DIAZEPAM

Main information

  • Trade name:
  • DIAZEPAM 5 Mg/ Ml Solution for Injection
  • Dosage:
  • 5 Mg/ Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Prescription type:
  • Product subject to prescription which may not be renewed (A)
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIAZEPAM 5 Mg/Ml Solution for Injection
    Ireland
  • Language:
  • English

Therapeutic information

  • Therapeutic area:
  • Benzodiazepine derivatives

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization status:
  • Authorised
  • Authorization number:
  • PA1339/006/001
  • Authorization date:
  • 22-05-2009
  • Last update:
  • 20-10-2016

Patient Information leaflet: composition, indications, side effects, dosage, interactions, adverse reactions, pregnancy, lactation

PACKAGELEAFLET:INFORMATIONFORTHEUSER

Diazepam5mg/mlSolutionforInjection

Diazepam5mg/ml

(RefertoasDiazepamInjectioninthisleaflet)

Readallofthisleafletcarefullybeforeyoustarttotakethismedicine.

Keepthisleaflet.Youmayneedtoreaditagainwhileyouarereceivingyourtreatment.

Ifyouhaveanyfurtherquestions,pleaseaskyourdoctororpharmacist.

Thismedicinehasbeenprescribedforyou.Donotpassitontoothers.Itmayharmthem,evenif

theirsymptomsarethesameasyours.

Ifanyofthesideeffectsgetserious,orifyounoticeanysideeffectsnotlistedinthisleaflet,

pleasetellyourdoctororpharmacist.

Inthisleaflet:

WhatDiazepamInjectionisandwhatitisusedfor

BeforeyoutakeDiazepamInjection

HowtotakeDiazepamInjection

Possiblesideeffects

HowtostoreDiazepamInjection

Furtherinformation

1. WhatDiazepamInjectionisandwhatitisusedfor

ThenameofyourmedicineisDiazepamInjection;theactiveingredientisdiazepam.Thismedicine

belongstoagroupofmedicinescalledbenzodiazepines.DiazepamInjectionisused:

totreatanxietyandagitation

asasedativeonminorsurgicaladdentalprocedures

asananticonvulsant(medicinetocontrolfits)

asamusclerelaxant

2.BeforeyoutakeDiazepamInjection

YoushouldNOTbegivenDiazepamInjectionifyou:

areallergic(hypersensitivity)todiazepam,anyotherbenzodiazepinesortoanyoftheother

ingredientsinDiazepamInjection(seesection6,Furtherinformation)

aresufferingfromphobias(irrationalfears)orobsessions

havebreathingproblems

sufferfromobstructivesleepapnoea(aconditionwhereyoustopbreathingduringsleep)

havesevereliverdisease

havesufferedrecentlossorbereavementasdiazepamcancausememoryloss

sufferfromdepression,anxietyorotherlongstandingmentalillness,forwhichyouarenotbeing

treated.

DiazepamInjectionshouldnotbeusedinprematureornewbornbabies.

TalktoyourdoctorbeforebeinggivenDiazepamInjectionifyou:

haveakidneyorliverdisease

sufferfromlungdisease

sufferfromporphyria(adiseaseofbloodproteinsaffectingtheskin,gutandnervoussystem)

sufferfrommyastheniagravis(adiseaseofthenervoussystemcausingmuscleweakness)

haveahistoryofalcoholand/ordrugabuse

sufferfrombraindisease(particularlydiseasesaffectingthebloodcirculationofthebrain)

ifyoutakeanymedicineswhichaffectthecentralnervoussystem.

CautionshouldbetakenwhengivingDiazepamInjectiontotheelderlyandcomatosepatients.

Takingothermedicines

Pleasetellyourdoctororpharmacistifyouaretakingorhaverecentlytakenanyothermedicines,

includingmedicinesobtainedwithoutprescription.Thefollowingmedicinescanaffectorbeaffected

treatmentwithDiazepamInjection:

medicinesusedtotreatbacterialinfections(e.g.erythromycin,isoniazidandrifampicin)

medicinesusedtotreatdepression(e.g.mirtazapine,fluvoxamineandfluoxetine)

medicinesusedtotreatfits(e.g.carbamazepine,phenobarbital,phenytoinandsodiumvalproate)

medicinesusedinsurgery(generalanaesthetics)andstrongpainkillers(narcoticanalgesicse.g.

fentanyl)

medicinesusedtotreatallergies,includinghayfeverandinsectbites(antihistamines)

medicinesusedtotreathighbloodpressure

medicinesusedtotreatpsychosis,schizophreniaandothermentalillnesses(e.g.onlanzapine,

clozapineandzotepine)

medicinesusedtotreatHIVinfection(e.g.amprenavir,saquinavirandritonavir)

medicinesusedtotreatanxietyandsleepdisturbance

digoxin(usedtotreatabnormalheartrhythmsandheartfailure)

disulfiram(usedtotreatalcoholism)

levodopa(usedtotreatParkinson’sDisease)

lofexidine(usedtoreducesymptomsofheroinwithdrawal)

baclofenandtizanidine(musclerelaxants)

nabilone(usedtotreatnauseaandnervepain)

oralcontraceptives(“ThePill”)

theophyllineandaminophylline(usedinasthmaandlungdiseases)

cimetidine,esomeprazoleandomeprazole(usedtotreatexcessstomachacidandulcers)

diuretics(watertablets)

nitrates,usedinthetreatmentofangina

sodiumoxybate,usedtopreventepisodesofsuddenonsetofsleep(narcolepsy)withmuscle

weakness.

