieddose,accordingtothedegree

ofimpairment.

Neonates

Thedosageofintravenousaciclovirinneonatesiscalculatedonthebasisofbodyweight.

NeonateswithHerpessimplexinfectionsshouldbegivenintravenousaciclovirindosesof10mg/kg

bodyweightevery8hours.

Elderlypatients

Thepossibilityofrenalimpairmentintheelderlymustbeconsideredandthedosageshouldbe

adjustedaccordingly(refertoDosageinrenalimpairmentbelow).Adequatehydrationshouldbe

maintained.

Dosageinrenalimpairment

Cautionisadvisedwhenadministeringintravenousaciclovirtopatientswithimpairedrenalfunction.

Thefollowingadjustmentsindosagearesuggested.Adequatehydrationshouldbemaintained.

Creatinineclearance Dosage

25to50ml/min Thedoserecommendedabove(5or10mg/kgbodyweightor500mgper

squaremetrebodysurfacearea)shouldbegivenevery12hours.

10to25ml/min Thedoserecommendedabove(5or10mg/kgbodyweightor500mgper

squaremetrebodysurfacearea)shouldbegivenevery24hours.

0(anuric)to10

ml/min Inpatientsreceivingcontinuousambulatoryperitonealdialysis(CAPD)the

doserecommendedabove(5or10mg/kgbodyweightor500mgpersquare

metrebodysurfacearea)shouldbehalvedandadministeredevery24hours.

Inpatientsreceivinghaemodialysisthedoserecommendedabove(5or10

4

Creatinineclearance Dosage

mg/kgbodyweightor500mgpersquaremetrebodysurfacearea)shouldbe

halvedandadministeredevery24hoursandafterdialysis.

Acourseoftreatmentwithintravenousaciclovirusuallylasts5days,butthismaybeadjusted

accordingtothepatient'sconditionandresponsetotherapy.Treatmentforherpesencephalitisand

neonatalHerpessimplexinfectionsusuallylasts10days.

Thedurationofprophylacticadministrationofintravenousaciclovirisdeterminedbythedurationof

theperiodatrisk.

Administration

Therequireddoseofaciclovirshouldbeadministeredbyslowintravenousinfusionoveraonehour

period.

Acihexalpowderforinfusionshouldbereconstitutedin10mlofeitherWaterforInjectionsBPor

SodiumChlorideInjectionBP(0.9%w/v)toprovideasolutioncontaining25mgaciclovirperml.From

thecalculateddose,determinetheappropriatenumberofvialstobeused.Toreconstituteeachvial,

addtherecommendedvolumeofinfusionfluidandshakegentlyuntilthecontentsofthevialhave

dissolvedcompletely.

Reconstitutedaciclovirintravenousinfusionmaybeadministeredbyacontrolled-rateinfusionpump.

Alternatively,thereconstitutedsolutionmaybefurtherdilutedtogiveanaciclovirconcentrationofnot

greaterthan5mg/ml(0.5%w/v)foradministrationbyinfusion.Addtherequiredvolumeof

reconstitutedsolutiontothechoseninfusionsolution,asrecommendedbelow,andshakewellto

ensureadequatemixingoccurs.

Forchildrenandneonates,whereitisadvisabletokeepthevolumeofinfusionfluidtoaminimum,it

isrecommendedthatdilutionisonthebasisof4mlreconstitutedsolution(100mgaciclovir)addedto

20mlofinfusionfluid.

Foradults,itisrecommendedthatinfusionbagscontaining100mlofinfusionfluidareused,even

whenthiswouldgiveanaciclovirconcentrationsubstantiallybelow0.5%w/v.Thusone100ml

infusionbagmaybeusedforanydosebetween250mgand500mgaciclovir(10and20mlof

reconstitutedsolution)butasecondbagmustbeusedfordosesbetween500and1000mg.

Whendilutedinaccordancewiththerecommendedschedules,aciclovirintravenousinfusionisknown

tobecompatiblewiththefollowinginfusionfluidsandstableforupto12hoursatroomtemperature

(15°Cto25°C):SodiumChlorideIntravenousInfusionBP(0.45%and0.9%w/v);SodiumChloride

(0.18%w/v)andGlucose(4%w/v)IntravenousInfusionBP;SodiumChloride(0.45%w/v)and

Glucose(2.5%w/v)IntravenousInfusionBP;CompoundSodiumLactateIntravenousInfusionBP

(Hartmann'sSolution).Aciclovirintravenousinfusionwhendilutedinaccordancewiththeabove

schedulewillgiveanaciclovirconcentrationnotgreaterthan0.5%w/v.

