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1 PRODUCTNAME

VOLTAREN®

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75mg/3mLSolutionforinjection

2 QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachampouleof3mLcontains 75mgofdiclofenacsodium.

Forthefulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Solutionforinjection.

4CLINICALPARTICULARS 

4.1 Therapeuticindications

Intramuscularinjection

Treatmentof:

 Renalcolicandbiliarycolic.

 SeveremigraineattackswhenotherformsofVoltarenareconsideredunsuitable.

Intramuscularinjection

Treatmentorpreventionofpost‐operativepaininahospitalsetting.

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4.2 Doseandmethodofadministration

Voltarenshouldonlybeprescribedwhenthebenefitsareconsideredtooutweighthepotentialrisks.

After assessing the risk/benefit ratio in each individual patient, the lowest effective dose for the

shortest possible duration should be used. Adverse effects may be minimized by using the lowest

effectivedosefortheshortestduration

necessarytocontrolsymptoms(seesection4.4). 

Dosage

Generalpopulation

Voltarensolutionforinjectionshouldnotbegivenformorethan2 days;ifnecessary,treatmentcan

becontinuedwithVoltarentabletsorsuppositories.

Specialpopulations

Paediatricpopulation

Becauseoftheirdosagestrength,theampoulesofVoltarensolutionforinjectionarenotsuitablefor

childrenandadolescents.

Geriatricpopulation

(Patientsaged65orabove)

No adjustment of the starting dose is generally required for elderly patients However, caution is

indicatedonbasicmedicalgroun ds,especiallyforfrailelderlypatientsorthosewithalowbodyweight

(seesection4.4).

Patientswithestablishedcardiovasculardiseaseorsignificantcardiovascularriskfactors

Treatment with Voltaren solution for injection is generally not recommended in patients with

establishedcardiovasculardiseaseoruncontrolledhypertension.Ifneeded,patientswithestablished

cardiovasculardisease,uncontrolledhypertensionorsignificantriskfactorsforcardiovasculardisease

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should be treated with Voltaren solution for injection only after careful consideration and only at

doses≤100mgdailyinitialtreatmentwithVoltarensolutionforinjectioncontinuese.g.withVoltaren

tabletsorsuppositoriesformorethan4weeks(seesection4.4).

Patientswithrenalimpairment

Voltaren

iscontraindicatedinpatientswithrenalfailure(seesection4.3).

No specific studieshave been carried out in patients with renal impairment, therefore, no specific

doseadjustmentrecommendationscanbemade.CautionisadvisedwhenadministeringVoltarento

patientswithrenalimpairment(seesection4.4).

Patientswithhepaticimpairment

Voltaren

iscontraindicatedinpatientswithhepaticfailure(seesection4.3).

Nospecificstudieshavebeencarriedoutinpatientswithhepa ticimpairment,therefore,nospecific

doseadjustmentrecommendationscanbemade.CautionisadvisedwhenadministeringVoltarento

patientswithmildtomode ratehepaticimpairment(seesection4.4).

MethodofAdministration

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Intramuscularinjection

Thefollowingdirectionsforintramuscularinjection mustbefollowedinordertoavoiddamagetoa

nerve or other tissue at the injection site (which may result in muscle weakness, muscle paralysis,

hypoaesthesiaandEmboliacutismedicamentosa(Nicolausyndrome)).

Thedoseis  generally one 75mgampoule daily,

givenbydeepintraglutealinjectionintotheupper

outerquadrantusingaseptictechnique.Inseverecases(e.g.colic),thedailydosecanexceptionally

be increased to two injections of 75  mg, separated by an interval of a few hours (one into each

buttock).Alternatively,oneampouleof75mgcanbe

combinedwithotherpharmaceuticalformsof

Voltaren(e.g.tablets,suppositories)uptoatotalmaximumdailydoseof150mg.

Inmigraineattacks,clinicalexperienceislimitedtoinitialuseofoneampouleof75mgadministered

assoon aspossible,followed bysuppositoriesup  to100mgonthe

samedayif required. Thetotal

doseshouldnotexceed175mgonthefirstday.

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Intravenousinfusion

Voltarensolutionforinjectionmustnotbegivenasanintravenousbolusinjection.

Immediatelybeforestartinganintravenousinfusion,Voltarensolutionforinjectionmustbediluted

withsaline0.9%orglucose5%infusionsolutionbufferedwithsodium bicarbonateaccordi ngtothe

instructionsgivenin

section6.6.

TwoalternativedosageregimensofVoltarensolutionforinjectionarerecommended.

Forthetreatmentofmoderatetoseverepost‐operativepain,75mgshouldbeinfusedcontinuously 

overaperiodof30minutesto2hours.Ifnecessary,treatmentmayberepeatedafterafewhours,

butthe

doseshouldnotexceed150mgwithinanyperiodof24hours.

Forthepreventionofpost‐operativepain,aloadingdoseof25mgto50mgshouldbeinfusedafter

surgeryover15minutesto1hour,followedbyacontinuousinfusionofabout5mgperhourup

toa

maximumdailydoseof150mg.

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4.3 Contraindications

 Knownhypersensitivitytotheactivesubstance,sodium metabisulphiteortoanyoftheexcipients

(seesection6.1).

 Activegastricorintestinalulcer,bleedingorperforation.

 Lasttrimesterofpregnancy(seesection4.6).

 Hepaticfailure.

 Renalfailure(GFR<15mL/min/1.73m

).

 Severecardiacfailure(seesection4.4).

