NEW ZEALAND MEDICINESAND MEDICAL DEVICESSAFETY AUTHORITY

A BUSINESS UNIT OFTHE MINISTRY OF HEALTH

www.medsafe.govt.nz

A publication of

Prescriber UpdateVol. 33 No. 1March 2012

ISSN 1172-5648

Prescriber Update is a member of the

A publication of

Antithrombotic Medicines – Still Causing Bleeding 1

Preventing Medication Errors: Tacrolimus Case Study 1

Nicobrevin – Do the Benefits Outweigh the Risks? 2

Citalopram and Escitalopram – Similar Risk of QT Prolongation? 3

Aqueous Cream – Moisturiser or Irritant? 4

Complementary Corner: St John’s Wort and Serotonin Syndrome 4

Seasonal Flu Vaccine – Spontaneous Reporting in 2011 5

Reminder: Depression and Suicidality Can Occur with Interferon Use 6

Adverse Reaction Reporting in New Zealand in 2011 7

IMMP Update: Varenicline (Champix) Monitoring 9

MARC’s Remarks: December Meeting 10

MEDICINES MONITORING: New Medicine Added 10

1 Prescriber Update 2012; 33(1) March

Early treatment of bleeds is desirable and patients and/or carers should be advised to monitor for early signs of bleeding.

Key Messages

• Amajorriskfactorforbleedsistheuseofmore than one antithrombotic medicine.

• Patientsand/orcarersshouldbeadvisedtomonitor for the early signs of bleeding.

References1. A New Zealand Consensus Forum. 2011. The use of

antithrombotic medicines in general practice: a consensus statement. Best Practice Journal,39:10-21

Preventing Medication Errors: Tacrolimus Case Study

New formulations of existing medicines cansometimescauseconfusion,especiallywhenthereis a change to dosing frequency.

Thisarticledrawsprescribers’attentiontothenewprolonged-releaseformulationoftacrolimusthatisnowapprovedforuseinNewZealand.

Antithrombotic Medicines – Still Causing Bleeding

Ant i coagu l an t s and an t i p l a t e l e t agen t s(antithrombotics) are widely used to treat anumber of conditions, with recent guidanceon their use being issued by the Best PracticeAdvocacyCentre(BPAC)1.

Bleeding is themajor risk associated with allantithrombotics.TheCentreforAdverseReactionMonitoring(CARM)continuestoreceivereportsofseriousbleedsexperiencedbypatientstakingthese medicines.

Anoverviewof12monthsofreportingtoCARMis shown inTable 1.Themain sites of seriousbleeding were most often gastrointestinal orintracranial in origin.

Only a small fraction of suspected adverse reactions are reported to CARM, neverthelessthese reports show that seriousbleedsdooccurwithantithromboticsand that somebleedsmayhave been preventable. For example, althoughcombination therapy is recommended for some conditions, adverse reaction data continues to indicate amajor risk factor for bleeding is theconcomitant use of more than one antithrombotic medicine.

Table 1: Antithrombotic CARM reports associated with bleeding from 1 Oct 2010 to 30 Sept 2011.

Medicine Total number of reports

Number of reports of bleeding

(%)

Number of bleeding cases reported to be exposed to another anticoagulant or antiplatelet agent

(%)

Number of bleeding cases reported to also be exposed to a NSAID or SSRI

(%)

Aspirin 28 68 53 42

Clopidogrel 9 67 100 16

Dabigatran* 212 42 59 3

Dipyridamole 3 67 100 50

Enoxaparin 14 50 57 0

Rivaroxaban 3 0 N/A N/A

Warfarin 32 56 50 11*Dabigatranhasbeenrecentlyintroducedwithrapiduptake

Prescriber Update 2012; 33(1) March 2

TacrolimusiscurrentlymarketedasPrografandthenewformulationasPrografXL.Importantly,tacrolimus has a narrow therapeutic indexand medication errors have the potential to significantly harm patients.

Prograf

• Is an immediate release formulation intended for twice daily dosing.

Prograf XL

• Is a prolonged release formulat ion intended for once daily dosing.

ThemanufacturerofPrografandPrografXLhasemployedanumberofmethodstoreducetheriskofconfusionbetweenthetwobrands,suchas:

• colourcodingofthecapsulesandblisters,withdistinctive colouring for immediate versus prolonged release capsules

• theuseofpackingoverwraptohighlighttheXLformulationandpatientdosingcards

• the use of shelf talkers for pharmacies toreducethepotentialforpickingerrors.