TakingDiazepamInjectionwithfoodanddrink

Youshouldavoidsmokinganddrinkingalcoholwhilsttakingthismedicine.Someoftheingredients

ofcoffee(caffeine)willaffectthewayDiazepamInjectionwork.

Pregnancyandbreast-feeding

Youshouldnotusethismedicineifyouarepregnantorbreastfeeding(unlessyourdoctordecidesitis

essential).Tellyourdoctorstraightawayifyouthinkyoumaybepregnantorintendtostarta

pregnancy.

Drivingandusingmachinery

Thismedicinecanaffectyourabilitytodrive.Donotdrivewhilsttakingthismedicineuntilyouknow

howthismedicineaffectsyou.

Itmaybeanoffencetodriveifyourabilitytodrivesafelyisaffected.

ThereisfurtherinformationforpatientswhoareintendingtodriveinGreatBritain–goto

http://www.gov.uk/drug-driving-law

ImportantinformationaboutsomeoftheingredientsinDiazepamInjection

Thismedicinecontains

12.5vol%ethanol(alcohol)i.e.100mgperml,equivalentto10mlbeer,4mlwineperdose.Itis

thereforeharmfultothosesufferingfromalcoholism.Thisshouldalsobetakenintoaccountin

pregnantorbreast-feedingwomen,childrenandhighriskgroupssuchaspatientswithliver

diseaseorepilepsy.

15mg/mlofbenzylalcoholandsomustnotbegiventoprematureornewbornbabies.Itmaycause

toxicand/orallergicreactionsininfantsandchildrenuptothreeyears.

sodiumbenzoate(E211)andbenzoicacid(E210)whichmayincreasetheriskofjaundicein

newbornbabies.

0.34mmol/mlofsodium.Thisshouldbeconsideredinpatientsonacontrolledsodiumdiet.

3. HowtotakeDiazepamInjection

Yourdoctorwilldecidetherightdoseforyou.Thedosagedependsontheconditionbeingtreated,

weightandage.Ifyoudonotunderstandwhatyouarebeinggiventhenaskyourdoctorornurse.The

usualdosesareasfollows:

Adults

Insevereanxietyoracutemusclespasm:

10mggivenintoaveinorintoamuscle

Thismayberepeatedafter4hours,ifnecessary

Intetanus(lockjaw):

0.1–0.3mgperkgbodyweightgivenintoaveineveryonetofourhoursor

3–10mgperkgbodyweightgivencontinuouslyover24hoursthroughanasoduodenaltube(a

tubepassedthroughthenoseintothegut)

Inepilepticfits:

0.15–0.25mgperkgbodyweightgivenslowlyintoavein

thismayberepeatedifneededafter30-60minutes.

Sedationpriortominorsurgicalordentalprocedures:

0.1–0.2mgperkgbodyweightbyinjectionintheveinormuscle,andadjustedaccordingto

response.

Dosesintheelderlyandinthosewithkidneyorliverproblemsshouldbereducedaccordingly.

Children

Controlofepilepticfitsorfebrileconvulsions:

0.2–0.3mgperkgbodyweight(or1mgforeachyearofage)givenintoavein

dosescanberepeated,ifneededafter30-60minutes.

Sedationorasamusclerelaxant:

upto0.2mgperkgbodyweightasaninjection.

IfyoutakemoreDiazepamInjectionthanyoushould

Thismedicineisadministeredbyyourdoctorandsoyouareunlikelytobegiventoomuch.

IfyoustoptakingDiazepamInjection

Dependenceondiazepamandotherbenzodiazepinescanoccurwhenusedoveralongtimeandis

morecommoninpatientswithahistoryofdrugoralcoholabuse.Theriskofdependenceislowin

smalldosesgivenovershortperiods.Ifyouhaveneededtreatmentwithdiazepamoveralongperiod,

yourdoctorwillnotstoptreatmentimmediatelybutwillgraduallyreduceyourdoseovertimetostop

withdrawalsymptomssuchasanxiety,depression,stomachcramps,nauseaandsweating.

4. Possiblesideeffects

Likeallmedicines,DiazepamInjectioncancausesideeffects,especiallytheelderly,althoughnot

everybodygetsthem.

Ascanhappenwithanymedicine,afewpeoplemaydevelopanallergicreaction.Ifyouexperience

anyofthefollowing,tellyourdoctorimmediately:

rash,itching,swellingofthefaceandeyes,difficultybreathing,seriousillnesswithblisteringof

theskin,mouth,eyesandgenitals.Thesideeffectsofdiazepamareusuallymildandinfrequent.

Sideeffectsthathavebeenreportedare:

Possiblesideeffectsarelistedbelowunderthepartsofthebodythatmightbeaffected.