 Like other non‐steroidal anti‐inflammatory drugs (NSAIDs), Voltaren is also contraindicated in

patientsinwhomattacksofasthma,angioedema,urticaria,oracuterhinitisareprecipitatedby

acetylsalicylicacidorotherNSAIDs.

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4.4 Specialwarningsandprecautionsforuse

General

Patients on long‐term treatment should be reviewed regularly with regards to efficacy, adverse

effects,thedevelopmentofriskfactorsandtheon‐goingneedfortherapy.Considerationshouldbe

giventomonitoringbloodpressure,haemoglobinlevelsandrenalfunction.

Cardiovascularthromboticevents

Observationalstudieshaveindicatedthatnon‐selective

NSAIDsmaybeassociatedwithanincreased

riskofseriouscardiovasculareventsincludingmyocardialinfarctionandstroke,which may increase

withdoseordurationofuse.Patientswithcardiovasculardiseaseorcardiovascularriskfactorsmay

alsobeatgreaterrisk.

Patientswithpreviousmyocardialinfarction(withinthelast6to

12months)shouldnotusediclofenac.

TreatmentwithVoltarenisgenerally notrecommended in patients with establishedcardiovascular

disease(e.g.congestiveheartfailure,establishedischaemicheartdisease, peripheralarterialdisease)

or uncontrolled hypertension. If needed, patients with established cardiovascular disease,

uncontrolled hypertension or significant risk factors for cardiovascular disease (e.g. hypertension,



hyperlipidemia, diabetes mellitus and smoking) should be treated with Voltaren only after  careful

considerationandonlyatdoses≤100mgdailywhentreatmentcontinuesformorethan4weeks.

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Asthecardiovascularrisksofdiclofenac mayincreasewithdoseanddurationofexposure,thelowest

effectivedailydoseshouldbeusedfortheshortestdurationpossible(seesection4.2).Thepatient's

needfor symptomatic relief andresponsetotherapy should be reevaluated periodically, especially 

when

treatmentcontinuesformorethan4weeks.

Prescribers should inform the individual patient of the possible increased risk when prescribing

diclofenacforpatientsathighriskofcardiovascularevents.

Physicians and patients should remain alert for such events, even in the absence of previous

cardiovascular symptoms. Patients should be informed

about the signs and/or symptoms of 

cardiovasculartoxicityandthestepstotakeshouldtheyoccur.Patientsshouldremainalertforthe

signs and symptoms of serious arteriothrombotic events (e.g. chest pain, shortness of breath,

weakness,slurringofspeech),whichcanoccurwithoutwarning.Patientsshouldbeinstructedtosee

physicianimmediatelyincaseofsuchanevent.

Thereisnoconsistentevidencethattheconcurrentuseofaspirinmitigatesthepossibleincreasedrisk

ofseriouscardiovascularthromboticeventsassociatedwithNSAIDuse.

Hypertension

NSAIDs may lead to the onset of new hypertension or worsening of pre‐existing hypertension and

patients taking anti‐hypertensives with NSAIDs may have an impaired anti‐hypertensive response. 

Cautionis advisedwhenprescribingNSAIDstopatientswithhypertension.Bloodpressureshouldbe

monitoredcloselyduringinitiationofNSAIDtreatmentandatregularintervalsthereafter.

Heartfailure

Fluidretentionandoedemahavebeenobservedinsomepatients

takingNSAIDs,thereforecautionis

advisedinpatientswithfluidretentionorheartfailure.

Gastrointestinaleffects

Gastrointestinalbleeding,ulcerationorperforation,whichmayincreasewithdoseordurationofuse

andwhichcanbefatal,havebeenreportedwithallNSAIDs,includingdiclofenac,andmayoccurat

any time during

treatment, with or without warning symptoms or a previous history of serious

gastrointestinal events. They generally have more serious consequences in the elderly. If

gastrointestinalbleedingorulcerationoccurinpatientsreceivingVoltaren,thetreatmentshouldbe

discontinued.

UpperGIulcers,grossbleedingorperforationcausedbyNSAIDsoccurinapproximately

1%ofpatients

treatedfor3‐6monthsand in about 2‐4% ofpatients treatedforoneyear.Thesetrends continue

withlongerdurationofuse,increasingthelikelihoodofdevelopingaseriousGIeventatsometime

duringthecourseoftherapy.However,evenshort‐termtherapyis

notwithoutrisk.

Cautionisadvisedinpatientswithriskfactorsforgastrointesti naleventswhomaybeatgreaterrisk

of developing serious gastrointestinal events, e.g. the elderly, those with a history of serious

gastrointestinalevents,smokingandalcoholism.

AswithallNSAIDs,includingdiclofenac,closemedicalsurveillanceisimperativeand

particula rcaution 

should be exercised when prescribing Voltaren in patients with symptoms indicative of

gastrointestinal(GI)disordersorwithahistorysuggestiveofgastricorintestinalulceration,bleeding

orperforation(seesection4.8).TheriskofGIbleedingishigherwithincreasingNSAIDdosesandin

patientswithahistory

oful cer, particularlyifcomplicatedwithhaemorrhageorperforationandinthe

elderly.

To reduce the risk of  GI toxicityin patients with a history of ulcer, particularly if complicated with

haemorrhageorperforation,andintheelderly,thetreatmentshouldbeinitiatedandmaintainedat 

thelowesteffectivedose.