In addition, themanufacturer is attempting tointroduce warning flags on prescribing anddispensingsoftware.

International experience

Cases of medication errors, due to confusionover tacrolimus formulations, have already been reportedinothercountries.Insomecases,theseerrors resulted in serious adverse reactions, includingrejectionoftransplantedorgans1.

Errors have occurred at the prescribing, dispensing and administration of tacrolimus.

References1. Medicines and Healthcare Products RegulatoryAgency.

2010.Oral tacrolimus products:measures to reduce risk ofmedication errors. Drug Safety Update,3(10):5

Key Messages• Toreducethepotentialforerror,tacrolimus

shouldbeprescribedwithafulldescriptionof the drug, the formulation (immediate release or prolonged release), the strength and frequency of dosing.

• Prescribersshouldalsoconsideraddingthebrand name to prescriptions.

• Pharmacistsshouldcontacttheprescriberif the strength, brand or formulation is not absolutely clear.

• Switchingbetweenformulationsorbrandsof tacrolimus requires careful medical supervision and may require therapeutic monitoringandre-titration.

• Patients should be advised to familiarisethemselveswiththenameandappearanceof their tacrolimusmedication and checkwith their doctor or pharmacist if theyhave any concerns about the medicine they receive.

Nicobrevin – Do the Benefits Outweigh the Risks?

Following thewithdrawal ofNicobrevin in theUnitedKingdom,Medsaferequestedareviewofthebenefitsandrisksof thismedicinefromtheproductsponsor.TheMedicinesAdverseReactionCommittee (MARC) reviewed this informationalong with information about the individualingredientscontainedinNicobrevin.

Nicobrevinisusedasanaidtoquittingsmokingand contains: menthyl valerate, camphor, quinine andeucalyptusoil.Theseingredientsareclaimedtohelptorelievethesymptomsassociatedwithstoppingsmoking.

TheMARCconsideredthatstudiesreviewedinsupport of the efficacy ofNicobrevin providedlittle evidence of benefit. Studies reviewedincludedtheDankwaetal.studyconductedin92smokersin1988andarecentlyupdatedCochranereview1,2.

3 Prescriber Update 2012; 33(1) March

However, despite the paucity of evidence ofefficacy in the scientific literature, theMARCnoted that even if this product only had a placebo effect this might still be helpful in enabling smokerstoquit.

TherewaslittleevidenceoffrequentseriousharmoccurringwiththeuseofNicobrevin,althoughthefollowingwasnoted:

• valerianmayimpairdrivingability;thisriskextendstoallproductscontainingvalerian3

• valeriancancausegastrointestinalreactions3

• quinine, even at a low dose, can causethrombocytopenia and hypersensit ivity reactionsinrarecases;thisriskalsoextendstotonicwater4,5.

TheMARCconcludedthattherewasinsufficientevidence demonstrating serious harm to justifyremoving the product from the New Zealandmarket.

To providemore information for patients andminimisetheriskofadverseeffects,theMARCrecommendedthattheNicobrevinpackagelabelandpackageinsertbeupdatedtoreflecttheriskofadversereactions.Medsafeisworkingwiththesponsor to update the label.

References1. DankwaE,PerryL,PerkinsA.1988.Adouble-blind,placebo-

controlledstudytodeterminetheefficacyofNicobrevinanti-smokingcapsules.British Journal of Clinical Practice,42(9):359-363.

2. SteadLF,LancasterT.2006.Nicobrevinforsmokingcessation.Cochrane Database of Systematic Reviews,Issue2,Art.No.CD005990.DOI:10.1002/14651858.CD005990.

3. European MedicinesAgency. 2006. Community herbalmonograph on Valeriana officinalisL.,radix.Doc.ref.EMEA/HMPC/340719/2005. URL:www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2009/12/WC500017925.pdf

4. Brasic JR. 2001. Quinine-induced thrombocytopenia in a64-year-oldmanwhoconsumedtonicwatertorelievenocturnalleg cramps. Mayo Clinic Proceedings,76(8):863-864

5. BelB, JeudyG,BouillyD, et al. 2009.Fixederuptiondueto quinine contained in tonicwater: positive patch testing.Contact Dermatitis,61(4):242-244

Citalopram and Escitalopram – Similar Risk of QT Prolongation?

Citalopram and Escitalopram are selectiveserotoninreuptakeinhibitors(SSRIs)usedforthetreatment of depressive illness.