Blood

changestobloodcells

Psychiatricdisorders

hallucinations(seeingorhearingthingsthatarenotthere)

sleepproblemsandnightmare

feelingexcitedoroveranxious

aggression

restlessnessandagitation

depression

numbedemotions

NervousSystem

headaches

confusion

tremor

drowsiness

reducedalertness

slurredspeech

fatigueandahangovereffect

clumsiness

memoryloss

dizziness

unusualmovementsofmuscleofface

fits

Eyes

visualdisturbances

Ears

vertigo

Heart

lowbloodpressure

slowheartbeat

stoppageofheart

chestpain

Circulatorysystem

inflammationofveins

bloodclotsinveins(venousthrombosis)

Respiratorysystem

breathingproblems

Digestivesystem

stomachandgutproblems

nausea

drymouthorincreasedproductionofsaliva

Liver

raisedliverenzymes

jaundice(yellowingoftheskin)

Skin

itchinessandrashes

Muscles

muscleweakness

muscleachesorcramps

Kidneys

inabilitytopasswater

urinaryincontinence

Reproductivesystem

increaseinbreasttissueinmen

changeinsexdrive(libido)

inhibitionoffemaleorgasm

productionofmilkfrombreast

increasedtestosteroneinmen

Otherpartsofyourbody

painatinjectionsite

poorbloodsupplyandtissuedamage(ifdruginjectedintoartery)

Theremaybeaslightincreaseinabnormalities,particularlyharelip,inbabiesborntomothersgiven

benzodiazepinesduringthefirstthreemonthsofpregnancy.Babiesexposedtobenzodiazepines

duringpregnancymaybeslowdevelopers.

Ifamotherhasreceiveddiazepamtowardstheendofpregnancyorduringlabour,thebabymaybe

affected,withfeelingcold,floppiness,difficultybreathingandsuckling,orwithdrawalsymptoms.

Reportingofsideeffects

Ifyougetanysideeffects,talktoyourdoctor,pharmacistornurse.Thisincludesanypossibleside

effectsnotlistedinthisleaflet.Youcanalsoreportsideeffectsdirectlyviathenationalreporting

systemslistedbelow.

UnitedKingdom

YellowCardScheme

www.mhra.gov.uk/yellowcard

Ireland

HPRAPharmacovigilance

EarlsfortTerrace

IRL-Dublin2

Tel:+35316764971

Fax:+35316762517

Website:www.hpra.ie

e-mail:medsafety@hpra.ie

Malta

ADRReporting

www.medicinesauthority.gov.mt/adrportal

Byreportingsideeffectsyoucanhelpprovidemoreinformationonthesafetyofthismedicine.

5. HowtostoreDiazepamInjection

Keepoutofreachandsightofchildren.

DiazepamInjectionshouldnotbestoredabove25ºC.Storeintheoriginalcontainertoprotect

fromlight;donottransfertoanothercontainer.

DiazepamInjectionshouldnotbetakenafterexpirydateonthelabel;theexpirydate

referstothelastdayofthemonth,yourdoctorwillcheckthis.

Medicinesshouldnotbedisposedofviawastewaterorhouseholdwaste.Askyourpharmacisthowto

disposeofmedicinesnolongerrequired.Thesemeasureswillhelptoprotecttheenvironment.

6. Furtherinformation

WhatDiazepamInjectioncontains

Theactiveingredientis:diazepam5mg/ml

Theotheringredientsare:benzoicacid(E210),ethanol,propyleneglycol.Sodiumbenzoate(E211),

benzylalcoholandwaterforinjections.

WhatDiazepamInjectionlookslikeandthecontentofthepack

DiazepamInjectionisaclearcolourlesstoyellowsolution.Themedicineissuppliedin2mlor4ml

amberglassampoulesinacardboardoutercarton.

Otherformats:

TolistentoorrequestacopyofthisleafletinBraille,largeprintoraudiopleasecall,freeofcharge:

08001985000(UKonly)

Pleasebereadytogivethefollowinginformation:

Productname Referencenumber

Diazepam5mg/mlsolutionforinjection PL29831/0065

ThisisaserviceprovidedbytheRoyalNationalInstituteofBlindPeople.

MarketingAuthorisationHolder:WockhardtUKLtd,AshRoadNorth,Wrexham,LL139UF,UK

Manufacturer:CPPharmaceuticalsLtd,AshRoadNorth,Wrexham,LL139UF,UK

Thisleafletwaslastrevisedin08/2015.

SUMMARYOFPRODUCTCHARACTERISTICS

1.NAMEOFMEDICINALPRODUCT

Diazepam5mg/mlSolutionforInjection

2.QUALITATIVEANDQUANTITATIVECOMPOSITION

Diazepam5mg/ml

Excipients-ContainsBenzoicacid(E210)1mg/ml,Ethanol96%100mg/ml,sodiumbenzoate(E211)

49mg/ml,Benzylalcohol15mg/ml,Propyleneglycol400mg/mlandSodiumContent-0.34mmol/ml.

Forafulllistofexcipients,seesection6.1

3.PHARMACEUTICALFORM

SolutionforInjection.

Clear,colourlesstopaleyellowliquid.

4.CLINICALPARTICULARS

4.1Therapeuticindications

Diazepaminjectionmaybeusedinsevereordisablinganxietyandagitation;forthecontrolofstatus

epilepticus,epilepticandfebrileconvulsions;torelievemusclespasm;asasedativeinminorsurgical

anddentalprocedures;orothercircumstancesinwhicharapideffectisrequired.

4.2Posologyandmethodofadministration

Dosagedependsonindividualresponse,ageandweight.

Adults:

Insevereanxietyoracutemusclespasm,diazepam10mgmaybegivenintravenouslyor

intramuscularlyandrepeatedafter4hours.