Sincenoantimicrobialpreservativeisincluded,reconstitutionanddilutionmustbecarriedoutunder

fullasepticconditions,immediatelybeforeuse,andanyunusedsolutiondiscarded.

Shouldanyvisibleturbidityorcrystallisationappearinthesolutionbeforeorduringinfusion,the

preparationshouldbediscarded.

5

Contraindications

Knownhypersensitivitytoaciclovir,valaciclovirortoanyoftheinactiveingredientslistedinFurther

information.

Warningsandprecautions

Thismedicineisintendedforintravenousinfusiononlyandshouldnotbeusedbyanyotherroute.

ReconstitutedaciclovirintravenousinfusionhasapHofapproximately11.0andshouldnotbe

administeredbymouth.

Aciclovirintravenousinfusionmustbegivenoveraperiodofatleastonehourinordertoavoidrenal

tubulardamage.Itshouldnotbeadministeredasabolusinjection.Althoughtheaqueoussolubilityof

aciclovirsodium(forinfusion)exceeds100mg/ml,precipitationofaciclovircrystalsinrenaltubules,

andtheconsequentrenaltubulardamage,canoccurifthemaximumsolubilityoffreeaciclovir(2.5

mg/mlat37°Cinwater)isexceeded.Theinfusionmustbeaccompaniedbyadequatehydration.

Sincemaximumurineconcentrationoccurswithinthefirstfewhoursfollowinginfusion,particular

attentionshouldbegiventoestablishsufficienturineflowduringthatperiod.Concomitantuseofother

nephrotoxicmedicines,pre-existingrenaldiseaseanddehydrationincreasetheriskoffurtherrenal

impairmentbyaciclovir.

Asaciclovirhasbeenassociatedwithreversibleencephalopathicchanges,itshouldbeusedwith

cautioninpatientswithunderlyingneurologicalabnormalities,significanthypoxiaorseriousrenal,

hepaticorelectrolyteabnormalities.Itshouldalsobeusedwithcautioninpatientswhohave

manifestedneurologicalreactionstocytotoxicmedicinesorarereceivingconcomitantlyinterferonor

intrathecalmethotrexate.

Resistantstrainshavebeenisolatedinvitroandinanimalsfollowingtreatmentwithaciclovir.HSV

strainsresistantinvitrotoaciclovirhavealsobeenisolatedfromimmunocompromisedpatients

receivingaciclovirforherpessimplexinfections.Thereforethepotentialforthedevelopmentof

resistantHSVstrainsinpatientstreatedwithaciclovirshouldbeborneinmind.Therelationship

betweeninvitrosensitivityofherpesvirusestoaciclovirandclinicalresponsetotherapyhasyettobe

established.

Useinpatientswithrenalimpairmentandinelderlypatients

Intravenousacicloviriseliminatedbyrenalclearance,thereforethedosemustbereducedinpatients

withrenalimpairmenttoavoidaccumulationofaciclovirinthebody(refertoDosageand

administration).Elderlypatientsarelikelytohavereducedrenalfunctionandthereforetheneedfor

dosereductionmustbeconsideredinthisgroupofpatients.Bothelderlypatientsandpatientswith

renalimpairmentareatincreasedriskofdevelopingneurologicalsideeffectsandshouldbeclosely

monitoredforevidenceoftheseeffects.Inthereportedcases,thesereactionsweregenerally

reversibleondiscontinuationoftreatment(refertoAdverseeffects).

Inpatientsreceivingintravenousaciclovirathigherdoses(e.g.forherpesencephalitis),specificcare

regardingrenalfunctionshouldbetaken,particularlywhenpatientsaredehydratedorhaveanyrenal

impairment.

Pregnancyandlactation

Useinpregnancy

AssignedCategoryB3bytheAustralianDrugEvaluationCommittee.Thiscategoryincludes

medicineswhichhavebeentakenbyonlyalimitednumberofpregnantwomenandwomenof

childbearingage,withoutanincreaseinthefrequencyofmalformationorotherdirectorindirect

harmfuleffectsonthehumanfoetushavingbeenobserved.Studiesinanimalshaveshownevidence

ofanincreasedoccurrenceoffoetaldamage,thesignificanceofwhichisconsidereduncertainin

humans.