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Combinationtherapywithprotectiveagents(e.g.protonpumpinhibitorsormisoprostol)shouldbe

consideredforthesepatients,andalsoforpatientsrequiringconcomitantuseofmedicinalproducts

containing low‐dose acetylsalicylic acid (ASA)/aspirin or other medicinal products likely to increase

gastrointestinalrisk.

Patients with a history

 of GItoxicity, particularly the elderly, should report any unusual abdominal

symptoms (especially GI bleeding). Caution is recommended in patients receiving concomitant

medicationswhichcouldincreasetheriskofulcerationorbleeding,suchas systemiccorticosteroids,

anticoagulants,anti‐plateletagentsorselectiveserotonin‐reuptakeinhibitors(seesection4.5).

Closemedical

surveillanceandcautionshouldalsobeexercisedinpatientswithulcerativecolitisor

Crohn’sdisease,astheirconditionmaybeexacerbated(seesection4.8).

TheconcurrentuseofaspirinandNSAIDsalsoincreasestheriskofseriousgastrointestinaladverse

events.

NSAIDs,includingdiclofenac,maybeassociatedwithincreasedriskofgastro

‐intestinalanastomotic

leak.ClosemedicalsurveillanceandcautionarerecommendedwhenusingVoltarenaftergastro‐

intestinalsurgery.

Doctorsshouldwarnpatientsaboutthesignsandsymptomsofseriousgastrointestinaltoxicity.

Severeskinreactions

Seriousskinreactions,someofthemfatal,includingexfoliativeder matitis,Stevens‐Johnsonsyndrome 

(SJS) and toxic epidermal

necrolysis (TEN) and Drug Reaction with Eosinophilia with

SystemicSymptoms(DRESS)(seeDrugReactionwithEosinophiliawithSystemicSymptoms(DRESS)),

havebeenreportedveryrarelyinassociationwiththeuseofNSAIDs,includingVoltaren(seesection

4.8).Theseseriousadverseeventsareidiosyncraticandareindependentofdoseordurationofuse.



Patientsappeartobeathighestriskofthesereactionsearlyinthecourseoftherapy,theonsetofthe

reaction occurring in the majority of cases within the first month of treatment. Patients shouldbe

advisedof the signs and symptoms ofseriousskinreactionsand to consult their

doctorat the first

appearanceofskinrash,mucosallesionsoranyothersignofhypersensitivity,andVoltarenshouldbe

discontinued.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also

occurinrarecaseswithdiclofenac,withoutearlierexposuretothedrug.

The sodium metabisulphite in the solution for

 injection can also lead to isolated severe

hypersensitivityreactionsandbronchospasm.

Drugreactionwitheosino philiaandsystemicsymptoms(DRESS)syndrome

DRESSsyndromehasbeenreportedinpatientstaking NSAIDs.Someoftheseeventshavebeenfatal

or life‐threatening. DRESS syndrome typically, although not exclusively, presents with fever, rash,

lymphadenopathy,

and/or facial sw elling. Other clinical manifestations may include hepatitis,

nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS

syndromemayresembleanacuteviralinfection.Eosinophiliaisoftenpresent.Becausethisdisorder

isvariableinitspresentation,otherorgansystemsnotnotedheremaybeinvolved.Itisimportantto



notethatearlymanifestationsofhypersensitivity, suchasfeverorlymphadenopathy,maybepresent

eventhough rashis notevident.Ifsuchsigns orsymptoms arepresent,discontinuethe NSAIDand

evaluatethepatientimmediately.

Maskingsignsofinfections

Like other NSAIDs, Voltaren may mask the signs and symptoms of

infection due to its

pharmacodynamicproperties.

Pre‐existingasthma

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In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps),

chronic obstructive pulmonary diseases or chronic infections of the respiratory tract (especially if

linked to alle rgic rhinitis‐like symptoms), reactions on NSAIDs like asthma exacerbations  (so‐called

intolerancetoanalgesics/analgesics‐asthma),

Quincke’soedemaorurticariaaremorefrequentthan

in other patients. Theref ore,  special precaution is recommended in such patients (read iness for

emergency).Thisisapplicableaswellforpatientswhoareallergictoothersubstances,e.g.withskin

reactions,pruritusorurticaria.

SpecialcautionisrecommendedwhenVoltarenis used

parenterallyinpatientswithbronchialasthma

becausesymptomsmaybeexacerbated.

Hepaticeffects

Close medical surveillance is required when prescribing Voltaren  to patien ts with impaire d hepatic

function,astheirconditionmaybeexacerbated.

AswithotherNSAIDs,includingdiclofenac,valuesofoneormoreliverenzymesmayincrease.During

prolonged treatment

 with Voltaren, regular moni toring of hepatic function is indicated as a

precautionarymeasure.Ifabnormalliverfunctiontestspersistorworsen,ifclinicalsignsorsymptoms

consistent with liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash),

Voltaren should be discontinued. Hepatitis may occur with use of diclofenac

without prodromal

symptoms.

CautioniscalledforwhenusingVoltareninpatientswithhepaticporphyria, sinceitmaytriggeran

attack.

Renaleffects

As fluid retention and oedema  have been reported in association with NSAID therapy, including 

diclofenac,particularcautioniscalledforinpatientswithimpairedcardiacorrenalfunction,

history

of hypertension, the elderly, patients receiving concomitant treatment with diuretics or medicinal

products that can significantly  impact renal function, and in those  patients with substantial

extracellularvolumedepletion  fromanycause,e.g.beforeorafter majorsurgery (seesection4.3).