Arecentclinical study found thatcitalopram isassociatedwithadosedependentincreaseintheriskofQTprolongation1.QTprolongationisanestablished side effect of Class I andClass IIIantiarrhythmic medicines and a rare side effect of a wide range of other medicines that leadto cardiac dysrhythmia. Formore informationaboutdrug-inducedQTprolongationrefertothearticlepublishedintheDecember2010editionofPrescriber Update2.

The New Zealand data sheets for citalopramhave been updated to describe the risk ofQT prolongation, contraindicate its use inpatientswithcongenital longQTsyndromeandrecommendanewmaximumdoseof40mgdaily.Information on prescribing citalopram safelyhasrecentlybeenpublishedbytheBestPracticeAdvocacyCentre(BPAC)3.

Toassessifthisriskextendedtoescitalopram,asecondclinicalstudywasconducted4.ThestudydeterminedthatescitalopramwasassociatedwithsubstantiallylessQTprolongationthancitalopramandwasonlyseenatsupratherapeuticdoses(30mg daily). In New Zealand the recommendeddoseis10mgoncedaily,whichcanbeincreasedtoamaximumof20mgdailydependingonthepatient’sresponse4-6.

Al though o the r SSRIs a r e ava i l ab l e i n NewZealand,therelativeriskofQTprolongationassociatedwiththeuseofthesemedicinesisnotyet clearly defined. Medsafe is in the process of reviewingthisriskforallSSRIsandwillprovidefurtherinformationwhenitisavailable.

Prescribersareremindedtoconsidertherisksandbenefits of SSRI treatment, particularly beforeprescribing inpatientswithcongenital longQTsyndromeorthosewithmultipleriskfactors.

Prescribers are advised to seek specialistcardiological and/or psychiatric advice if necessary.

Prescriber Update 2012; 33(1) March 4

Key Messages• CitalopramisassociatedwithariskofQT

prolongation at therapeutic doses.

• EscitalopramisassociatedwithanincreasedriskofQTprolongationatsupratherapeuticdoses.

• Citalopram and escitalopram should beusedwithcautioninpatientswithmultipleriskfactorsforQTprolongation.

References1. Food and DrugAdministration. 2011.Abnormal heart

rhythms associatedwith high doses of Celexa (citalopramhydrobromide). Drug Safety Communication,24August2011

2. Medsafe.2010.Drug-inducedQTprolongationandTorsadesdePointes–thefacts.Prescriber Update,31(4):27-29

3. BestPracticeAdvocacyCentre.2012.Prescribingcitalopramsafely: an update. Best Practice Journal,42:38-41

4. HealthcareLogistics.2011.Lexapro data sheet

5. MylanNewZealandLtd.2011.Loxalate data sheet

6. ApotexNZLtd.2011.Apo-Escitalopram data sheet

Aqueous Cream – Moisturiser or Irritant?

Aqueous cream is themost widely prescribedemollientforthetreatmentofdryskinconditionsand is often the first line of treatment for patients with eczema1. However, recent studies suggestthat the use of aqueous cream can damage the skinbarrierwhenusedasaleave-onemollient1-3.

AqueouscreamBPfirstappeared in theBritishPharmacopoeia in 1958 and the formulationhas remained unchanged since then. One of its ingredients, sodium lauryl sulphate, is an emulsifierandknownskinirritant.Althoughtheproduct was originally intended to be a washproduct,itisnowgenerallyprescribedandusedasbothasoapsubstituteandleave-onemollient1.

Users of aqueous cream have reported high rates ofskinirritation,promptingtheNationalInstituteforHealthandClinicalExcellence(NICE)intheUnited Kingdom to remove it from their guideline onthemanagementofeczemain2007.

Eczemaarisesfromacombinationofgeneticandenvironmentalfactorsleadingtothebreakdownoftheskinbarrier.Soapandsurfactants,suchas

sodium lauryl sulphate, have been identified as negative environmental factors and their use is notrecommendedinpatientswitheczema.

Newresearch,publishedintheBritish Journal of Dermatology,showsthataqueouscreaminducesskin irritation2.Thestudycomparedparametersof skin barrier function between skin treatedwithaqueouscreamasaleave-onemollientanduntreatedskin.Treatedareasshowedadecreaseinthesizeandmaturityofkeratinocytes,causingtheskin’sprotectivestructuretobecompromised.Treatedskinalsoshowedincreasedtransepidermalwaterloss,reflectingimpairedbarrierfunction.

In patients with a history of atopic dermatitisaqueous cream appeared to cause a greater amount of skinbarrierdamageand subjective irritationwascommon3.