Intetanus,0.1to0.3mgperkgbodyweightmaybegivenintravenouslyandrepeatedevery1-4hours;

alternatively,acontinuousinfusionof3to10mgperkgevery24hoursmaybeusedorsimilardoses

maybegivenbynasoduodenaltube.

Instatusepilepticusorepilepticconvulsions,0.15-0.25mgperkg(usually10-20mg)isgivenby

intravenousinjection.Thedosecanberepeatedifnecessaryafter30to60minutes.Oncethepatientis

controlled,recurrenceofseizuresmaybepreventedbyaslowinfusion(maximumtotaldose3mgper

kgover24hours).

Inminorsurgicalproceduresanddentistry,0.1-0.2mgperkgbyinjection(usually10-20mg)

adjustedtothepatient’srequirements.

Elderly:

Elderlyordebilitatedpatientsshouldbegivennotmorethanhalfoftheusualdose.

Hepatic/renalimpairment

Dosagereductionmayalsoberequiredinpatientswithliverorkidneydysfunction.

Children

Instatusepilepticus,epilepticorfebrileconvulsions:0.2-0.3mgperkg(or1mgperyearoflife)is

givenbyintravenousinjection.Thedosecanberepeatedifnecessaryafter30to60minutes.

Sedationormusclerelaxation:upto0.2mgperkgmaybegivenparenterally.

Neonates:

Notrecommended;dosagehasnotbeenestablishedandDiazepamInjectioncontainsbenzylalcohol

whichshouldbeavoidedininjectionstoneonates.

IMPORTANT:Inordertoreducethelikelihoodofadverseeffectsduringintravenous

administrationtheinjectionshouldbegivenslowly(1.0mlsolutionperminute).Itisadvisableto

keepthepatientsupineforatleastanhourafteradministration.Exceptinemergencies,a

secondpersonshouldalwaysbepresentduringintravenoususeandfacilitiesforresuscitation

shouldalwaysbeavailable.

Itisrecommendedthatpatientsshouldremainundermedicalsupervisionuntilatleastonehourhas

elapsedfromthetimeofinjection.Theyshouldalwaysbeaccompaniedhomebyaresponsibleadult,

withawarningnottodriveoroperatemachineryfor24hours.

Intravenousinjectionmaybeassociatedwithlocalreactionsandthrombophlebitisandvenous

thrombosismayoccur.Inordertominimisethelikelihoodoftheseeffects,intravenousinjectionsof

diazepamshouldbegivenintoalargeveinoftheantecubitalfossa.

Wherecontinuousintravenousinfusionisnecessaryitissuggestedthat2mlDiazepamInjectionis

mixedwithatleast200mlofinfusionfluidsuchasSodiumChlorideInjectionorDextroseInjection

andthatsuchsolutionsshouldbeusedimmediately.Thereisevidencethatdiazepamisadsorbedonto

plasticinfusionbagsandgivingsets.Itisthereforerecommendedthatglassbottlesshouldbeusedfor

theadministrationofdiazepambyintravenousinfusion.

4.3Contraindications

Knownsensitivitytobenzodiazepinesoranyoftheingredients

Severeoracuterespiratoryinsufficiency/depression

Sleepapnoeasyndrome

Severehepaticinsufficiency

Avoidinjectioninneonates(containsbenzylalcohol)

Diazepaminjectionshouldnotbeusedinphobicorobsessionalstatesnorbeusedaloneinthe

treatmentofdepressionoranxietyassociatedwithdepressionduetotheriskofsuicidebeing

precipitatedinthispatientgroup.DiazepamInjectionshouldnotbeusedfortheprimarytreatmentof

psychoticillness.Incommonwithotherbenzodiazepinestheuseofdiazepammaybeassociatedwith

amnesiaandDiazepamInjectionshouldnotbeusedincasesoflossorbereavementaspsychological

adjustmentmaybeinhibited.

4.4Specialwarningsandprecautionsforuse

Diazepaminjectionshouldbeusedwithcautioninpatientswithrenalorhepaticdysfunction(see4.2

PosologyandMethodofAdministration),chronicpulmonaryinsufficiency,porphyria,muscle

weakness,myastheniagravis,coma,aknownhistoryofdrugoralcoholabuse,ororganicbrain

changes,particularlyarteriosclerosis.

DiazepammayenhancetheeffectsofotherCNSdepressants;theirconcurrentuseshouldbeavoided.

ElderlyanddebilitatedpatientsaremorepronetotheCNSeffectsofbenzodiazepinesand,therefore,

lowerdosesarerequired(seesection4.2PosologyandMethodofAdministration).Benzodiazepines

shouldbeusedwithcautionintheelderlyaslongtermuseisassociatedwithanincreasedriskof

developingdementia.

Dependenceandwithdrawalsymptoms

Thedependencepotentialofdiazepamincreaseswithdoseanddurationoftreatmentandisgreaterin

patientswithahistoryofalcoholordrugabuse(see4.8UndesirableEffects).Itislowwhenlimitedto

shorttermuse.Withdrawalsymptomsmayoccurwithbenzodiazepinesfollowingnormaluseof

therapeuticdosesforonlyshortperiodsandmaybeassociatedwithphysiologicalandpsychological

sequelae(seeSection4.8Withdrawalsymptoms).Thisshouldbeconsideredwhentreatingpatientsfor

morethanafewdays;abruptdiscontinuationshouldbeavoidedandthedosereducedgradually.