Monitoringofrenalfunctionisrecommendedasaprecautionary

measurewhenusingVoltareninsuch

cases.Discontinuationoftherapyisusuallyfollowedbyrecoverytothepre‐treatmentstate.

Injectionsitereactions

Injection site reactions have been reported after the administration of Voltaren intramuscularly,

includinginjectionsite necrosisandemboliacutismedicamentosa,alsoknownasNicolauSyndrome

(particularly after inadvertent

 subcutaneous administration).  Appropriate needle selection and 

injectiontechniqueshouldbe followedduringi.m.administrationofVoltaren(seesection6.7Special

precautionsfordisposalandhandling)

Haematologicaleffects

During prolonged treatment with Voltaren, as with other NSAIDs, monitoring of the blood count is

recommended.

Like other NSAIDs, Voltaren may temporarily inhibit

platelet aggregation. Patients with defects of

haemostasisshouldbecarefullymonito red.

Geriatricpatients

Cautionisindicatedintheelderlyonba sicmedicalgrounds.Inparticular,itisrecommendedthatthe

lowesteffective dosebeusedin frailelderlypatientsorthose withalowbody weight (see section

4.2).

Interactionswith

otherNSAIDs

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TheconcomitantuseofVoltarenwithsystemicNSAIDsincludingcyclooxygenase‐2 selective inhibitors,

should be avoided due to the absenceof any evidence demonstrating synergistic benefits and the

potentialforadditiveundesirableeffects(seesection4.5). 



4.5 Interactionwithothermedicinesandotherformsofinteraction

Thefollowing interactions include thoseobservedwithVoltarensolutionforinjectionand/orother

pharmaceuticalformsofdiclofenac.

Observedinteractionstobeconsidered

CYP2C9 inhibitors: Caution is recommended when co‐prescribing diclofenac with potent CYP2C9

inhibitors(suchassulfinpyrazoneandvoriconazole),whichcouldresultinasignificantincreaseinpeak

plasmaconcentrations

andexposuretodiclofenacduetoinhibitionofdiclofenacmetabolism.

Lithium:Ifusedconcomitantly,diclofenacmayraiseplasmaconcentrationsoflithium.Monitoringof

theserumlithiumlevelisrecommended.

Digoxin:Ifusedconcomitantly,diclofenacmayraiseplasmaconcentrationsofdigoxin.Monitoringof

theserumdigoxinlevelisrecommended.

Diuretics and

antihypertensive agents: Like other  NSAIDs, concomitant use of diclofenac with

diuretics or antihypertensive agents (e.g. beta‐blockers, angiotensin converting enzyme (ACE)

inhibitors)maycauseadecreaseintheirantihypertensiveeffect.Therefore,thecombinationshould

be administeredwith caution and patients, especially the elderly should have their blood pressure

periodicallymonitored.Patients

shouldbeadequatelyhydratedandconsiderationshouldbegivento

monitoring of renal function after initiation of concomitant therapy and periodically thereafter,

particularlyfordiureticsandACEinhibitorsduetotheincreased riskofnephrotoxicity.(seesection

4.4).

Other NSAIDs and cortic osteroids: Concomitant administration of diclofenac and other systemic

NSAIDs

or corticosteroids may increase the frequency of gastrointestinal undesirable effects (see

section4.4).

Anticoagulantsandanti‐plateletagents:Cautionisrecommendedsinceconcomitantadministration

couldincreasetheriskofbleeding(seesection4.4).Althoughclinicalinvestigationsdonota ppearto

indicatethatdiclofenacaffectstheactionofanticoagulants,therearereports

ofanincreasedriskof

haemorrhageinpatientsreceivingdiclofenacandanticoagulantsconcomitantly.Closemonitoringof

suchpatientsisthereforere commended.

Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of systemic NSAIDs,

includingdiclofenac, andSSRIsmayincreasetheriskofgastrointestinalbleeding(seesection4.4).

Antidiabetics:Clinicalstudieshaveshown

thatdiclofenaccanbegiventogetherwithoralantidiabetic

agents without influencing their clinical effect. However, there have been isolated reports of both

hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage of the antidiabetic

agents durin g treatment with diclofenac. For this reason, monitoring of the blood glucose level is

recommended

asaprecautionarymeasureduringconcomitanttherapy.

Therehavealsobeenisolatedreportsof metabolicacidosiswhendi clofenacwasco‐administeredwith

metformin,especiallyinpatientswithpre‐existingrenalimpairment.

Methotrexate: Caution is recommended when NSAIDs, including diclofenac, are administered less

than 24 hours before or after treatment with

methotrexate, since blood concentrations of

methotrexatemayriseandthetoxicityofthissubstancebeincreased.

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Cyclosporin and Tacrolimus: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of

cyclosporinandtacrolimusduetotheeffectonrenalprostaglandins.Therefore,itshouldbegivenat

doseslowerthanthosethatwouldbeusedinpatientsnotreceivingcyclosporinandtacrolimus.

Drugs known to

 cause hyperkalemia: Concomitant treatment with potassium‐sparing diuretics,

ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium levels,

whichshouldthereforebemonitoredfrequently(seesection4.4)

Quinoloneantibacterials:Therehavebeenisolatedreportsofconvulsionswhichmayhavebeendue

toconcomitantuseofquinolonesandNSAIDs.

Phenytoin: When using phenytoin concomitantly with diclofenac, monitorin g of phenytoin plasma 

concentrationsisrecommendedduetoanexpectedincreaseinexposuretophenytoin.