Thesepapershighlighttheimportanceofnotusingproducts containing sodium lauryl sulphate, such asaqueouscream,asleave-onemollientsastheymay act to exacerbate skin damage rather thansupportskinbarrierfunction.

References1. TangM,GuyRH.2010.EffectofAqueousCreamBPonhuman

stratum corneum in vivo. British Journal of Dermatology, 163(5):954-958

2. MohammedD,MattsPJ,HadgraftJ,etal.2011.InfluenceofAqueousCreamBPoncorneocytesize,maturity,skinproteaseactivity,proteincontentandtransepidermalwaterloss.British Journal of Dermatology,164(6):1304-1310

3. DanbySG,Al-EneziT,SultanA, et al. 2011.The effect ofaqueous cream BP on the skin barrier in volunteers witha previous history of atopic dermatitis. British Journal of Dermatology,165(2):329-334

Complementary Corner: St John’s Wort and Serotonin Syndrome

A single cup of Healtheries “Be Happy” teaand two days of citalopram treatment has beenassociated with a case of serotonin syndromeresulting in hospitalisation.

The report received by the Centre forAdverseReactionsMonitoring(CARM)describesapatientwho was started on low dose citalopram oneday after ingesting “BeHappy” tea.After justtwo doses of citalopram, the patient developedsymptoms consistent withmoderate serotoninsyndrome1.

5 Prescriber Update 2012; 33(1) March

“BeHappy” tea lists820mgofSt John’sWortper tea bag.

StJohn’swortisaherbalsubstancefromtheplantStJohn’swort(Hypericum perforatum).StJohn’swort is traditionally used for the treatment ofdepressionandrelatedconditionssuchasanxiety,tiredness, loss of appetite and trouble sleeping.

StJohn’swortisknowntointeractwithselectiveserotoninreuptakeinhibitors(SSRIs),inthesamewayasserotonergicdrugssuchastramadolandcitalopram, by further increasing the serotonin level in the brain2. The concomitant use of StJohn’swortandSSRIsisnotrecommendedandisincludedasaninteractioninSSRIdatasheets2.

Adverse reactions from interactionswith othermedicines could happenwith any product thatcontains a large amount H. perforatum.Furtherinformation about clinically important interactions ofSt John’swort canbe found in theFebruary2001editionofPrescriber Update3.

Healthcare professionals are encouraged to askpatients about their use of complementary and alternative medicines and to report all suspected adversereactionstoCARM.

References1. Medsafe. 2010. Serotonin syndrome/toxicity - reminder.

Prescriber Update,31(4):30-31

2. European MedicinesAgency. 2009. Community herbalmonograph on Hypericum perforatumL.,herba(well-establishedmedicinaluse).Doc.Ref.EMA/HMPC/101304/2008.URL:www.emea.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2010/01/WC500059145.pdf

3. Medsafe.2001.InteractionswithStJohn’swort(Hypericum perforatum) preparations. Prescriber Update,20:42-48

Seasonal Flu Vaccine – Spontaneous Reporting in 2011

The Centre forAdverse ReactionsMonitoring(CARM) and Medsafe thank everyone whocontributed to the monitoring of the flu vaccine last season by reporting suspected adverse reactions.

In 2011, approximately 200 reports of adverseevents suspected to be related to influenzavaccination were received by CARM. Thiscompareswithover400reportsreceivedin2010,

whenconcernswereraisedaboutcasesoffeversand febrile convulsions in children.

The funded vaccines in 2011 were Fluvaxand Fluarix. Fluarix was recommended by theMinistry of Health for eligible children under nine years of age.

Use in Children

In 2011, there was only one report of febrileconvulsions suspected to be associated withinfluenza vaccine (Vaxigrip). There were fourreports of death coincident with influenzaimmunisation in2011.CARMdidnot considerany of these reports to be caused by the vaccine.

Feverwas reported in nine children, includingone child less than nine years of age whoreceived Fluvax. There was one report of analmost immediate allergic reaction (including urticariaandperiorbitaloedema).Thechildwasappropriately treated and recovered withoutsequelae.

Guillain-Barré Syndrome

There were two instances of patients in their70’s experiencing Guillain-Barré syndromefollowing immunisation.However, informationabout possible confounding factors, such as prior infections,wasnotprovided.

Epidemiological studies have not consistently found an association between Guillain-Barrésyndrome and influenza vaccines, with thereportingratefortheseeventsremaininglowerthanthebackgroundrateinthegeneralpopulation1-3.