6

Animalstudiesshowthataciclovirreadilydiffusesacrosstheplacenta.Systemicadministrationof

aciclovirininternationallyacceptedstandardtestsdidnotproduceembryotoxicorteratogeniceffects

inrabbits,ratsormice.Aciclovirwasnotteratogenicinthemouse(450mg/kg/dayorally),rabbit(50

mg/kg/daysubcutaneouslyandintravenously)orrat(50mg/kg/daysubcutaneously)whendosed

throughouttheperiodofmajororganogenesis.Thisexposureintheratresultedinplasmalevels

similartothemeansteadystatepeakconcentrationinhumansafteronehourinfusionsof10mg/kg

everyeighthours.Inadditionalstudiesinwhichratsweregiventhreesubcutaneousdosesofaciclovir

100mg/kgongestationday10,foetalabnormalities,e.g.headandtailanomalies,werereported

howeveraciclovirexposurewasfivetimesthehumanlevelsafter10mg/kginfusions).Theclinical

relevanceofthesefindingsisuncertain.

Apost-marketingaciclovirpregnancyregistryhasdocumentedpregnancyoutcomesinwomen

exposedtoanyformulationofaciclovir.Theregistryfindingshavenotshownanyincreaseinthe

numberofbirthdefectsamongstaciclovirexposedsubjectscomparedwiththegeneralpopulation,

andanybirthdefectsshowednouniquenessorconsistentpatterntosuggestacommoncause.The

useofintravenousaciclovirshouldbeconsideredonlywhenthepotentialbenefitsoutweighthe

possibilityofunknownrisks.Ifsuppressivetherapyisusedintheperinatalperioditshouldnotbe

assumedthatviralsheddinghasceased,orthattherisktofoetusorneonatehasdecreased.

Useinlactation

Followingoraladministrationof200mgaciclovirfivetimesaday,aciclovirhasbeendetectedin

humanbreastmilkatconcentrationsrangingfrom0.6to4.1timesthecorrespondingplasmalevels.

Theselevelswouldpotentiallyexposenursinginfantstoaciclovirdosagesofupto0.3mg/kg

bodyweight/day.CautionisthereforeadvisedifZOVIRAXistobeadministeredtoanursing

woman.

Effectsonabilitytodriveandusemachines

Thismedicineispresumedtobesafeorunlikelytoproduceaneffect.Aciclovirpowderforinfusionis

generallyusedinahospitalsettingandinformationonabilitytodriveandoperatemachineryisnot

usuallyrelevant.Therehavebeennostudiestoinvestigatetheeffectofaciclovirondriving

performanceortheabilitytooperatemachinery.

Other

Preclinicalsafetydata

Animalstudiesindicatethatathighdosesacicloviriscytotoxic.

Mutagenesis

AciclovirwasclastogenicinChinesehamstercellsinvivoatexposurelevelsalsocausing

nephrotoxicity(500and1000mg/kgparenteraldose).Therewasalsoanincrease,thoughnot

statisticallysignificant,inchromosomaldamageatmaximumtolerateddoses(100mg/kg)ofaciclovir

inrats.Noactivitywasfoundinadominantlethalstudyinmiceorinfourmicrobialassays.Positive

resultswereobtainedintwoofsevengenetictoxicityassaysusingmammaliancellsinvitro(positive

inhumanlymphocytesinvitroandonelocusinmouselymphomacells,negativeattwootherlociin

mouselymphomacellsandthreelociinaChinesehamsterovarycellline).Theresultsofthese

mutagenicitytestsinvitroandinvivosuggestthataciclovirisunlikelytoposeageneticthreatto

humansattherapeuticdoselevels.

Carcinogenesis

Aciclovirwaspositiveinoneoftwomousecelltransformationsystemsinvitro.Inoculationofthe

transformedcellsintoimmunesuppressedmiceresultedintumours.Thesedataaresuggestiveofan

oncogenicpotential.However,thevalidityofthistypeofstudyisunclear.

Lifetimeoraldosingstudiesinmiceandratsgavenoevidencefortumorigenicitybutinthesespecies

theabsorptionoforalaciclovirispoorandpossiblyself-limiting.