CYP2C9 inducers: Caution is recommended when co‐prescribing diclofenac with CYP2C9 indu cers

(suchasrifampicin),whichcouldresultinasignificantdecreaseinplasmaconcentrationandexposure

diclofenac.



4.6 Fertility,pregnancyandlactation

UseinPregnancy

RiskSummary

Thereareinsufficientdataontheuseofdiclofenacinpregnantwomen.Someepidemiologicalstudies

suggest an increased risk of miscarriage after use of a prostaglandin synthesis inhibitor (such as

NSAIDs)inearlypregnancy,howevertheoveralldataareinconclusive.

Diclofenac has been shown to cross

 the placental barrier in humans. Use of NSAIDs, including

diclofenac,cancauseuterineinertia,prematureclosureofthefetalductusarteriosusandfetalrenal

impairmentleadingtooligohydramnios.

Becauseoftheserisks,Voltarenshouldnotbeusedduringthefirsttwotrimestersofpregnancyunless

theexpectedbenefitstothe

motheroutweightheriskstothefoetus.

Inaddition,Voltarenshouldnotbeusedduringthethirdtrimesterofpregnancy(seesection4.3).

PrematureClosureofFetalDuctusArteriosus

As with  other NSAIDs, use of diclofenac during the third trimester of pregnancy is contraindicate d

owingtothepossibilityofprematureclosure

ofthefetalductusarteriosus(seesection4.3).

Humandata

Publishedliteraturereportsthattheuseof NSAIDsduringthethirdtrimesterofpregnancymaycause

prematureclosureofthefetalductusarteriosus

Oligohydramnios/FetalRenalImpairment

Risk of fetal renal impairment with subsequent oligohydramnios has been observed when NSAIDs

(including

diclofenac)wereusedfromthe20thweekofpregnancyonwards.

IfanNSAID isnecessaryfromthe20thweekgestationtotheendofthe2ndtrimester,limittheuse

tothelowesteffectivedoseandshortestdurationpossible.IfVoltarentreatmentextendsbeyond48

hours, consider monitoring  with ultrasound for

 oligohydramnios. If oligohydramnios occurs,

discontinueVoltarenandfollowupaccordingtoclinicalpractice.

Humandata

Published studies and post‐marketing reports describe maternal NSAID use at about 20 weeks

gestation or later in  pregnancy associated with fetal renal impairment leading to oligohydramnios.

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These adverse outcomes are seen, on average, after days to weeks of treatment, although

oligohydramnioshasbeeninfre quentlyreportedassoonas48hoursafterNSAIDinitiation.Inmany

cases,butnotall,thedecreaseinamnioticfluidwastransientandreversible with cessation of the

drug.

LabourorDelivery

TherearenostudiesontheeffectsofVoltarenduringlabourordelivery.AswithotherNSAIDs,useof

diclofenacduringthethirdtrimesterofpregnancyiscontraindicatedowingtothepossibilityofuterine

inertia(seesection4.3).

Breastfeeding

LikeotherNSAIDs,diclofenacpassesintothe

breastmilkinsmallamounts.Therefore,Voltarenshould

notbeadministeredduringbreastfeedinginordertoavoidundesirableeffectsintheinfant.

Humandata

Diclofenac was detected in a low concentration (100 ng/mL) in breast milk in one nursing mother

treated orally with a diclofenac salt of 150 mg/day. The

 estimated dose ingested by an infant

consumingbreastmilkisequivalentto0.03mg/kg/day.

Fertility

Femalefertility

As with other NSAIDs, the use of Voltaren may impair female fertility and is not recommended in

women attempting to conceive. Inwomen who have difficultiesconceivingor who are  un dergoing

investigationof

infertility,withdrawalofVoltarenshouldbeconsidered.

Malefertility

ThereisnohumandataontheeffectofVoltarenonmalefertility.



4.7 Effectsonabilitytodriveandusemachines

Patientswho experiencevisualdisturbances,dizziness,vertigo,somnolence,centralnervoussystem

disturbances, drowsiness, or fatigue while taking NSAIDs should refrain from driving or operating

machinery.



4.8 Undesirableeffects

Adversedrugreactionsfromclinicaltrialsand/orspontaneousorliteraturereports(Table1) arelisted

byMedDRAsystemorganclass.Withineachsystemorganclass,theadversedrugreactionsareranked

byfrequency,withthemostfrequen treactionsfirst.Withineachfrequencygrouping,adversedrug

reactionsarepresentedinorderof

decreasing seriousness.Inaddition,thecorrespondingfrequency

category for each adverse drug reaction is based on the following convention (CIOMS III): very

common (>1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000,

<1/1,000);veryrare(<1/10,000).



ThefollowingundesirableeffectsincludethosereportedwithVoltarensolutionfor

injectionand/or

otherpharmaceuticalformsofdiclofenac,witheithershort‐termorlong‐termuse.



Table1. Adversedrugreactions

Infectionsandinfestations

Veryrare: Injectionsiteabscess

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Bloodandlymphaticsystemdisorders

Veryrare: Thrombocytopenia,leukopenia,anaemia(includinghaemolyticandaplastic

anaemia),agranulocytosis.

Immunesystemdisorders

Rare: Hypersensitivity,anaphylacticandanaphylactoidreactions(including

hypotensionandshock).

Veryrare: Angioedema(includingfaceoedema).

Psychiatricdisorders

Veryrare: Disorientation,depression,insomnia,nightmare,irritability,psychotic

disorder.

Nervoussystemdisorders

Common: Headache,dizziness.

Rare: Somnolence.