Conclusions

After an analysis of repor ts received in New Zealand in 2011, CARM considered thenature of reports was as expected for vaccinerelated adverse events.

Next Season

The strains of influenza to be used in nextseason’s(2012)vaccinewillremainunchanged,asdothePHARMACfundedbrands(FluvaxandFluarix).For eligible childrenunder nineyearsofage,Fluarixcontinuestobetherecommendedinfluenzavaccine.

Prescriber Update 2012; 33(1) March 6

References 1. Haber P, Sejvar J,MikaeloffY, et al. 2009.Vaccines and

Guillain-Barrésyndrome.Drug Safety,32(4):309-323

2. Stowe J,AndrewsN,Wise L, et al. 2006.Bell’s palsy andparenteral inactivated influenza vaccine.Human Vaccines, 2(3):110-112

3. Black S, Eskola J, Siegrist CA, et al. 2009. Importance ofbackgroundratesofdiseaseinassessmentofvaccinesafetyduringmass immunisationwith pandemicH1N1 influenzavaccines. Lancet,374(9707):2115-2122

Reminder: Depression and Suicidality Can Occur With Interferon Use

Prescribers are reminded that depression and/or suicidal ideation are commonly reported side effects of interferon alpha therapy and have also beenreportedwithinterferonbetause1,2.

Prescribers should also be aware that patientswith chronic hepatitisC infection andmultiplesclerosis (MS) have a high background risk ofpsychiatric disorders such as depression.

Interferonsarenaturallyoccurringcytokineswithantiviralandimmunomodulatoryproperties.Thethreemajor interferon classes (alpha, beta andgamma) have overlapping but distinct biological activities.

InterferonalphaisindicatedforthetreatmentofchronichepatitisBandCinfection,haematologicalmalignancies(e.g.hairycellleukaemia,chronicmyelogenous leukemia,multiplemyeloma andnon-Hodgkin’slymphoma)andKaposi’ssarcoma.Interferonbeta is indicated for the treatmentofMS.

The Centre forAdverse ReactionMonitoring(CARM) has received six reports of suicidalideation/tendency and three reports of death by suicide, associated with the use of interferonalpha. This includes three patients takingpegylated interferon plus ribavirin.

IndicationsforusewerehepatitisC(5),chronicmyelogenousleukemia(1)andunknown(3).Thedurationtoonsetofsymptomsrangedfromtwoweeksto11months(average4.8months).Oftheninepatients,fivepatientshadotherriskfactorsforsuicidalideationincludinghepatitisCinfection(5), intravenous drug use (1) concomitant ribavirin (2)andco-existingdepression(4).

Possible activation symptoms (e.g. agitation,anxiety, aggression and irritability) were alsoexperienced by six patients. The extent ofadditionalpsychosocialfactorswasnotreported.

CARMhasalso receivedone reportof suicidalideationwith interferon beta (in a patientwithMS).

Key Advice for Healthcare Professionals1,3

• Patientsshouldbescreenedforpsychiatricsymptoms prior to interferon treatment.

• Interferonshouldbeusedwithcautionandpsychiatricreviewshouldbeconsideredinpatientswithcurrentdepressionorahistoryof depression.

• Mood and suicidal ideation should bemonitored closely during interferon therapy.

• Patientsshouldbeadvisedtoseekmedicaladvice immediately i f symptoms of depression or suicidal ideation occur or worsenduringinterferontreatment.

• Specialist advice should be sought ifdepression and/or suicidal ideation do notimprovewithtreatment.Thepotentialbenefit of ongoing interferon treatment should be weighed carefully against therisksofworseningdepression.

References1. SockalingamS,Links PS,AbbeySE. 2011. Suicide risk in

hepatitisCandduringinterferon-alphatherapy:areviewandclinical update. Journal of Viral Hepatitis,18(3):153-160

2. GoebJL,EvenC,NicolasG,etal.2006.Psychiatricsideeffectsofinterferon-betainmultiplesclerosis.European Psychiatry, 21(3):186-193

3. Roche Products (New Zealand) Limited. 2011.Pegasys data sheet

Note: PHARMAC fully subsidises interferon alpha (Pegasys, Pegasys RBV, Intron A and Roferon A) u n d e r s p e c i a l a u t h o r i t y f o r t h e t re a t m e n t o f chronic hepatitis B and C infection and interferon beta (Avonex and Betaferon) for the t reatment of MS.

7 Prescriber Update 2012; 33(1) March

Adverse Reaction Reporting in New Zealand in 2011

Allmedicineshaverisksandbenefits.