7

Effectonfertility

Thereisnoexperienceoftheeffectofintravenousaciclovironhumanfertility.Theresultsofstudies

inanimalsindicatethataciclovirshouldhavenoeffectonfertilityinhumansattherapeuticdoses.

Adverseeffects

Thefrequencycategoriesassociatedwiththeadverseeventsbelowareestimates.Formostevents,

suitabledataforestimatingincidencewerenotavailable.Inaddition,adverseeventsmayvaryintheir

incidencedependingontheindication.

Thefollowingconventionhasbeenusedfortheclassificationofundesirableeffectsintermsof

frequency:verycommon1in10ormore,commonbetween1in100and1in10,uncommonbetween

1in1000and1in100,rarebetween1in10,000and1in1000,veryrare<1/10,000.

Bloodandlymphaticsystemdisorders

Uncommon-decreasesinhaematologicalindices(anaemia,thrombocytopenia,leukopenia).

Immunesystemdisorders

Veryrare-anaphylaxis.

Psychiatricandnervoussystemdisorders

Common-lethargy,obtundation.

Veryrare-headache,dizziness,agitation,confusion,tremor,ataxia,dysarthria,hallucinations,

psychoticsymptoms,convulsions,somnolence,encephalopathy,coma.Theaboveeventsare

generallyreversibleandusuallyreportedinpatientswithrenalimpairmentorwithotherpredisposing

factors(refertoWarningsandprecautions).

Vasculardisorders

Common-phlebitis.

Respiratory,thoracicandmediastinaldisorders

Veryrare-dyspnoea.

Gastrointestinaldisorders

Common-nausea,vomiting.

Veryrare-diarrhoea,abdominalpain.

Hepatobiliarydisorders

Common-reversibleincreasesinliver-relatedenzymes.

Veryrare-reversibleincreasesinbilirubin,jaundice,hepatitis.

Skinandsubcutaneoustissuedisorders

Common-pruritus,urticaria,rashes(includingphotosensitivity).

Veryrare-angioedema.

Renalandurinarydisorders

Common-increasesinbloodureaandcreatinine.Rapidincreasesinbloodureaandcreatininelevels

arebelievedtoberelatedtothepeakplasmalevelsandthestateofhydrationofthepatient.Toavoid

thiseffectaciclovirshouldnotbegivenasanintravenousbolusinjectionbutbyslowinfusionovera

onehourperiod.

8

Veryrare-renalimpairment,acuterenalfailure,renalpain.Adequatehydrationshouldbe

maintained.Renalimpairmentusuallyrespondsrapidlytorehydrationofthepatientand/ordosage

reductionorwithdrawalofthedrug.Progressiontoacuterenalfailure,however,canoccurin

exceptionalcases.Renalpainmaybeassociatedwithrenalfailure.

Liver

Veryrare:hepatitisandjaundice.

Generaldisordersandadministrationsiteconditions

Veryrare-fatigue,fever,localinflammatoryreactions

Severelocalinflammatoryreactionssometimesleadingtobreakdownoftheskinhaveoccurredwhen

aciclovirhasbeeninadvertentlyinfusedintoextracellulartissues.

Others

Uncommon:diaphoresis,haematuria,hypotensionandheadache.

Interactions

Noclinicallysignificantinteractionshavebeenidentified.

Acicloviriseliminatedprimarilyunchangedintheurineviaactiverenaltubularsecretion.Any

medicinesadministeredconcurrentlythatcompetewiththismechanismoraffectrenalphysiology

mayincreaseaciclovirplasmaconcentrations.ProbenecidandcimetidineincreasetheAUCof

aciclovirbythismechanism,andreduceaciclovirrenalclearance.Howevernodosageadjustmentis

necessarybecauseofthewidetherapeuticindexofaciclovir.

Inpatientsreceivingintravenousaciclovir,cautionisrequiredduringconcurrentadministrationwith

medicineswhichcompetewithaciclovirforelimination,becauseofthepotentialforincreasedplasma

levelsofoneorbothmedicinesortheirmetabolites.IncreasesinplasmaAUCsofaciclovirandofthe

inactivemetaboliteofmycophenolatemofetil,animmunosuppressantagentusedintransplant

patients,havebeenshownwhenthemedicinesarecoadministered.