Veryrare: Paraesthesia,memoryimpairment,convulsion,anxiety,tremor,meningitis

aseptic,dysgeusia,cerebrovascularaccident.

Eyedisorders

Veryrare: Visualimpairment,blurredvision,diplopia.

Earandlabyrinthdisorders

Common: Vertigo.

Veryrare: Tinnitus,impairedhearing

Cardiacdisorders

Uncommon*:

Frequencyunknown:

Myocardialinfarction,cardiacfailure,palpitations,chestpain.

Kounissyndrome

Vasculardisorders

Veryrare: Hypertension,vasculitis.

Respiratory,thoracicandmediastinaldisorders

Rare: Asthma(includingdyspnoea).

Veryrare: Pneumonitis.

Gastrointestinaldisorders

Common Nausea,vomiting,diarrhoea,dyspepsia,abdominalpain,flatulence,anorexia.

Rare: Gastritis,gastrointestinalhaemorrhage,haematemesis,melaena,

haemorrhagicdiarrhoea,gastrointestinalulcer(withorwithoutbleeding

gastrointestinalstenosisorperforationwhichmayleadtoperitonitis).

Veryrare: Colitis(includinghaemorrhagiccolitis,ischemiccolitisandexacerbationof

ulcerativecolitisorCrohn’sdisease),constipation,

stomatitis,glossitis,

oesophagealdisorder,intestinaldiaphragmdisease,pancreatitis,

haemorrhoidsaggravated.

Hepatobiliarydisorders

 Common: Transaminasesincreased.

 Rare: Hepatitis,jaundice,liverdisorder.

 Veryrare: Fulminanthepatitis,hepaticnecrosis,hepaticfailure.

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Skinandsubcutaneoustissuedisorders

 Common: Rash.

 Rare: Urticaria.

 Veryrare: Bullousdermatitis,eczema,erythema,erythemamultiforme,Stevens‐Johnson

syndrome,toxicepidermalnecrolysis(Lyell’ssyndrome),exfoliative

dermatitis,alopecia,photosensitivityreaction,allergicpurpura,Henoch‐

Schonleinpurpura,pruritus.

 Unknown Drugreactionwitheosinophiliawithsystemicsymptoms(DRESS)

Renalandurinarydisorders

 Veryrare: Acutekidneyinjury(acuterenalfailure),haematuria,proteinuria,nephrotic

syndrome,tubulointerstitialnephritis,renalpapillarynecrosis.

Generaldisordersandadministrationsiteconditions

 Common: Injectionsitereaction,injectionsitepain,injectionsiteinduration

 Rare: Oedema,injectionsitenecrosis

*Thefrequencyreflectsdatafromlong‐termtreatmentwithahighdose(150mg/day)

Adversedrugreactionsfrompost‐marketingexperience(frequencynotknown)

Thefollowingadversedrugreactionhasbeenderivedfrompost‐marketingexperiencewithVoltaren.

Becausethisreactionwasreportedvoluntarilyfromapopulationofuncertainsize,itisnotpossible

toreliablyestimateitsfrequencywhichisthereforecategorizedasnot

known.



Table2Adversedrugreactionderivedfrompost‐marketingexperience(frequencynotknown)

Injectionsitereactions



Emboliacutismedicamentosa(Nicolausyndrome)



Descriptionofselectedadversereactions

Arteriothromboticevents

Meta‐analysis and pharmacoepidemiological data point towards a small increased risk of

arteriothromboticevents (forexamplemyocardialinfarction)associatedwith  theuse  ofdiclofenac,

particularlyatahighdose(150mgdaily)andduringlong‐termtreatment(seesection4.4).

Visualeffects

Visual

disturbances such as visual impairment,  blurred vision or diplopia appear to be NSAID class

effectsandareusuallyreversibleondiscontinuation.Alikelymechanismforthevisualdisturbancesis

the inhibition of prostaglandin synthesis  and other related compounds that alter the regulation of

retinalbloodflowresultinginpotentialchangesin

vision.Ifsuchsymptomsoccurduringdiclofenac

treatment,anophthalmologicalexaminationmaybeconsideredtoexcludeothercauses.

Reportingofsuspectedadversereactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continuedmonitoringofthebenefit/riskbalanceofthemedicine.Healthcareprofessionalsareasked

toreportanysuspectedadversereactionshttps://nzphvc.otago.ac.nz/reporting/.



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4.9 Overdose

Symptoms

There is no typical clinical picture resulting from  diclofenac overdosage. Overdosage can cause

symptoms such as vomiting, gastrointestinal haemorrhage, diarrhoea, dizziness, tinnitus or

convulsions.Intheeventofsignificantpoisoning,acuterenalfailureandliverdamagearepossible.

Therapeuticmeasures

ManagementofacutepoisoningwithNSAIDs,includingdiclofenac,essentiallyconsists

ofsupportive

measuresandsymptomatictreatment.Supportive measuresandsymptomatictreatmentshouldbe

givenforcomplicationssuchashypotension,renalfailure,convulsions,gastrointestinaldisorder, and

respiratorydepression.

Special measures such as forced diuresis, dialysis or haemoperfusion are probably of no help in

eliminatingNSAIDs,includingdiclofena c,duetothehigh

proteinbindingandextensivemetabolism.

For advice on the management of overdose please contact the National Poisons Centre on 0800

POISON(0800764766).

5 PHARMACOLOGICALPROPERTIES

5.1 Pharmacodynamicproperties

Pharmacotherapeuticgroup:anti‐inflammatoryandantirheumaticproducts,non‐steroids,aceticacid

derivativesandrelatedsubstances(ATCcode:M01AB05).