Amnesia

Benzodiazepinesmayinduceanterogradeamnesia(see4.8UndesirableEffects).

Theconditionoccursmostoftenseveralhoursafteradministration.Toreducetherisk,where

appropriateandpossible,patientsshouldbeabletohaveanuninterruptedsleepof7-8hoursafter

administration.

Useinpatientswithconcomitantmentalillness

Aswithotherbenzodiazepines,extremecautionshouldbeusedifprescribingdiazepamforpatients

withpersonalitydisorders.Thedisinhibitingeffectsofbenzodiazepinesmaybemanifestedasthe

precipitationofsuicideinpatientswhoaredepressedorshowaggressivebehaviourtowardsselfand

others.

Benzylalcoholpoisoning

Thismedicinalproductcontains15mg/mlofbenzylalcohol.Thereisariskofbenzylalcohol

poisoningwithprolongeduseofhigh-doseintravenousinfusionsofdiazepaminjectioncontaining

benzylalcohol.

Benzylalcoholmaycausetoxicreactionsandanaphylactoidreactionsininfantsandchildrenupto

threeyearsold.Mustnotbegiventoprematurebabiesorneonates.

Thismedicinalproductcontainsbenzoicacidandsodiumbenzoatewhichmayincreasetheriskof

jaundiceinnewbornbabies.

Thismedicinalproductcontains0.34mmolsodiumperml.Tobetakenintoconsiderationbypatients

onacontrolledsodiumdiet.

Thismedicinalproductcontains12.5vol%ethanol(alcohol),i.e.100mgperml.

Harmfulforthosesufferingfromalcoholism.

Tobetakenintoaccountinpregnantorbreast-feedingwomen,childrenandhigh-riskgroupssuchas

patientswithliverdiseaseorepilepsy.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Alcohol:EnhancedsedationorrespiratoryorCNSdepressionwithconcomitantadministrationof

diazepam.Concomitantuseshouldbeavoided.

Generalanaestheticsandnarcoticanalgesics:Enhancedsedationorrespiratoryandcardiovascular

depression.Ifsuchcentrallyactingdepressantdrugsaregivenparenterallyinconjunctionwith

intravenousdiazepam,severerespiratoryandcardiovasculardepressionmayoccur;carefulmonitoring

isrequired.Whenintravenousdiazepamistobeadministeredconcurrentlywithanarcoticanalgesic

agent(e.g.fentanyl),itisrecommendedthatdiazepambegivenaftertheanalgesicandthatthedosebe

carefullytitratedtomeetthepatient’sneeds.Premedicationwithdiazepammaydecreasethedoseof

fentanylderivativesrequiredforinductionofanaesthesia.

Antibacterials:Agentsthatinterferewithmetabolismbyhepaticenzymes(isoniazidandtoalesser

extenterythromycin)mayreducetheclearanceofdiazepamandpotentiateitsaction.Knowninducers

ofhepaticenzymes,forexample,rifampicin,mayincreasetheclearanceofbenzodiazepinesdiazepam.

Antidepressants:EnhancedsedationorrespiratoryorCNSdepressionwithconcomitantadministration

ofmirtazapineortricyclicantidepressants.Diazepamplasmalevelsincreasedbyconcomitant

fluvoxamineorfluoxetine.

Antiepileptics:Enhancedsedationorrespiratoryandcardiovasculardepression.

Knowninducersofhepaticenzymes,forexample,carbamazepine,phenobarbitalandphenytoin,may

increasetheclearanceofbenzodiazepines,however,despiteenzymestimulation,theneteffectof

addingtheseantiepilepticscanbeaugmentationofbenzodiazepine-inducedsedation.Serumphenytoin

levelsmayrise,fallorremainunaltered.Inaddition,phenytoinmaycausediazepamserumlevelsto

fall.Concomitantsodiumvalproatemayincreaseserumlevelsofdiazepam,withassociated

drowsiness.

Antihistamines:Enhancedsedationorrespiratoryandcardiovasculardepressionwithsedative

antihistamines.

Antihypertensives:EnhancedhypotensiveeffectwithconcomitantadministrationofACEinhibitorsor

beta-blockersorcalcium-channelblockersorhydralazine.Enhancedsedativeeffectwithalpha

blockersandpossiblymoxonidine.

Antipsychotics:Enhancedsedationorrespiratoryandcardiovasculardepression.Increasedplasma

concentrationsofzotepine.Severehypotension,collapse,respiratorydepression,potentiallyfatal

respiratoryarrestandunconsciousnesshavebeenreportedinafewpatientsonbenzodiazepinesand

clozapine.Cautionisadvisedwheninitiatingclozapinetherapyinpatientstakingbenzodiazepines.

Increasedriskofhypotension,bradycardiaandrespiratorydepressionwithconcomitantadministration

ofparenteralbenzodiazepineswithintramuscularolanzapine.

Antivirals:Amprenavir,ritonavirandsaquinavirhavebeenshowntoreducetheclearanceofdiazepam

andmaypotentiateitsactions,withriskofextremesedationandrespiratorydepression–avoid

concomitantuse.

Anxiolytics:Enhancedsedationorrespiratoryandcardiovasculardepressionwithotheranxiolytics.

Digoxin:Reducedclearanceofdigoxin.