Careisalsorequired(withmonitoringforchangesinrenalfunction)ifadministeringintravenous

aciclovirwithmedicineswhichaffectotheraspectsofrenalphysiology(e.g.cyclosporin,tacrolimus).

Inpatientsover60yearsofageconcurrentuseofdiureticsincreasesplasmalevelsofaciclovirvery

significantly.Itisnotknownwhetherasimilareffectoccursinyoungadults.

Inpatientsreceivingzidovudinenosignificantoverallincreaseintoxicitywasassociatedwiththe

additionofaciclovir.Nodataareavailableoninteractionsbetweenaciclovirandotherantiretroviral

therapies.

Aciclovirshouldalsobeusedwithcautioninpatientswhohavemanifestedneurologicalreactionsto

cytotoxicmedicinesorarereceivingconcomitantlyinterferonorintrathecalmethotrexate.

9

Overdosage

Signsandsymptoms

Overdosageofintravenousaciclovirhasresultedinelevationsofserumcreatinine,bloodurea

nitrogenandsubsequentrenalfailure.Neurologicaleffectsincludingconfusion,hallucinations,

agitation,seizuresandcomahavebeendescribedinassociationwithoverdosage.

Management

Adequatehydrationisessentialtoreducethepossibilityofcrystalformationintheurine.

Haemodialysissignificantlyenhancestheremovalofaciclovirfromthebloodandmay,therefore,be

consideredanoptioninthemanagementofoverdose.

Pharmaceuticalprecautions

Instructionsforuse/handling

Acihexalpowderforinfusioncontainsnoantimicrobialpreservative.Reconstitutionordilutionshould

thereforebecarriedouteitherunderfullasepticconditionsorimmediatelybeforeuseandanyunused

solutiondiscarded.

Acihexalpowderforinfusionshouldbereconstitutedusing10mlofeitherWaterforInjectionsBPor

SodiumChlorideInjectionBP(0.9%w/v)toprovideasolutioncontainingaciclovir25mg/ml(referto

DosageandAdministration).

Incompatibilities

Noneknown.

Specialprecautionsforstorage

Storeatorbelow25°C.Protectfromlightandmoisture.Storethereconstitutedmedicinebetween15

to25°Candusewithin12hours.Reconstitutedordilutedsolutionsshouldnotberefrigerated.

Medicineclassification

PrescriptionMedicine.

Packagequantities

Packsof5vials.Notallpacksizesand/orstrengthsmaybecurrentlymarketed.

Furtherinformation

Listofexcipients

Sodiumhydroxide.

Nameandaddress

NovartisNewZealandLimited

10

PrivateBag65904MairangiBay

AUCKLAND0754

Telephone:(09)3618100

Dateofpreparation

28 th

August2012

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Public Notification: Platinum Rhino 25000 contains hidden drug ingredient

The Food and Drug Administration is advising consumers not to purchase or use Platinum Rhino 25000, a product promoted for sexual enhancement. This product was identified during an examination of international mail shipments.

FDA - U.S. Food and Drug Administration

10-7-2018

Preventieve HIV-remmers (PrEP) worden verstrekt voor een periode van vijf jaar

Preventieve HIV-remmers (PrEP) worden verstrekt voor een periode van vijf jaar

PrEP wordt binnen een onderzoekssetting voor een periode van vijf jaar verstrekt aan de hoogrisicogroep van mannen die seks hebben met mannen (MSM). Dat heeft minister Bruno Bruins (Medische Zorg) vandaag bekend gemaakt. Op basis van schattingen van het RIVM zullen ongeveer 6500 mannen hiervan gebruik gaan maken en kunnen hiermee  250 hiv-infecties per jaar worden voorkomen. Voor gebruikers gaat een eigen bijdrage gelden van maximaal 25%, dat komt overeen met ongeveer 12 euro per maand. Ook wordt hen gev...

Netherlands - Ministerie van Volksgezondheid, Welzijn en Sport

4-5-2018

Badger Botanicals Recalls Red Suma, Green Suma, Green Hulu 2, And Red Hulu 2 Kratom Supplements Because Of Possible Salmonella Health Risk

Badger Botanicals Recalls Red Suma, Green Suma, Green Hulu 2, And Red Hulu 2 Kratom Supplements Because Of Possible Salmonella Health Risk

Badger Botanicals, LLC of Springville, Utah is recalling Green Suma, Red Suma, Green Hulu 2, and Red Hulu 2 kratom dietary supplements sold directly to consumers via the company website from January 1st, 2018 to April l 12th, 2018 in pouches of 250g, because it has the potential to be contaminated with Salmonella.