Before a med ic ine i s r e l eased in to the New Zealand market, safety and efficacyexperienceislimitedtoitsuseinclinicaltrials.Some important reactionsmaynot be observeduntil a large number of people have received the medicineorhave takenthemedicinefora longperiod.Continuedmonitoringofadversereactionsis therefore essential.

National adverse reactions reporting activities(spontaneous reporting) in New Zealand arecoordinated by Medsafe and the Centre forAdverseReactionsMonitoring(CARM).

Healthcare professionals (and consumers) can report a suspected adverse reaction to medicines (including vaccines) and complementary therapies (CAMs)bysubmittingareportthroughoneofthefollowingmethods:

1. completingayellowcardsentviafreeposttoCARM

2. downloadinga formfromeither theCARMorMedsafewebsites

3. completing an online report available from eithertheCARMorMedsafewebsites

4. electronicreportingthroughGPsoftware

5. Prescriber Update form

6. iPhoneapp.

These reports are subsequently analysed toidentify possible safety signals that require further investigation. Possible safety signalsmay appear on the scheme (medsafe.govt.nz/profs/M2MedicinesMonitoring.asp) and/or further action may be taken. Informationabout pharmacovigilance in New Zealand isavailable at www.medsafe.govt.nz/Consumers/Safety-of-Medicines/Medicines-Safety-and-Pharmacovigilance.asp.

In2011,CARMreceivedatotalof4331suspectedadverse reaction reports.This number includessuspected adverse reactions to medicines, vaccines and CAMs. The number of reportssubmitted has remained consistent for the past fouryears(Figure1).

Themajorityof the reports receivedbyCARMin2011wereassociatedwithmedicines(66.5%)(Figure2).Vaccinescontributedto33.1%oftotalsuspectedadversereports,withCAMsmakinguptheremaining0.4%.Thisisasimilarbreakdownwhencompared to the reports received in2010(Figure2).

Reports to CAMs remain low with only 19submitted in 2011. Possible factors that couldexplain the low numbers of reports include:adverse reactions to CAMs are rare, adversereactionstoCAMsarenotwellrecognisedoralackofawarenessthatadversereactionstoCAMscanbereportedtoCARM.

Figure 1: Adverse reaction reports submitted to CARM from 2006 to 2011.

2006 2007 2008 2009 2010 2011

5000

4000

3000

2000

1000

0

2892

2830

4447 46424140 4331

Year

Tota

l N

umbe

r of

Rep

orts

Prescriber Update 2012; 33(1) March 8

Figure 3: Source of adverse reaction reports from Healthcare Professional in New Zealand in 2011.

4%4%

1%

27%

14%

6%6%

38%

Other

Public

Other Healthcare Professionals

Nurse

Community Pharmacist

Hospital Pharmacist

Hospital Doctor

General Practitioner

Examination of the suspected adverse reactionreportsreceivedin2011showed21.7%oftotalreportswereconsideredtobeserious.Aseriousadverse reaction is determined by CARMaccording to internationally agreed criteria i.e. resulting in hospitalisation, life-threatening,fatal, results in a disability, requires intervention to prevent permanent disability or results in a congenital abnormality.

80

70

60

50

40

30

20

10

0

58

41

32

68

21

7974

26

63

36

1 0.7 0.4 0.3 0.3

2006 2007 2008 2009 2010 2011

Medicines

Vaccines

CAMs

0.4

33

66

Figure 2: Types of adverse reaction reports from 2006 to 2011.

Year

Per

cent

age

of T

otal

Rep

orts

Approximately one third of reports relating tomedicineswereconsideredseriousand10.5%ofCAMreportsreceivedbyCARMwereconsideredserious (Table 1). Interestingly, only 4.3% ofvaccinereportssubmittedweredeemedserious.

Thesourceofadversereactionreportsreceivedin2011isshowninFigure3.In2011,themajorityofadverse reaction reports submitted by healthcare professionalscamefromnurses,followedbyGPsthenhospitaldoctors(Figure3).

9 Prescriber Update 2012; 33(1) March

Table 1: Types of adverse reactions reports for 2011.

Type Serious (%)

Non-serious (%)

Medicines 30.5 69.5

Vaccines 4.3 95.7

CAMs 10.5 89.5

MedsafeandCARMwouldliketothankallthosewho have contributed to pharmacovigilance in NewZealandbysubmittingreportsofsuspectedadverse reactions and encourage continued supportfor2012.