Disulfiram:hasbeenshowntoreduceclearanceandmaypotentiateactionsofbenzodiazepines.

Diuretics:Enhancedhypotensiveeffectwhenbenzodiazepinesanddiureticsareusedconcomitantly.

Dopaminergicagents:diazepammaycauseinhibitionoflevodopa.

Hypnotics:Enhancedsedationorrespiratoryandcardiovasculardepression.

Lofexidine:Enhancedsedationorrespiratoryandcardiovasculardepression.

Musclerelaxants:IncreasedCNSdepressanteffectswithbaclofenandtizanidine.

Nabilone:Enhancedsedationorrespiratoryandcardiovasculardepression.

Nicotine:Diazepammetabolismisacceleratedbysmoking.

Nitrates:Enhancedhypotensiveeffectwhenbenzodiazepinesandnitratesareusedconcomitantly.

Oralcontraceptives:Mayreducetheclearanceofdiazepamandmaypotentiateitsactions.

Sedatives:Enhancedsedationorrespiratoryandcardiovasculardepression.

Sodiumoxybate:EnhancedCNSdepressanteffectsofsodiumoxybatewithconcomitant

benzodiazepines.

Ulcer-healingdrugs:Cimetidine,omeprazoleandesomeprazolehavebeenshowntoreducethe

clearanceofdiazepamandmaypotentiateitsactions.

Xanthines:Diazepammetabolismisacceleratedbytheophylline.Sedativeeffectsofdiazepamreduced

bycaffeine.Sedativeeffectsofdiazepamreversedwithconcomitantadministrationofaminophylline

4.6Pregnancyandlactation

Thereisnoevidenceregardingthesafetyofdiazepaminpregnancy,however,diazepamandits

metabolitedesmethyldiazepamfreelycrosstheplacentaandaccumulateinthefetalcirculation.It

shouldnotbeused,especiallyinthefirstandthirdtrimesters,unlessthebenefitisconsideredto

outweightherisk.

Iftheproductisprescribedtoawomanofchildbearingpotentialsheshouldbewarnedtocontacther

physicianregardingthediscontinuanceoftheproductifsheintendstobecomeorsuspectsthatsheis

pregnant.

Theremaybeasmallincreaseintheriskofcongenitalmalformation,particularlyoralcleft,withthe

useofbenzodiazepinesinthefirsttrimester.

Inlabour,highsingledosesorrepeatedlowdoseshavebeenreportedtoproduceeffectsonthe

neonate,suchashyperbilirubinaemia,hypothermia,hypotonia,respiratorydepressionandpoor

suckling(floppyinfantsyndrome)intheneonateandirregularitiesinthefoetalheart.

Infantsborntomotherswhotakebenzodiazepineschronicallyduringthelatterstagesofpregnancy

maydevelopphysicaldependenceandmaybeatsomeriskfordevelopingwithdrawalsymptomsin

thepostnatalperiod.Asmallnumberofchildrenexposedinuterotobenzodiazepineshaveshown

slowdevelopmentintheearlyyearsbutbyfouryearsofagehaddevelopednormally.

Sincebenzodiazepinesarefoundinthebreastmilk,benzodiazepinesshouldnotbegiventobreast

feedingmothers.

4.7Effectsonabilitytodriveandusemachines

PatientstreatedwithDiazepamInjectionshouldnotdriveorusemachinery.

Thismedicinecanimpaircognitivefunctionandcanaffectapatient’sabilitytodrivesafely.This

classofmedicineisinthelistofdrugsincludedinregulationsunder5aoftheRoadofTrafficAct

1988.Whenprescribingthismedicine,patientsshouldbetold:

Themedicineislikelytoaffectyourabilitytodrive

Donotdriveuntilyouknowhowthemedicineaffectsyou

Itisanoffencetodrivewhileundertheinfluenceofthismedicine.

However,youwouldnotbecommittinganoffence(called‘statutorydefence’)if:

oThemedicinehasbeenprescribedtotreatamedicalordentalproblemand

oYouhavetakenitaccordingtotheinstructionsgivenbytheprescriberandintheinformation

providedwiththemedicineand

oItwasnotaffectingyourabilitytodrivesafely

4.8Undesirableeffects

Thesideeffectsofdiazepamareusuallymildandinfrequent.

Bloodandlymphaticsystemdisorders:Blooddyscrasiasincludingthrombocytopeniaand

agranulocytosishavebeenreportedwithdiazepam.

Immunesystemdisorders:Hypersensitivityreactions,includinganaphylaxis,arerare.

Psychiatricdisorders:Numbedemotions.Insusceptiblepatients,anunnoticeddepressionmaybecome

evident.Paradoxicalreactions(includingaggression,rage,hostility,hallucinations,nightmares,

disinhibition,euphoria,excitation,irritability,restlessness,increasedanxiety,agitation,inappropriate

behaviourandinsomnia)areknowntooccurwithbenzodiazepinesandmaybequiteseverewith

diazepam.Theyaremorelikelytooccurinchildrenandtheelderly.

Nervoussystemdisorders:ElderlyordebilitatedpatientsareparticularlysusceptibletotheCNS

effectsofbenzodiazepines.Itisrecommendedthatdosagebelimitedtothesmallesteffectivedoseand

increasedgradually,ifnecessary,todecreasethepossibilityofdevelopmentofataxia,dizziness,and

oversedation,whichmayleadtofallsandotheraccidents(see4.2Posologyandmethodof

administration).Longtermuseofbenzodiazepinesintheelderlymaybeassociatedwithanincreased

riskofdementia.Headaches,confusion,slurredspeech,tremor,reducedalertnessanddrowsiness.