FDA - U.S. Food and Drug Administration

15-1-2014

Revocation of wholesale distribution and manufacturing authorisations granted to Singad Pharma ApS

Revocation of wholesale distribution and manufacturing authorisations granted to Singad Pharma ApS

On 20 December 2013 and on 10 January 2014, the Danish Health and Medicines Authority decided to revoke the section 39 authorisations for wholesale distribution and manufacturing of medicinal products with the authorisation IDs 25081 and 25082 granted to Singad Pharma ApS (company number 255894).

Danish Medicines Agency

10-12-2018

EU/3/17/1906 (PTC Therapeutics International Limited)

EU/3/17/1906 (PTC Therapeutics International Limited)

EU/3/17/1906 (Active substance: Recombinant adeno-associated viral vector serotype 5 carrying the gene for the human frataxin protein) - Transfer of orphan designation - Commission Decision (2018)8634 of Mon, 10 Dec 2018 European Medicines Agency (EMA) procedure number: EMA/OD/0000002509

Europe -DG Health and Food Safety

10-12-2018

EU/3/16/1786 (PTC Therapeutics International Limited)

EU/3/16/1786 (PTC Therapeutics International Limited)

EU/3/16/1786 (Active substance: Recombinant adeno-associated viral vector serotype 2 carrying the gene for the human aromatic L-amino acid decarboxylase protein) - Transfer of orphan designation - Commission Decision (2018)8630 of Mon, 10 Dec 2018 European Medicines Agency (EMA) procedure number: EMA/OD/0000002507

Europe -DG Health and Food Safety

10-12-2018

EU/3/16/1651 (PTC Therapeutics International Limited)

EU/3/16/1651 (PTC Therapeutics International Limited)

EU/3/16/1651 (Active substance: Recombinant adeno-associated viral vector serotype 9 carrying the gene for the human E6-AP ubiquitin protein ligase) - Transfer of orphan designation - Commission Decision (2018)8632 of Mon, 10 Dec 2018 European Medicines Agency (EMA) procedure number: EMA/OD/0000002508

Europe -DG Health and Food Safety

28-11-2018

PHEBURANE (Eurocept International BV)

PHEBURANE (Eurocept International BV)

PHEBURANE (Active substance: Sodium Phenylbutyrate) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)8043 of Wed, 28 Nov 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/2500/T/20

Europe -DG Health and Food Safety

30-10-2018

EU/3/14/1250 (Akcea Therapeutics UK Ltd)

EU/3/14/1250 (Akcea Therapeutics UK Ltd)

EU/3/14/1250 (Active substance: Phosphorothioate oligonucleotide targeted to transthyretin) - Transfer of orphan designation - Commission Decision (2018)7282 of Tue, 30 Oct 2018 European Medicines Agency (EMA) procedure number: EMA/OD/098/13/T/01

Europe -DG Health and Food Safety

29-10-2018

Replagal (Shire Human Genetic Therapies AB)

Replagal (Shire Human Genetic Therapies AB)

Replagal (Active substance: Agalsidase alfa) - Centralised - Yearly update - Commission Decision (2018)7250 of Mon, 29 Oct 2018

Europe -DG Health and Food Safety

3-7-2018

Samsca (Otsuka Pharmaceutical Europe Ltd)

Samsca (Otsuka Pharmaceutical Europe Ltd)

Samsca (Active substance: tolvaptan) - Centralised - 2-Monthly update - Commission Decision (2018) 4250 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/980/II/31

Europe -DG Health and Food Safety

6-6-2018

Stocrin (Merck Sharp and Dohme B.V.)

Stocrin (Merck Sharp and Dohme B.V.)

Stocrin (Active substance: efavirenz) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)3689 of Wed, 06 Jun 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/250/T/113

Europe -DG Health and Food Safety

23-4-2018

Mylotarg (Pfizer Limited)

Mylotarg (Pfizer Limited)

Mylotarg (Active substance: gemtuzumab ozogamicin) - New authorisation - Commission Decision (2018)2504 of Mon, 23 Apr 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4204

Europe -DG Health and Food Safety