Adverse reaction reporting provides valuableinformation about the use of medicines in clinical practice and is a vital part of pharmacovigilance inNewZealand.

Further information about adverse reactionsand how to submi t an adverse reac t ionreport can be found on theMedsafe website, www.medsafe.govt.nz,orontheCARMwebsite, www.otago.ac.nz/carm.

IMMP Update: Varenicline (Champix) Monitoring

Thevareniclinepost-marketmonitoringprojectwas contracted byMedsafe to the IntensiveMedicinesMonitoringProgramme(IMMP).

Sincemonitoringbeganin2007,thevareniclinepatientcohorthasnowreacheditspre-specifiedcohortsizeandnowcontainsover12,000patients.

AnumberofimportantinterimfindingshavebeenpublishedbasedondatafromtheIMMPincluding:

• informationabouttheutilizationofvareniclinein New Zealand, including identificationthat some patients were not receiving therecommended12weeksoftreatment1

• analyses of the frequency of psychiatricadverse events2,3

• a case series of cardiovascular events inpatientstakingvarenicline4

• acaseseriesofpatientsdescribingepistaxisand other bleeding eventswhile taking thismedicine5.

Finalanalysisofthevareniclinedatacollectedinthismonitoringprojectisexpectedinmid-2012andwill be summarised in a future edition ofPrescriber Update.

TheIMMPhasinformedMedsafethatvareniclinequestionnaireswillcontinuetobesentoutafter30 June 2012. Please continue to return anyoutstanding questionnaires to the IMMP in theusualway.

Thank you to all healthcare professionalswhohaveparticipatedinthismonitoringprojectandhave provided valuable information about the safety and use of varenicline.

IMMPmethodology can be used to investigatemany d i ffe ren t medic ine sa fe ty i s sues . OrganisationsareabletocontractIMMPstudiestoanswertheirresearchquestions.

Healthcare professionalswill be alerted to anynewpost-marketmonitoringprojectsastheyareidentified and initiated.

References1. Harrison-WoolrychML,Ashton J. 2010.Utilization of the

smoking cessationmedicine varenicline: an intensive post-marketingstudyinNewZealand.Pharmacoepidemiology and Drug Safety,19(9):949-953

2. Harrison-WoolrychML.2009.Vareniclineandsuicide:safetydatafromNewZealand.British Medical Journal, 339: b5654. DOI:10.1136/bmj.b5654

3. Harrison-WoolrychML,AshtonJ.2011.Psychiatricadverseeventsassociatedwithvarenicline:anintensivepostmarketingprospectivecohortstudyinNewZealand.Drug Safety, 34(9): 763-772.

4. Harrison-WoolrychML,Maggo S, TanM, et al. 2012.Cardiovascularevents inpatients takingvarenicline:acaseseries from intensive postmarketing surveillance in NewZealand.Drug Safety,35(1):33-43

5. Harrison-WoolrychML, Harmark L, TanM, et al. 2012.Epistaxisandotherhaemorrhagiceventsassociatedwiththesmokingcessationmedicinevarenicline:acaseseries fromtwonationalpharmacovigilancecentres.European Journal of Clinical Pharmacology.DOI:10.1007/s00228-012-1220-y.

Prescriber Update 2012; 33(1) March 10

NEW ZEALAND MEDICINESAND MEDICAL DEVICESSAFETY AUTHORITY

A BUSINESS UNIT OFTHE MINISTRY OF HEALTH

www.medsafe.govt.nz

A publication of

NEW ZEALAND MEDICINESAND MEDICAL DEVICESSAFETY AUTHORITY

A BUSINESS UNIT OFTHE MINISTRY OF HEALTH

www.medsafe.govt.nz

A publication of

NEW ZEALAND MEDICINESAND MEDICAL DEVICESSAFETY AUTHORITY

A BUSINESS UNIT OFTHE MINISTRY OF HEALTH

www.medsafe.govt.nz

A publication of

NEW ZEALAND MEDICINESAND MEDICAL DEVICESSAFETY AUTHORITY

A BUSINESS UNIT OFTHE MINISTRY OF HEALTH

www.medsafe.govt.nz

A publication of

MEDICINES MONITORINGWE NEED yOUR hElP!

Please send your reports for these potential safety issues* listed in the table below.