Mechanismofaction

Voltarencontainsdiclofena csodium,anon‐steroidalcompoundwithpronouncedantirheumatic,anti‐

inflammatory, analgesic, and antipyretic properties. Inhibition of prostaglandin biosynthesis, which

has been demonstrated in experiments, is considered

 fundamental to its mechanism  of action.

Prostaglandinsplayamajorroleincausinginflammation,pain,andfever.

Diclofenacsodiuminvitrodoesnot suppressproteoglycanbiosynthesisincartilageatcon centrations

equivalenttothosereachedinhumans.

Pharmacodynamiceffects

In rheumatic diseases, the anti‐inflammatory and analgesic properties of Voltaren elicit

a clinical

response characterised by marked relief from signs and symptoms such as  pain at rest, pain on

movement,morningstiffness,andswellingofthejoints, aswellas byanimprovementinfunction.

Voltarenhasalso beenfoundtoexertapronouncedanalgesiceffectinmoderateandseverepainof



non‐rheumaticorigin,aneffectwhichsetsinwithin15to30minutes.

Voltarenhasalsobeenshowntohaveabeneficialeffectinmigraineattacks.

In post‐traumatic and post‐operative inflammatory conditions, Voltaren rapidly relieves both

spontaneouspainandpainonmovementandreducesinflammatoryswellingandwound

oedema.

When used  concomitantly with opioi ds  for the management of post‐operative pain, Voltaren

significantlyreducestheneedforopioids.

Voltaren ampoules are particularly suitable for initialtreatment of inflammatory and degenerative

rheumaticdiseases,andofpainfulconditionsduetoinflammationofnon‐rheumaticorigin.

5.2 Pharmacokineticproperties

Absorption

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Afteradministrationof75mgdiclofenacbyintramuscularinjection,absorptionsetsinimmediately,

andmeanpeakplasmaconcentrationsofabout2.5micrograms/mL(8micromol/L)arereachedafter

about20mi nutes.When75mgdiclofenacisadministeredasanintravenousinfusionover2hours,

meanpeakplasma

concentrationsare about1.9micrograms/mL(5.9micromol/L).Shorterinfusions

result in higher peak plasma concentrations, while longer infusions give plateau concentrations

proportionaltotheinfusionrateafter3to4hours.Incontrast,plasmaconcentrationsdeclinerapidly

once peak levels have been reached following intramuscular injection or administration of gastro‐

resistanttabletsorsuppositories.

The area under the concentration curve(AUC) after intramuscular or intravenous  administration is

about twice as  large as it is following oral or rectal administration, because about half the active

substance is metabolised during its first passage through the liver ("first pass" effect) when

administeredviathe

oralorrectalroutes.

Pharmacokineticbehaviourdoesnotchangeafterrepeatedadministration.Noaccumulationoccurs

providedtherecommendeddosageintervalsareobserved.

Distribution

99.7%ofdiclofenacisboundtoserumproteins,mainlytoalbumin99.4% ).Theapparentvolumeof

distributioncalculatedis0.12to0.17L/kg.

Diclofenacentersthesynovial

fluid,wheremaximum concentrationsaremeasured2to4hoursafter

peakplasmavalueshavebeenattained.Theapparenthalf‐lifeforeliminationfromthesynovialfluid

is3to6hour s.Twohoursafterreachingpeakplasmavalues,concentrationsoftheactivesubstance

arealreadyhigherinthesynovialfluid

thanintheplasma,andtheyremainhigherforupto12hours.

Diclofenacwasdetectedinalowconcentration(100ng/mL )inbreastmilkinonenursingmother.The

estimated amount ingested by an infant consuming breast mil k is equivalent to a 0.03 mg/kg/day

dose.

Metabolism

Biotransformation of diclofenac

takes place partly by glucuronidation of the intact molecule, but

mainly by single and multiple hydro xylation and methoxylation, resulting in several phenolic

metabolites (3’‐hydroxy‐,4’‐hydroxy‐,5‐hydroxy‐,4’,5‐dihydroxy‐ and 3’‐hydroxy‐4’‐methoxy‐

diclofenac), most of which are  converted to glucuronide conjugates. Two of these phenolic

metabolitesare

biologicallyactive,buttoamuchsmallerextentthandiclofenac.

Elimination

Totalsystemicclearanceofdiclofenacfr omplasmais 263±56mL/min(meanvalue±SD).Theterminal 

half‐lifein plasmais1to2hours.Four ofthemetabolites,includingthetwo activeones,alsohave

shortplasma

half‐livesof1to3hours.Onemetabolite,3’‐hydroxy‐4’‐methoxy‐diclofenachasamuch

longerplasmahalf‐life.However,thismetaboliteisvirtuallyinactive.

About60%oftheadministereddoseisexcretedintheurineastheglucuronideconjugateoftheintact

moleculeandasmetabolites,mostof

whicharealsoconvertedtoglucuronideconjugates.Lessthan

1%isexcretedasunchangedsubstance.Therestofthedoseiseliminatedasmetabolitesthroughthe

bileinthefaeces.

Linearity/non‐linearity

Theamountabsorbedisinlinearproportiontothesizeofthedose.

Pharmacokineticsinspecialpatientgroups

Norelevantage‐dependentdifferencesinthedrug’sabsorption,metabolism,orexcretionhavebeen

observed.However,inafewelderlypatientsa15‐minuteintravenousinfusionresultedin50%higher

plasmaconcentrationsthanexpectedfromthedataonyounghealthysubjects.