Anterogradeamnesiamayoccurusingtherapeuticdoses,theriskincreasingathigherdoses(see4.4

SpecialWarningsandSpecialPrecautionsforUse).Amnesticeffectsmaybeassociatedwith

inappropriatebehaviour.Extrapyramidaleffectsandconvulsionshaveoccurredrarelywithdiazepam.

Eyedisorders:Visualdisturbances.

Earandlabyrinthdisorders:Rarely,vertigo

Cardiacdisorders:Hypotension,particularlywithhighdosage,bradycardia,chestpain.Cardiacarrest

mayoccurwithdiazepaminjection.

Vasculardisorders:Diazepaminjectionmaybeassociatedwiththrombophlebitisandvenous

thrombosis.

Respiratory,thoracicandmediastinaldisorders:Rarely,respiratorydepressionandapnoea,

particularlywithhighdosage.

Gastrointestinaldisorders:Rarely,salivationchanges,includingdrymouthorexcessivesalivationand

gastrointestinaldisturbancesincludingnausea.

Hepatobiliarydisorders:Raisedliverenzymes,jaundiceandcholestasis.

Skinandsubcutaneoustissuedisorders:SkinreactionssuchasSteven-Johnsonsyndrome,urticaria,

rash.

Musculoskeletalandconnectivetissuedisorders:Muscleweakness.

Renalandurinarydisorders:Urinaryretention,incontinence.

Reproductivesystemandbreastdisorders:Inhibitionoffemaleorgasm,changesinlibido,

gynaecomastiaandrarely,increasedprolactinlevelsandgalactorrhoea.

Plasmatestosteroneconcentrationsmaybeincreasedinmentakingdiazepam.

Generaldisordersandadministrationsiteconditions:Fatigueandahangovereffect.Diazepam

injectionmaybeassociatedwithpain.Inadvertentintra-arterialadministrationofdiazepamhas

resultedinischaemiaandtissuenecrosis.

Withdrawalsymptoms:Developmentofdependenceiscommonafterregularuse,evenintherapeutic

dosesforshortperiods,particularlyinpatientswithahistoryofdrugoralcoholabuseormarked

personalitydisorders.Discontinuationmaybeassociatedwithwithdrawalsymptomsorrebound

phenomena(see4.4SpecialWarningsandPrecautionsforUse).Symptomsofbenzodiazepine

withdrawalincludeanxiety,depression,impairedconcentration,insomnia,headache,dizziness,

tinnitus,lossofappetite,tremor,perspiration,irritability,perceptualdisturbancessuchas

hypersensitivitytophysical,visual,andauditorystimuliandabnormaltaste,nausea,vomiting,

abdominalcramps,muscleaches/cramps,palpitations,mildsystolichypertension,tachycardia,and

orthostatichypotension.

Rareandmoreseriouswithdrawalsymptomsincludemuscletwitching,confusionalorparanoid

psychosis,convulsions,hallucinations,andastateresemblingdeliriumtremens.Brokensleepwith

vividdreamsandincreasedREMsleepmaypersistforsomeweeksafterwithdrawalof

benzodiazepines.

Reportingofsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.It

allowscontinuedmonitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcare

professionalsareaskedtoreportanysuspectedadversereactionsviathenationalreportingsystem:

UnitedKingdom

YellowCardScheme

www.mhra.gov.uk/yellowcard

Ireland

HPRAPharmacovigilance

EarlsfortTerrace

IRL-Dublin2

Tel:+35316764971

Fax:+35316762517

Website:www.hpra.ie

e-mail:medsafety@hpra.ie

Malta

ADRReporting

www.medicinesauthority.gov.mt/adrportal

4.9Overdose

a)Symptoms

Thesymptomsofmildoverdosemayincludeconfusion,impairmentofconsciousnesswith

somnolenceorasleep-likestate,littleornorespiratorydepression,ataxia,dysarthria,nystagmus,

hypotension,andmuscularweakness.Cardiacrateandrhythmremainnormalintheabsenceofanoxia

orseverehypotension.

Insevereoverdose,deepcoma,orothermanifestationsofseveredepressionofbrainstemvital

functions,particularlytherespiratorycentre,mayoccur.Comausuallylastsforonlyafewhoursbut

inelderlypeopleitmaybemoreprotractedandcyclical.Benzodiazepinerespiratorydepressanteffects

aremoreseriousinpatientswithseverechronicrespiratorydisease.

Asdruglevelsfall,severeagitation,insomniaand,possibly,majorconvulsionsmaydevelop.

Benzodiazepinespotentiatetheeffectsofothercentralnervoussystemdepressants,includingalcohol.

b)Treatment

Treatmentissymptomatic.Respiration,heartrate,bloodpressureandbodytemperatureshouldbe

monitoredandsupportivemeasurestakentomaintaincardiovascularandrespiratoryfunction.

Flumazenilisindicatedtocounteractthecentraldepressiveeffectofbenzodiazepinesbutexpert

adviceisessentialsinceadverseeffectsmayoccur(e.g.convulsionsinpatientsdependenton

benzodiazepines).