Medicine Potential safety issue Active monitoring ends

ENDING SOONLansoprazole, Pantoprazole

Hypomagnesaemia 31 March 2012

ExTENDEDSildenafil Thromboembolism 30 September 2012

NEWCetirizine Severe Mood Disorder 30 September 2012

• The scheme does not replace rout ine adverse react ion report ing. Find out how to report at: http://www.otago.ac.nz/carm or http://www.medsafe.govt.nz

Reporting form for Adverse Reactionsto Medicines, Vaccines and Devices

and all Clinical Events for IMMP

Surname: First Name/s:

Address:

ALL MEDICINES IN USE *ASTERISK SUSPECT MEDICINE/S* Include over-the-counter (OTC) and alternative medicines

Medicine or Vaccine+batch no. Daily Dose Route Date Started Date Stopped Reason for Use (and brand name if known)

DESCRIPTION OF ADVERSE REACTION OR EVENT

Date of onset:

Recovered Not yet recovered but improved Not yet recovered Unknown Fatal - Date of Death:

Severe? - Yes No Rechallenged? - No Yes Result:

OTHER FACTORS - Please tick or specify as appropriate

Renal disease Allergy : Other Medical Conditions:

Hepatic disease Nutritional Suppl or OTC use : Industrial Chemicals :

REPORTER - Please tick as appropriate: Doctor Pharmacist Dentist Nurse Other :

Name:

Address: Signature:

Phone: Date:

Send completed form to CARMFreepost 112002, CARM, PO Box 913, Dunedin 9054 or Fax: (03) 479 7150

NHI No:

Date of Birth:

Ethnicity:

PATIENT DETAILS HP3442

Fax: (03) 479 7150Phone: (03) 479 7247

Sex:* The appearance of a possible safety issue in this scheme does not mean Medsafe and CARM have concluded that this medicine causes the reaction.

MARC’s Remarks: December Meeting

TheMedicinesAdverse Reactions Committee(MARC)meton8December2011andmadethefollowingrecommendations.

TheMARC was provided with an update onthe safety profile of dabigatran (Praxada).TheCommitteewasadvisedthat,comparedwiththefirst fewweeksof funding,only two reportsofmedication error were received by the CentreofAdverse ReactionMonitoring (CARM) inOctober. TheMARC were satisfied that thenumber of medication errors associated withdabigatran treatment is decreasing and agreed that thebalanceofbenefitsandrisksremainspositiveat present.

TheMARC reviewed the benefits and risks ofNicobrevin following its withdrawal from theUnitedKingdom.Refertothearticleinthiseditionof the Prescriber Update1.

TheMARCwasprovidedwithacomparisonofusage data and spontaneous reports involving tramadolbeforeandoneyearfollowingfundingofArrow-Tramadol50mgcapsulesbyPHARMAC.TheCommittee acknowledged that the adverseeventreportsreceivedsincetramadolwasfundedhave been similar in nature and proportion to those received prior to funding.

Further information relating to these mattersis available from theMARCmeetingminutespublishedontheMedsafewebsite:

w w w. m e d s a f e . g o v t . n z / p r o f s / a d v e r s e /Minutes148.htm

References1. Medsafe.2012.Nicobrevin–benefitriskreview.Prescriber

Update,33(1):2-3

Prescriber Update is published and distributed by Medsafe in the interests of safer, more effective use of medicines and medical devices.

Medsafe: NewZealandMedicinesandMedicalDevicesSafetyAuthority AbusinessunitoftheMinistryofHealth

Editor: ChrisJames,BPharmDPH Medsafe,POBox5013,Wellington6145,NewZealand Ph:(04)8196800Fax:(04)8196806 E-mail:Chris_James@moh.govt.nz

Editorial Team: DrAmandaTaylor,PhD SeniorAdvisorPharmacovigilance JanCarey AdvisorScience DrMartinBonne MedicalAdvisor DrRichardJaine SeniorMedicalAdvisor DrSharonSime SeniorMedicalAdvisor DrSusanKenyon,PhD SeniorAdvisorPharmacovigilance

Principal Clinical Advisor: DrEnverYousuf

Group Manager: DrStewartJessamine

Medsafe also acknowledges the contribution of the New Zealand Pharmacovigilance Centre in providing data and advice for articles

An electronic version of Prescriber Update is available at www.medsafe.govt.nz/profs/PUarticles.asp

To receive Prescriber Update electronically, please register at www.medsafe.govt.nz/profs/profs.asp

Data sheets, consumer medicine information, media releases, medicine classification issues and adverse reaction forms can be found at

www.medsafe.govt.nz

Published with the permission of the Director-General of Health

The copyright owner of this publication is the Ministry of Health, which is part of the New Zealand Crown. Information about copyright

requirements available at www.moh.govt.nz/copyright