NEWZEALANDDATASHEET

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Inpatientssufferingfromrenalimpairment,noaccumulationoftheunchangedactivesubstancecan

beinferredfr om the single‐dose kinetics when applying theusualdosageschedule.Atacreatinine

clearance of <10 mL/min, thecalculated steady‐state plasma levels of the hy droxymetabolitesare

about

 4 times higher than in normal subjects. However, the metabolites are ultimately cleared

throughthebile.

In patients with chronic hepatitis or non‐decompensated cirrhos is, the kinetics and metabolism of

diclofenacarethesameasinpatientswithoutliverdisease.

5.3 Preclinicalsafetydata

Preclinical data from acute and repeated dose toxicity studies, as well as from genotoxicity,

mutagenicity,andcarcinogenicitystudieswithdiclofenacrevealednospecifichazardforhumansat

theintendedtherapeuticdoses.

Oligohydramnios/FetalRenalImpairment

Reproductive and developmental  studies in animals demonstrated that diclofenac administration 

duringorganogenesisdidnotproduce teratogenicity despite

theinduction ofmaternaltoxicityand

fetaltoxicityinmiceatoraldosesupto20mg/kg/day(0.41timesthemaximumrecommendedhuman

dose[MRHD]ofVoltaren,200mg/day,basedonbodysurfacearea(BSA)comparison),andinratsand

rabbitsatoraldosesupto10mg/kg/day(0.41and

0.81times,respectively,theMRHDbasedonBSA

comparison).

In a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (0.08 and 0.16

timestheMRHDbasedonBSA)fromGestationDay15throughLactationDay21,significantmaternal

mortality (caused by gastrointestinal ulceration and peritonitis) was

 noted. These maternally toxic

doses were associated with dystocia, prolonged gestation, intrauterine growth retardation, and

decreasedfetalsurvival.

AdministrationofNSAIDs(includingdiclofenac)inhibitedovulationintherabbitandimplantationand

placentationintherat,andledtoprematureclosureofthefetalductusarteriosus.

LabourorDelivery

In animal

studies, NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed

parturition,andincreasetheincidenceofstillbirth.

Fertility

Diclofenacadministeredtomaleandfemaleratsat4mg/kg/day(approximately0.16timestheMRHD

basedonBSAcomparison)didnotaffectfertility.



6 PHARMACEUTICALPARTICULARS

6.1 Listofexcipients

Mannitol;sodiummetabisulphite(E223);benzylalcohol;propyleneglycol;waterforinjection;sodium 

hydroxide;nitrogen,pure.

Informationmightdifferinsomecountries.



6.2 Incompatibilities

Asarule,Voltarensolutionforinjectionshouldnotbemixedwithotherinjectionsolutions.

NEWZEALANDDATASHEET

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Infusionsolutionsofsodiumchloride0.9%orglucose5%withoutsodiumbicarbonateasanadditive

present a risk of supersaturation, possibly leading to formation of crystals or precipitates. Infusion

solutionsotherthanthoserecommendedshouldnotbeused.



6.3 Shelflife

2years.



6.4 Specialprecautionsforstorage

Storebelow30°C.

Storeintheoriginalpackageinordertoprotectfromlight.



6.5 Natureandcontentsofcontainer

Colourlessglassampoulesof3mLinpacksof5.



6.6 Specialprecautionsfordisposalandhandling

Thefollowingdirectionsforintramuscularinjection mustbefollowedinordertoavoiddamagetoa

nerveorothertissueattheinjectionsite.

To be injected either intramuscularly by deep intragluteal injection into the upper outer quadrant

using aseptic technique, or intravenously by slow infusion after dilution in accordance with

 the

followinginstructions.Eac hampouleisforsingleuseonly.Thesolutionshouldbeusedimmediately

afteropening.Anyunusedcontentsshouldbediscarded.

Appropriateinjectiontechniqueandlengthoftheneedle(consideringthethicknessofthepatient’s

glutealfat)shouldbeusedtoavoidinadvertentsubcutaneousadministrationofVoltaren

injection.

Dependingontheintendeddurationofinfusion(seeDosageofadministration),mix100to500mLof

isotonic saline (sodium chloride 0.9 % solution) or glucose 5 % solution buffered with sodium

bicarbonate injectable solution (0.5 mL of 8.4 % or 1 mL of 4.2 % or a corresponding volume

 of a

different concentration) taken from a freshly opened container; add the contents of one Voltaren

ampouletothissolution.Onlyclearsolutionsshouldbeused.Ifcrystalsorprecipitatesareobserved,

theinfusionsolutionshouldnotbeused.

7 MEDICINESCHEDULE

Prescriptionmedicine

8 SPONSOR

NovartisNewZealandLimited

POBox99102

Newmarket

Auckland1149

NewZealand

Telephone:0800354335

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®=RegisteredTrademark

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NEWZEALANDDATASHEET



 Page16of16

9 DATEOFFIRSTAPPROVAL

21May1980

10 DATEOFREVISIONOFTHETEXT

07March2023



SUMMARYTABLEOFCHANGES

Sectionchanged Summaryofnewinformation

4.4Specialwarnings

andprecautionsforuse

AddedtextaboutDrugReactionwithEosinophiliawithSystemic

Symptoms(DRESS)

4.8Adverseeffects AddedDRESStoTable1Adversedrugreactions



Internaldocumentcode:vli170323iNZbasedonCDSv3.0dated8September2 022