Flumazenilshouldnotbeusedinmixedoverdosesorasadiagnostictest.

Flumazeniliscontraindicatedinthepresenceofdrugsthatreduceseizurethreshold(e.g.tricyclic

antidepressants).

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Diazepamisapsychotropicsubstancefromtheclassof1,4-benzodiazepineswithmarkedpropertiesof

suppressionoftension,agitationandanxietyaswellassedativeandhypnoticeffects.Inaddition,

diazepamdemonstratesmusclerelaxantandanticonvulsiveproperties.Itisusedintheshort-term

treatmentofanxietyandtensionstates,asasedativeandpremedicant,inthecontrolofmusclespasm

andinthemanagementofalcoholwithdrawalsymptoms.

Diazepambindstospecificreceptorsinthecentralnervoussystemandparticularperipheralorgans.

ThebenzodiazepinereceptorsintheCNShaveaclosefunctionalconnectionwithreceptorsofthe

GABA-ergictransmittersystem.Afterbindingtothebenzodiazepinereceptor,diazepamaugmentsthe

inhibitoryeffectofGABA-ergictransmission.

5.2Pharmacokineticproperties

Diazepamishighlylipidsolubleandcrossesthebloodbrainbarrier.Thesepropertiesqualifyitfor

intravenoususeinshorttermanaestheticproceduressinceitactspromptlyonthebrain,anditsinitial

effectsdecreaserapidlyasitisdistributedintofatdepositsandtissues.Followingtheadministrationof

anadequateintravenousdoseofdiazepam,effectiveplasmaconcentrationsareusuallyreachedwithin

5minutes(ca.150-400ng/ml).

Absorptioniserraticfollowingintramuscularadministrationandlowerpeakplasmaconcentrations

maybeobtainedthanthosefollowingoraladministration.

Diazepamisextensivelyproteinbound(95-99%).Thevolumeofdistributionisbetween0.95and2

l/kgdependingonage.Diazepamanditsmainmetabolite,N-desmethyldiazepam,crosstheplacenta

andaresecretedinbreastmilk.

Diazepamismetabolisedpredominantlyintheliver.Itsmetabolites,N-desmethyldiazepam

(nordiazepam),temazepamandoxazepam,whichappearintheurineasglucuronides,arealso

pharmacologicallyactivesubstances.

Only20%ofthemetabolitesaredetectedintheurineinthefirst72hours.

Diazepamhasabiphasichalflifewithaninitialrapiddistributionphasefollowedbyaprolonged

terminaleliminationphaseof1-2days.FortheactivemetabolitesN-desmethyldiazepam,temazepam

andoxazepam,thehalflivesare30-100hours,10-20hoursand5-15hours,respectively.

Excretionismainlyrenalandalsopartlybiliary.Itisdependentonageaswellashepaticandrenal

function.

Metabolismandeliminationintheneonatearemarkedlyslowerthaninchildrenandadults.Inthe

elderly,eliminationisprolongedbyafactorof2to4.

Inpatientswithimpairedrenalfunction,eliminationisalsoprolonged.

Inpatientswithhepaticdisorders(livercirrhosis,hepatitis),eliminationisprolongedbyafactorof2.

5.3Preclinicalsafetydata

Chronictoxicitystudieshavedemonstratednoevidenceofdruginducedchanges.

Therearenolongtermanimalstudiestoinvestigatethecarcinogenicpotentialofdiazepam.Several

investigationspointedtoaweaklymutagenicpotentialatdosesfarabovethehumantherapeuticdose.

Localtolerabilityhasbeenstudiedfollowingsingleandrepeatdoseapplicationsintotheconjunctival

sacofrabbitsandtherectumofdogs.Onlyminimalirritationwasobserved.Therewerenosystemic

changes.

Inhumansitwouldappearthattheriskofcongenitalabnormalitiesfromtheingestionoftherapeutic

dosesofbenzodiazepinesisslight,althoughafewepidemiologicalstudieshavepointedtoan

increasedriskofcleftpalate.Therearecasereportsofcongenitalabnormalitiesandmentalretardation

inprenatallyexposedchildrenfollowingoverdosageandintoxicationwithbenzodiazepines.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Benzoicacid(E210)

Ethanol

Propyleneglycol

Sodiumbenzoate(E211)

Benzylalcohol

WaterforInjections

6.2Incompatibilities

DiazepamInjectionshouldnotbemixedwithotherdrugsinthesameinfusionsolutionorthesame

syringe.

6.3Shelflife

Threeyears

Forsingleuseonly.Discardanyremainingcontents.

6.4Specialprecautionsforstorage

Keepcontainerintheoutercartontoprotectfromlight.

Donotstoreabove25°C

6.5Natureandcontentsofcontainer

AmberTypeIPhEurglassampoules(2mlor4ml)packedin10sinanouterprintedcarton.

6.6Specialprecautionsfordisposal

None

7MARKETINGAUTHORISATIONHOLDER

WockhardtUKLtd

AshRoadNorth

Wrexham

LL139UF

8MARKETINGAUTHORISATIONNUMBER(S)

PL29831/0065

PA1339/6/1

PA1339/6/2

MA154/01103

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHE

AUTHORISATION

UK:08/02/2008

Ireland:22/05/2009

Malta:29/05/2009

10DATEOFREVISIONOFTHETEXT

08/2015